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Dose-Escalated Hypofractionated Adaptive Radiotherapy for Head and Neck Cancer (DEHART)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04477759
Recruitment Status : Recruiting
First Posted : July 20, 2020
Last Update Posted : April 25, 2022
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Musaddiq Awan, Medical College of Wisconsin

Brief Summary:

Locoregional failure remains the principal mode of mortality in head and neck squamous cell carcinoma (HNSCC) treated with conventional chemoradiation therapy. Magnetic resonance-guided radiation therapy (MRgRT) allows for adaptive radiation dose escalation based on tumor response and may improve therapeutic outcomes while limiting toxicities.

This protocol evaluates a novel framework for radiation delivery with concurrent atezolizumab in patients with advanced HNSCC. Dose-Escalated Hypofractionated Adaptive Radiotherapy (DEHART) modifies radiation dose using MRgRT by escalating radiation dose to residual tumor while deescalating radiation dose to areas of tumor regression.


Condition or disease Intervention/treatment Phase
Head and Neck Neoplasm Radiation: 50 Gy Radiation Therapy Radiation: 55 Gy Radiation Therapy Radiation: 60 Gy Radiation Therapy Drug: Atezolizumab Phase 1

Detailed Description:

Locoregional failure remains the principal mode of mortality in head and neck squamous cell carcinoma (HNSCC) treated with conventional chemoradiation therapy. Radiation dose escalation with hypofractionation has shown unparalleled local control in other malignancies, such as non-small cell lung cancer, but has been limited in HNSCC due to toxicity concerns. Magnetic resonance-guided radiation therapy (MRgRT) allows for adaptive radiation dose escalation based on tumor response and may improve therapeutic outcomes while limiting toxicities.

This protocol evaluates a novel framework for radiation delivery using MRgRT with concurrent atezolizumab in patients with advanced HNSCC. Unlike conventional radiotherapy, Dose-Escalated Hypofractionated Adaptive Radiotherapy (DEHART) modifies radiation dose using MRgRT by adapting the radiation plan during the course of treatment, escalating radiation dose to residual tumor while deescalating radiation dose to areas of tumor regression. The hypothesis is that DEHART will safely deliver ablative radiation doses in 15 fractions over 3 weeks while limiting both toxicity and the effect of tumor repopulation by resistant clonogens, thus resulting in an improved therapeutic ratio.

This Phase I clinical trial will encompass the following specific aims: (1) determine the maximum tolerated dose (MTD) of the DEHART regimen delivered using MRgRT with concurrent atezolizumab in a population of patients who are not candidates or unsuitable for definitive chemoradiation therapy; (2) evaluate the toxicity and functional outcomes of the DEHART regimen; and (3) assess the efficacy of DEHART and obtain volumetric and functional imaging correlates of efficacy using MRgRT to serve as hypothesis-generating data for future trials of radiation dose adaptation. A modified Time-to Event Continual Reassessment (TITE-CRM) Phase I Design with three radiation dose levels delivered to regressing disease will be used to determine the MTD: 50 Gy in 15 fractions, 55 Gy in 15 fractions and 60 Gy in 15 fractions.

If DEHART is found to be safe and shows a signal of efficacy in this study, a future Phase II trial will be conducted to compare this novel treatment strategy to standard-of care conventionally fractionated chemoradiation in patients with locally advanced HNSCC.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: This study will use a time-to-event continual reassessment method (TITE-CRM) for assigning subjects to the radiation therapy dosages.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial of MR-Guided Dose-Escalated Hypofractionated Adaptive Radiation Therapy and Immunotherapy in Primary Metastatic or Very Locally Advanced Patients With Head and Neck Cancer
Actual Study Start Date : January 26, 2021
Estimated Primary Completion Date : August 2, 2023
Estimated Study Completion Date : August 2, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 50 Gray (Gy) Radiation Therapy
50 Gy of ionizing radiation therapy will be administered in 15 fractions.
Radiation: 50 Gy Radiation Therapy
Ionizing radiation

Drug: Atezolizumab
Atezolizumab (1,680 mg) will be given to all subjects by intravenous injection every 4 weeks following the initiation of radiation treatment up to 1 year from radiation fraction 1.
Other Name: Tecentriq

Experimental: 55 Gray (Gy) Radiation Therapy
55 Gy of ionizing radiation therapy will be administered in 15 fractions.
Radiation: 55 Gy Radiation Therapy
Ionizing radiation

Drug: Atezolizumab
Atezolizumab (1,680 mg) will be given to all subjects by intravenous injection every 4 weeks following the initiation of radiation treatment up to 1 year from radiation fraction 1.
Other Name: Tecentriq

Experimental: 60 Gray (Gy) Radiation Therapy
60 Gy of ionizing radiation therapy will be administered in 15 fractions.
Radiation: 60 Gy Radiation Therapy
Ionizing radiation

Drug: Atezolizumab
Atezolizumab (1,680 mg) will be given to all subjects by intravenous injection every 4 weeks following the initiation of radiation treatment up to 1 year from radiation fraction 1.
Other Name: Tecentriq




Primary Outcome Measures :
  1. Incidence of Dose-Limiting Toxicities [ Time Frame: 12 months ]
    This measure is the number of subjects experiencing a dose-limiting toxicity. A dose-limiting toxicity is defined as an inability to complete radiation treatment within 30 days of the start of radiotherapy that is not deemed to be related to disease progression; OR an unacceptable toxicity within one year of treatment (Grade 4+ toxicity) that is probably or definitely related to radiation treatment as determined by the treating physician or a death within one year of treatment that is probably or definitely related to treatment.

  2. Maximum Tolerated Radiation Dose [ Time Frame: 12 months ]
    This measure is the highest radiation dose at which there is a 30% or more rate of dose-limiting toxicity up to 12 months after completion of radiation treatment using the TITE-CRM design.


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 1 year ]
    This measure is the number of subjects alive at 1 year following the conclusion of scheduled radiation therapy.

  2. Locoregional progression [ Time Frame: 1 year ]
    This measure is the number of subjects showing disease progression in the head and neck by RECIST criteria.

  3. Gross Tumor Volume at Radiation Fraction 6 (Change from Baseline) [ Time Frame: 6th Radiation Fraction (approximately 1 week) ]
    This measure is the change in gross tumor volume for each subject as contoured on pre-treatment (baseline) and treatment 6 imaging scans.

  4. Gross Tumor Volume at Radiation Fraction 11 (Change from Baseline) [ Time Frame: 11th Radiation Fraction (approximately 2 weeks) ]
    This measure is the change in gross tumor volume for each subject as contoured on pre-treatment (baseline) and treatment 11 imaging scans.

  5. MD Anderson Symptom Inventory for Head and Neck (MDASI-HN) Score [ Time Frame: Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1 ]
    MD Anderson Symptom Inventory for Head and Neck tool comprises 11-item Likert-style questions assessing 9 symptoms relevant to head and neck cancer. Responses range from 0 (no 'symptom') to 10 (severe 'symptom').

  6. MD Anderson Symptom Inventory for Head and Neck Domain Score (Mucus in the Mouth and Throat) [ Time Frame: Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1 ]
    This measure is the score for the "mucus in the mouth and throat" domain items of the MD Anderson Symptom Inventory tool. The measure is derived from a subset of 11-item Likert-style questions presented in the full inventory tool that assess symptoms relevant to mucus in the mouth and throat. Responses range from 0 (no 'symptom') to 10 (severe 'symptom').

