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Trial Evaluating the Tolerance and Safety of Durvalumab - RT Combination for Treatment in SCCHN (REWRITe)

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. Identifier: NCT03726775
Recruitment Status : Recruiting
First Posted : October 31, 2018
Last Update Posted : September 9, 2019
Center Eugene Marquis
Information provided by (Responsible Party):
Groupe Oncologie Radiotherapie Tete et Cou

Brief Summary:
This study evaluate the regional (neck) nodal control of durvalumab in combination with RT restricted to the primary tumor and the immediately adjacent nodal level (i.e. without prophylactic neck irradiation) in N0 patients with SCCHN.

Condition or disease Intervention/treatment Phase
HNSCC Drug: Durvalumab Phase 2

Detailed Description:

There is a strong rationale for testing this new paradigm of RT for SCCHN without prophylactic neck irradiation, being replaced by immune stimulation via the combination of RT and Programmed Death-1 (PD-L1) inhibition with durvalumab, due to:

  • The unmet medical need for new treatments, better tolerated and " as " or " more " effective than the current Standard Of Care (SOC)
  • The need to decrease radiation-induced toxicity, especially in fragile patients
  • The added toxicity due to elective nodal irradiation
  • The strong rationale to combine RT and PD-L1 inhibition
  • The potential immune suppressive effect of large field prophylactic neck irradiation

It is hypothesized this innovative concept to be safe in the context of this study for the following reasons:

  • The rate of relapse in the neck is expected to be low in Magnetic Resonnance Imaging (MRI) & PET-CT N0 neck
  • A non-irradiated neck can be easily monitored, clinically and by imaging
  • Most of the potential relapses in the neck are expected to be salvaged by surgery and/or RT
  • The preventive irradiation of N0 regions is not anymore performed for others lymphophilic cancers (lymphoma, Non-Small Cell Lung Cancer (NSCLC)).

The combination of durvalumab with RT restricted to the primary tumor site and immediate adjacent nodal area will achieve a similarly regional (nodal) control rate than standard RT including large prophylactic neck irradiation (regional recurrence < 10 %.

This study will include patients with early (T1-T2 N0) or locally advanced SCCHN (T3-4 N0), histologically proven who had not received previous treatment for this setting. The study is designed with the primary objective of demonstrating that RT without large prophylactic irradiation in combination with durvalumab is effective in terms of regional control. All patients will be followed until death or at least 36 months.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 73 participants
Intervention Model: Single Group Assignment
Intervention Model Description: IV infusion of durvalumab will start at fixed dose on Day1 of RT and subsequently every 3 weeks during the course of RT. Durvalumab with be continued via IV infusion at a fixed dose for an additional 6 months following RT, unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Radiotherapy (RT)-Durvalumab Without Prophylactic Neck Irradiation in Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Actual Study Start Date : July 17, 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: RT-durvalumab
durvalumab at fixed dose of 1120 mg on Day1 of RT and every 3 weeks during the RT. Durvalumab with be continued at a fixed dose of 1500 mg every 4 weeks during 6 months following RT.
Drug: Durvalumab
Infusion of durvalumab during RT and after RT during 6 months
Other Name: MEDI4736

Primary Outcome Measures :
  1. Regional (neck) nodal control rate [ Time Frame: 1 year ]
    Cervical Node Control in the non-irradiated N0 neck

Secondary Outcome Measures :
  1. Recurrence and control rates analysis [ Time Frame: 3, 6, 12, 18, 24 and 36 months ]
    Estimation of local, regional, locoregional control

  2. Survival analyses [ Time Frame: 3, 7, 11, 15, 19, 23, 27, 31, and 36 months post RT ]
    Estimation of the survival rates and the 95% confidence intervals (95% CI)

  3. Objective Response Rate [ Time Frame: 3, 12, 24 et 36 months post RT ]
    complete or partial response according to RECIST 1.1 criteria

  4. Quality of life QLQC30 [ Time Frame: baseline, 3-month, 12-month and 24-month post RT ]
    To evaluate the effectiveness of support

  5. Quality of life QLQ-H&N35 [ Time Frame: baseline, 3-month, 12-month and 24-month post RT ]
    To evaluate the effectiveness of support

Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Age > 18 years with no upper limit
  2. Performance Status ECOG 0-2
  3. Non-eligible to existing SOC with chemo-RT or cetuximab-RT
  4. Squamous cell carcinoma, previously untreated
  5. T1-T2 N0 with measurable disease for whom the risk of nodal spread is estimated to be low (< 10-15%) or T3-T4 N0 with measurable disease for whom large field neck irradiation may not be appropriate due to age, and/or fragile condition (PS2)
  6. N0 neck based on clinical, MRI and FDG/PET-CT examinations
  7. Oral cavity, oropharynx, hypopharynx or larynx
  8. Availability of pre-treatment tumor tissue sample (for PD-L1 expression, TILs and immune landscape)
  9. Documentation of p16 disease (HPV status for oropharyngeal tumor)
  10. Recording of alcohol consumption and smoking history
  11. Adequate normal organ and marrow function as defined below:

1. Hemoglobin > 9.0 g/dL 2. Absolute neutrophil count (ANC) ≥ 1500 per mm3 3. Platelet count > 100 000 per mm3 4. Serum bilirubin < 1.5 x institutional upper limit of normal (ULN) 5. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional ULN 12.Measured creatinine clearance (CL) >40 mL/min (CKD-EPI method recommended) or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula 13. Patient willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations during the follow up period 14. Patient able to understand French and complete the quality of life questionnaires 15.Must have a life expectancy of at least 12 weeks 16. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following agespecific requirements apply:

  1. Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  2. Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

17. Patient capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.

Exclusion Criteria:

  1. Nasopharyngeal, paranasal sinuses, nasal cavity tumors or thyroid cancers
  2. Metastatic disease
  3. Active CNS disease
  4. Any prior or current treatment for invasive head and neck cancer
  5. Any unresolved toxicity NCI CTCAE v5.0 Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.

    1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis
    2. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the investigator
  6. Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable
  7. History of leptomeningeal carcinomatosis
  8. Body weight ≤ 30 kg and/or weight loss of ≥ 15% during the last 4 weeks (except if renutrition with a feeding tube is planned before the onset of treatment or is ongoing)
  9. Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol
  10. Concomitant treatment with any drug on the prohibited medication list such as live vaccines within 30 days prior to the first dose of IP
  11. Known allergy or hypersensitivity reaction to study drug or any of the study drug excipients
  12. Prior organ transplantation including allogenic stem-cell transplantation
  13. Other severe acute or chronic medical conditions including pneumonitis, pulmonary fibrosis
  14. Active autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc])
  15. Uncontrolled intercurrent illness, including but not limited to, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
  16. History of another primary malignancy except for:

    1. Malignancy treated with curative intent and with no known active disease ≥ 5 years
    2. Adequately treated non-melanoma skin cancer
    3. Adequately treated carcinoma in situ without evidence of disease
  17. History of active primary immunodeficiency
  18. Ongoing or active infection including tuberculosis, hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). 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
  19. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:

    1. Intranasal, inhaled, topical steroids, or local steroid injections
    2. Systemic corticosteroids < 10 mg/day of prednisone or its equivalent
    3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  20. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy
  21. Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment

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 identifier (NCT number): NCT03726775

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Contact: JEAN BOURHIS, MD (0)6 77 47 00 41 ext +33
Contact: LAURA SINIGAGLIA (0)6 08 72 48 35 ext +33

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Institut Sainte Catherine Recruiting
Avignon, France, 84082
Contact: Armelle Rollet, CRA    04 90 27 62 74   
Principal Investigator: Marc ALFONSI, MD         
Centre Eugene Marquis Recruiting
Rennes, France, 35042
Principal Investigator: Joël CSTELLI, MD         
Sponsors and Collaborators
Groupe Oncologie Radiotherapie Tete et Cou
Center Eugene Marquis

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Responsible Party: Groupe Oncologie Radiotherapie Tete et Cou Identifier: NCT03726775     History of Changes
Other Study ID Numbers: GORTEC 2018-02
First Posted: October 31, 2018    Key Record Dates
Last Update Posted: September 9, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Groupe Oncologie Radiotherapie Tete et Cou:
without prophylactic
Additional relevant MeSH terms:
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Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs