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History of Changes for Study: NCT02608385
Study of PD1 Blockade by Pembrolizumab With Stereotactic Body Radiotherapy in Advanced Solid Tumors
Latest version (submitted March 14, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 November 16, 2015 None (earliest Version on record)
2 December 10, 2015 Recruitment Status, Study Status and Contacts/Locations
3 January 4, 2016 Contacts/Locations, Study Status and Conditions
4 July 20, 2016 Study Status
5 May 10, 2017 Recruitment Status, Study Status, Contacts/Locations and Study Design
6 January 2, 2018 Recruitment Status, Study Status, Contacts/Locations and Study Design
7 April 30, 2018 Arms and Interventions, Outcome Measures, Study Status, Study Design, Contacts/Locations, Eligibility, Conditions, Study Description and Oversight
8 October 7, 2019 Study Status
9 June 4, 2020 Recruitment Status, Study Status, Contacts/Locations and Study Design
10 February 16, 2021 Study Status
11 January 7, 2022 Study Status
12 March 14, 2022 Study Status
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Study NCT02608385
Submitted Date:  November 16, 2015 (v1)

Open or close this module Study Identification
Unique Protocol ID: IRB15-1130
Brief Title: Study of PD1 Blockade by Pembrolizumab With Stereotactic Body Radiotherapy in Advanced Solid Tumors
Official Title: Phase I Study of PD1 Blockade by Pembrolizumab With Stereotactic Body Radiotherapy in Advanced Solid Tumors
Secondary IDs:
Open or close this module Study Status
Record Verification: November 2015
Overall Status: Not yet recruiting
Study Start: December 2015
Primary Completion: December 2017 [Anticipated]
Study Completion:
First Submitted: November 9, 2015
First Submitted that
Met QC Criteria:
November 16, 2015
First Posted: November 18, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
November 16, 2015
Last Update Posted: November 18, 2015 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: University of Chicago
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary:

Objective:

To determine the recommended SBRT dose to various metastatic locations in patients with advanced solid tumors, and specifically in the lung in patients with NSCLC, in conjunction with pembrolizumab treatment.

Detailed Description:
Open or close this module Conditions
Conditions: Non-small Cell Lung Cancer
Advanced Solid Tumor
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 138 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Advanced Solid Tumor

All subjects will receive stereotactic body radiotherapy and Pembrolizumab.

Pembrolizumab will be administered as a 30 minute IV infusion every 3 weeks.

Dosage form for pembrolizumab will be a lyophilized powder for injection.

Drug: Stereotactic body radiotherapyDrug: Pembrolizumab
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Recommended stereotactic body radiotherapy (SBRT) dose in combination with pembrolizumab.
[ Time Frame: 24 Months ]

To determine the recommended SBRT dose to various metastatic locations in patients with advanced solid tumors, and specifically in the lung in patients with NSCLC, in conjunction with pembrolizumab treatment.

Each metastasis targeted with SBRT will be assigned to one of the seven "Metastasis Locations". Patients will receive 3 or 5 fractions of radiation as determined by the location of the metastases to be irradiated.

Exact logistic regression 13 analyses will be conducted to model the probability of DLT as a function of site dose, number of metastatic sites, and cumulative body radiation. These analyses will be conducted separately for each site using all patients with lesions at that site. If these analyses suggest a high (>=33%) probability of toxicity for a particular combination of predictors, dose recommendations may be modified

Secondary Outcome Measures:
1. Rate of adverse events
[ Time Frame: 6 Months ]

To estimate rates of ≥ grade 3-4 adverse events, scored according to NCI CTCAE v. 4.0, by organ system that occur within 6 months from the start of SBRT
2. Rate of long term adverse events
[ Time Frame: 6-24 Months ]

Rates of long-term adverse events, scored according to NCI CTCAE v. 4.0, after 6 months from the end of SBRT
3. Response rate
[ Time Frame: 6 Months ]

Response rates will be tabulated with 90% confidence limits based on the binomial distribution.
4. Progression-free survival
[ Time Frame: 6 months ]

Progression-free survival will be estimated using the Kaplan-Meier method.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Be willing and able to provide written informed consent/assent for the trial.
  2. Be 18 years of age on day of signing informed consent.
  3. Have a histologically confirmed advanced solid tumor for which curative treatment is not available.

    - In expansion subjects must have either renal cell carcinoma or lung cancer.

  4. Have undergone all appropriate standard of care treatment options (in the opinion of the treating investigator). Patients with NSCLC must have undergone EGFR and ALK testing and have received appropriate initial therapy.
  5. Have measurable disease based on RECIST 1.1 including at least two tumor lesions that meet criteria for SBRT radiation.
    • <65 cc of viable metastases (approximately 5cm in dimension)
    • Metastases located in lung, liver, mediastinal/cervical node, Spinal/Paraspinal, Osseous, abdominal-pelvic (lymph node/adrenal gland)
    • The two lesions must be ≥5cm apart when measured from edge of tumor to edge of tumor.
  6. For the first 18 patients: Be willing to undergo repeat biopsy of a tumor lesion before treatment and after radiation. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may be exempted from this requirement after consultation with the Principal Investigator.
  7. Have a performance status of 0 or 1 on the ECOG Performance Scale.
  8. Demonstrate adequate organ function
  9. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  10. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  11. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria:

  1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a dose of >10 mg Prednisone daily or equivalent at time of first dose of trial treatment.
  3. Has a known history of active TB (Bacillus Tuberculosis)
  4. Hypersensitivity to pembrolizumab or any of its excipients.
  5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

    Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.

    Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

  7. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  8. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  9. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  10. Has known history of, or any evidence of active, non-infectious pneumonitis.
  11. Has an active infection requiring systemic therapy.
  12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  14. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
  15. If known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA qualitative is detected) then patient is not eligible for cohorts including SBRT to liver lesions.
  16. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed, however intranasal influenza vaccines are live attenuated vaccines and are not allowed.
  17. Has had prior radiation therapy (defined as >1Gy) to the area planning to be treated with SBRT
Open or close this module Contacts/Locations
Central Contact Person: Jason J. Luke, M.D.
Telephone: 773 834 3096
Study Officials: Jason J. Luke, M.D.
Principal Investigator
University of Chicago
Locations: United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Contact:Contact: Jason J. Luke, M.D. 773-834-3096
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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