  7. MD Anderson Symptom Inventory for Head and Neck Domain Score (Difficulty Swallowing or Chewing) [ Time Frame: Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1 ]
    This measure is the score for the "difficulty swallowing or chewing" domain items of the MD Anderson Symptom Inventory tool. The measure is derived from a subset of 11-item Likert-style questions presented in the full inventory tool that assess symptoms relevant to swallowing or chewing. Responses range from 0 (no 'symptom') to 10 (severe 'symptom').

  8. MD Anderson Symptom Inventory for Head and Neck Domain Score (Choking or Coughing) [ Time Frame: Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1 ]
    This measure is the score for the "choking or coughing" domain items of the MD Anderson Symptom Inventory tool. The measure is derived from a subset of 11-item Likert-style questions presented in the full inventory tool that assess symptoms relevant to coughing or a sensation of choking. Responses range from 0 (no 'symptom') to 10 (severe 'symptom').

  9. MD Anderson Symptom Inventory for Head and Neck Domain Score (Difficulty with Voice or Speech) [ Time Frame: Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1 ]
    This measure is the score for the "difficulty with voice or speech" domain items of the MD Anderson Symptom Inventory tool. The measure is derived from a subset of 11-item Likert-style questions presented in the full inventory tool that assess symptoms relevant to voice production and quality or speech. Responses range from 0 (no 'symptom') to 10 (severe 'symptom').

  10. MD Anderson Symptom Inventory for Head and Neck Domain Score (Skin Pain, Burning or Rash) [ Time Frame: Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1 ]
    This measure is the score for the "skin pain, burning or rash" domain items of the MD Anderson Symptom Inventory tool. The measure is derived from a subset of 11-item Likert-style questions presented in the full inventory tool that assess symptoms relevant to the sensation of pain and/or burning and/or presence of a rash in irradiated areas of the skin. Responses range from 0 (no 'symptom') to 10 (severe 'symptom').

  11. MD Anderson Symptom Inventory for Head and Neck Domain Score (Constipation) [ Time Frame: Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1 ]
    This measure is the score for the "constipation" domain items of the MD Anderson Symptom Inventory tool. The measure is derived from a subset of 11-item Likert-style questions presented in the full inventory tool that assess symptoms relevant to constipation and bowel function. Responses range from 0 (no 'symptom') to 10 (severe 'symptom').

  12. MD Anderson Symptom Inventory for Head and Neck Domain Score (Problems with Tasting Food) [ Time Frame: Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1 ]
    This measure is the score for the "problems with tasting food" domain items of the MD Anderson Symptom Inventory tool. The measure is derived from a subset of 11-item Likert-style questions presented in the full inventory tool that assess symptoms relevant to the sensation of taste. Responses range from 0 (no 'symptom') to 10 (severe 'symptom').

  13. MD Anderson Symptom Inventory for Head and Neck Domain Score (Mouth or Throat Sores) [ Time Frame: Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1 ]
    This measure is the score for the "mouth or throat sores" domain items of the MD Anderson Symptom Inventory tool. The measure is derived from a subset of 11-item Likert-style questions presented in the full inventory tool that assess symptoms relevant to sores or lesions present in the mouth and throat. Responses range from 0 (no 'symptom') to 10 (severe 'symptom').

  14. MD Anderson Symptom Inventory for Head and Neck Domain Score (Problems with Teeth or Gums) [ Time Frame: Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1 ]
    This measure is the score for the "problems with teeth or gums" domain items of the MD Anderson Symptom Inventory tool. The measure is derived from a subset of 11-item Likert-style questions presented in the full inventory tool that assess symptoms relevant to oral health particularly the teeth and gums. Responses range from 0 (no 'symptom') to 10 (severe 'symptom').

  15. MD Anderson Dysphagia Inventory Global Score [ Time Frame: Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1 ]
    This measure comprises a single five-item, Likert-style question with responses ranging from 'Strongly Agree' to 'Strongly Disagree'. A higher score ('Strongly Agree') corresponds to a worse outcome.

  16. MD Anderson Dysphagia Inventory Composite Score [ Time Frame: Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1 ]
    This measure comprises 19 five-item, Likert-style questions with responses ranging from 'Strongly Agree' to 'Strongly Disagree'. Questions are worded such that higher scores ('Strongly Agree') corresponds to worse traits or more severe symptoms.

  17. MD Anderson Dysphagia Inventory Score (Emotional) [ Time Frame: Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1 ]
    This measure is the score for the "emotional" domain comprising a subset of five-item, Likert-style questions of the MD Anderson Dysphagia Inventory Composite tool that assesses symptoms relevant to emotional health. Responses range from 'Strongly Agree' to 'Strongly Disagree'. Questions are worded such that higher scores ('Strongly Agree') correspond to worse traits or more severe symptoms.

  18. MD Anderson Dysphagia Inventory Score (Functional) [ Time Frame: Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1 ]
    This measure is the score for the "functional" domain comprising a subset of five-item, Likert-style questions of the MD Anderson Dysphagia Inventory Composite tool that assesses symptoms relevant to the ability to function in daily life activities. Responses range from 'Strongly Agree' to 'Strongly Disagree'. Questions are worded such that higher scores ('Strongly Agree') correspond to worse traits or more severe symptoms.

  19. MD Anderson Dysphagia Inventory Score (Physical) [ Time Frame: Baseline; weeks 1, 2, and 3 during radiotherapy; weeks 1, 2, 3, 4 and months 3, 6, 9 and 12 following fraction 1 ]
    This measure is the score for the "physical" domain comprising a subset of five-item, Likert-style questions of the MD Anderson Dysphagia Inventory Composite tool that assesses symptoms relevant to the ability to perform physical activities. Responses range from 'Strongly Agree' to 'Strongly Disagree'. Questions are worded such that higher scores ('Strongly Agree') correspond to worse traits or more severe symptoms.

  20. Eating Assessment Tool (EAT-10) Score [ Time Frame: Baseline, and months 3 and 6 following fraction 1 ]
    The Eating Assessment Tool comprises 10 five-item, Likert-style questions querying various aspects of swallowing. Responses range from 0 (No problem) to 4 (Severe problem). The total of the responses represents the EAT-10 score. Higher numbers indicate poorer swallowing ability.

  21. Functional Oral Intake Scale (FOIS) [ Time Frame: Baseline, and months 3 and 6 following fraction 1 ]
    The Functional Oral Intake Scale is a clinician-completed ordinal rating scale ranging from 1 (No oral intake) to 7 (Total oral intake with no restrictions). Higher numbers indicate more favorable feeding capability.

  22. Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) Grade [ Time Frame: Baseline, and months 3 and 6 following fraction 1 ]
    The DIGEST grade is a five-item modified barium swallow scale for grading pharyngeal dysphagia as a toxicity endpoint. The DIGEST grade responses are: grade 1= mild, grade 2= moderate, grade 3= severe, and grade 4= life threatening pharyngeal dysphagia.



Information from the National Library of Medicine

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Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years
  • Diagnosis of T3-T4 N0-N3 M0 or T0-T4 N1-N3 M0 squamous cell carcinoma of the head and neck squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or carcinoma of unknown head/neck primary) based on American Joint Committee on Cancer guideline (AJCC; 8th edition) with measurable disease who meet at least 1 one of the following 3 criteria:

    1. Not a candidates for concurrent, bolus, cisplatin-based chemoradiation therapy based on one of the following criteria (a-e)

    1. Age ≥ 70 with moderate to severe comorbidity or vulnerability to cisplatin, defined as having one or more of the following conditions within 4 week of registration:

      1. Modified Charlson Comorbidity Index ≥ 1
      2. Adult Comorbidity Evaluation-27 (ACE-27) Index ≥ 1
      3. ω score < 0.80
      4. Geriatric 8 (G-8) score ≤ 14
      5. Cancer and Aging Research Group (CARG) Toxicity Score ≥ 30%
      6. Cumulative Illness Rating Scale-Geriatric (CIRS-G) Score ≥ 4
    2. Age < 70 with severe comorbidity or vulnerability to cisplatin, defined as having two or more of the following conditions within 4 weeks prior to registration:

      1. Modified Charlson Comorbidity Index ≥ 1
      2. ACE-27 Index ≥ 1
      3. ω score < 0.80
      4. G-8 score ≤ 14
      5. CARG Toxicity Score ≥ 30%
      6. CIRS-G Score ≥ 4
    3. Creatinine clearance < 60 cc/min by the Cockroft-Gault formula
    4. Pre-existing peripheral neuropathy
    5. Clinical need for a hearing aid or 25+ decibel shift over 2 contiguous frequencies on a pre-treatment hearing test

      2. Patient refuses concurrent cisplatin-based chemoradiation therapy

      3. Patient has recurrent disease after definitive surgical resection

  • Any patient 18 years or older with primary metastatic (AJCC 8th edition T1-T4 N0-N3 M1) squamous cell carcinoma of the head and neck
  • Zubrod performance status 0-3
  • Measurable primary and/or nodal tumor in the head and neck region at the time of radiotherapy
  • Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up.
  • Ability to tolerate multiple MRIs
  • Adequate hematologic function within 14 days prior to registration defined as follows: Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3, platelets ≥ 100,000 cells/mm^3, hemoglobin ≥ 9.0 g/dl, lymphocyte count ≥500/mL. (Note: The use of transfusion or other intervention to achieve Hgb ≥ 9.0 g/dl is acceptable).
  • Adequate hepatic function within 14 days prior to registration defined as follows: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 times institutional upper limit of normal, serum bilirubin ≤ 1.5 x institutional upper limit of normal.
  • For patients not receiving therapeutic anticoagulation: international normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
  • For patients receiving therapeutic anticoagulation: stable anticoagulant regimen.
  • Negative HIV test at screening{, with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/μL, and have an undetectable viral load}.
  • Negative hepatitis B surface antigen (HBsAg) test at screening.
  • Inclusion of Covid-19 positive patients will be based on standard institutional protocol.
  • Female patients must meet one of the following:

    • Postmenopausal for at least one year before the screening visit, or
    • Surgically sterile (i.e., undergone a hysterectomy or bilateral oophorectomy), or
    • If subject is of childbearing potential (defined as not satisfying either of the above two criteria), agree to practice two acceptable methods of contraception (combination methods require use of two of the following: diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male or female condom, hormonal contraceptive) from the time of signing of the informed consent form through 90 150 days after the last dose of study agent, AND o Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptom-thermal, post ovulation methods] and withdrawal are not acceptable contraception methods).
  • Male patients, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following:

    • Practice effective barrier contraception during the entire study period and through 150 calendar days after the last dose of study agent, OR
    • Must also adhere to the guidelines of any study-specific pregnancy prevention program, if applicable, OR o Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptom-thermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
  • Ability to understand a written informed consent document, and the willingness to sign it.

Exclusion Criteria:

  • Prior invasive malignancy within the past 3 years (except for non-melanomatous skin cancer, and early stage treated prostate cancer);
  • Life expectancy less than 12 months
  • Performance status Zubrod >3
  • Inability to encompass all gross disease in 19 cm superior to inferior planning target volume to be treated on the MR LINAC
  • MRI-incompatible foreign body
  • Claustrophobia precluding ability to tolerate multiple MRIs
  • MRI-incompatible pacemaker or implantable cardioverter defibrillator (ICD) placement
  • Patients with Cochlear implant
  • Patients with prior radiation therapy to the head and neck Note: Prior external beam radiotherapy is excluded, but Iodine 131 is allowed.
  • Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer
  • Major surgery within 28 days prior to registration
  • Body weight ≤ 30 kg
  • Any of the following severe laboratory abnormalities within 14 days of registration, unless corrected prior to it: Sodium < 130 mmol/L or > 155 mmol/L; Potassium < 3.5 mmol/L or > 6 mmol/L ;Fasting glucose < 40 mg/dl or > 400 mg/dl;Serum calcium (ionized or adjusted for albumin) < 7 mg/dl or > 12.5 mg/dl; Magnesium < 0.9 mg/dl or > 3 mg/dl
  • Unstable angina and/or congestive heart failure requiring hospitalization within 3 months prior to Step 1 registration
  • Transmural myocardial infarction within 3 months prior to Step 1 registration
  • Respiratory illness requiring hospitalization at the time of Step 1 registration
  • Note: If the respiratory illness is resolved and the patient meets the eligibility status above, then the patient can be considered for the trial.
  • Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to Step 1 registration
  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Clinically apparent jaundice and/or known coagulation defects
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion: Patients with vitiligo or alopecia; Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; Any chronic skin condition that does not require systemic therapy; Patients without active disease in the last 5 years may be included but only after consultation with the medical oncology study chair; Patients with celiac disease controlled by diet alone.
  • History of active primary immunodeficiency including, but not limited to Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition. The need to exclude patients with AIDS from this protocol is necessary because the treatment involved in this protocol may be immunosuppressive. Patients with known HIV, cluster of differentiation 4 (CD4) cell counts ≥ 200/μL, and undetectable viral loads who are stable on an antiretroviral regimen may be included.
  • Current or prior use of immunosuppressive medication within 14 days before registration, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions: Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Principal Investigator confirmation has been obtained. Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
  • Receipt of live attenuated vaccination within 30 days prior to registration
  • Medical or psychiatric illness which would compromise the patient's ability to tolerate treatment or limit compliance with study requirements
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during treatment and for 6 months after the last dose of atezolizumab, this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. Women who are breastfeeding are also excluded.
  • Prior allergic reaction or hypersensitivity to atezolizumab or any of study drug excipients.
  • History of allogenic stem cell or organ transplantation
  • Uncontrolled hypertension
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled serious chronic gastrointestinal condition associated with diarrhea
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis (TB) testing in line with local practice), hepatitis B (known positive hepatitis B viral (HBV) surface antigen (HBsAg) result), hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody (anti-HBc) and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • History of leptomeningeal disease.
  • Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) Patients with indwelling catheters (e.g., PleurXâ) are allowed.
  • Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN)
  • Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis

    • Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
    • Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
    • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:

      • Rash must cover < 10% of body surface area
      • Disease is well controlled at baseline and requires only low-potency topical corticosteroids
      • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
  • Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
  • Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
  • Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia

    o Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.

  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
  • Live, attenuated vaccines (e.g., FluMistâ) are prohibited within 4 weeks prior to initiation of study treatment, during treatment with atezolizumab, and for 5 months after the last dose of atezolizumab.
  • Current treatment with anti-viral therapy for HBV
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
  • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
  • History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
  • Known allergy or hypersensitivity to any component of the chemotherapy formulation
  • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment
  • Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04477759


Contacts
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Contact: Medical College of Wisconsin Clinical Trials Office 414-805-8900 cccto@mcw.edu

Locations
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United States, Wisconsin
Froedtert & Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Medical College of Wisconsin
Genentech, Inc.
Investigators
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Principal Investigator: Musaddiq Awan, MD Medical College of Wisconsin
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Responsible Party: Musaddiq Awan, Principal Investigator, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT04477759    
Other Study ID Numbers: PRO00038841
First Posted: July 20, 2020    Key Record Dates
Last Update Posted: April 25, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Musaddiq Awan, Medical College of Wisconsin:
Radiotherapy
Atezolizumab
Targeted Radiation Therapy
Head and Neck Cancer
Cancer
Magnetic Resonance Guided Radiation Therapy
Additional relevant MeSH terms:
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Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Atezolizumab
Antineoplastic Agents