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FRAIL-IMMUNE (GORTEC 2018-03) - Combination of Durvalumab With Carboplatin/Paclitaxel (FRAIL-IMMUNE)

Primary Purpose

Squamous Cell Carcinoma of the Head and Neck

Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Durvalumab with Carboplatin/Paclitaxel
Sponsored by
Centre Leon Berard
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Squamous Cell Carcinoma of the Head and Neck focused on measuring Squamous Cell Carcinoma of the Head and Neck, Recurrent / metastatic SCCHN, Frail patients, GORTEC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥ 18 years at the time of study entry;
  2. Histological or cytological confirmation of the diagnosis of Squamous Cell Carcinoma of the Head and Neck;
  3. Primary tumor located in one of the following : oral cavity, larynx, oropharynx or hypopharynx (NB: sinuses and nasopharynx locations are not allowed; isolated cervical lymphnodes with unknown primary site may be discussed with the coordinating investigator on a case by case basis)
  4. Archival tumor sample available at the time of inclusion with sufficient material to achieve the translational research program. Archival material must have been collected 3 months before inclusion at the latest, unless a new tumor sample must be collected.
  5. Disease must be in metastatic (Stage IVc) or recurrent setting;
  6. Documented progression of measurable disease as per the RECIST 1.1 (NB: in case of a single metastatic lesion, the tumor size must be > 20mm to allow tumor biopsy)
  7. Patients must be ineligible to standard therapies, including cisplatin. Ineligibility is defined as at least one of the following criteria:

    • Creatinine clearance (CrCl) : 40 < CrCl < 60ml/min
    • Any severe comorbidity rendering the patient ineligible to standard chemotherapy, as per investigator's judgment.
  8. Eastern Cooperative Oncology Group performance status of 0, 1 or 2
  9. Must have a life expectancy of at least 12 weeks
  10. Body weight > 30Kg;
  11. Adequate organ and marrow function as defined below:

    • Hemoglobin ≥ 9.0 g/dl
    • Absolute Neutrophils Count (ANC) ≥ 1.5 x 109/L
    • Platelet count ≥ 100 x 109/L
    • Creatinine clearance ≥ 40 ml/min using the following appropriate formulae:

      • Cockroft-Gault formula for female : 0.85 x weight (Kg) x (140-age) / 72 x serum creatinine (mg/dL)
      • Cockroft-Gault formula for male : weight (Kg) x (140-age) / 72 x serum creatinine (mg/dL)
      • MDRD for patients older than 65 years: 186.3 x (serum creatinine (µmol/L / 88.4) -1.154 x Age -0.203 x (0.742 if female) x (1.212 if black patient [African origin]).
    • AST/ALT ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5 x ULN
    • Serum total bilirubin ≤ 1.5 x ULN (in the absence of Gilbert's syndrome)
    • Coagulation panel : INR or PT ≤ 1.5 x ULN
  12. 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 age-specific requirements apply:

    • 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).
    • 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).
  13. Patient (male or female) using a highly effective contraception as defined in appendix 9 during the study treatment period and until 6 months after the last administration of carboplatin and/or paclitaxel or until 90 days after the last administration of durvalumab, whichever is longer. Prior to dispensing study drugs, the investigator must confirm and document the patient's (and his/her partner) use of highly effective contraceptive methods, dates of negative pregnancy tests, and confirm the patient's understanding of the teratogenic potential of study drugs.
  14. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  15. Covered by a medical insurance.
  16. Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrolment

Exclusion Criteria:

  1. History of another primary malignancy except for:

    • Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
    • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    • Adequately treated carcinoma in situ without evidence of disease
  2. Prior anticancer therapy in metastatic or recurrent setting In case patient received neoadjuvant or adjuvant anti-cancer treatment, it must have been completed for at least 6 months prior to study drugs initiation and patient must have no unresolved toxicity NCI CTCAE Grade ≥2 with the exception of alopecia, vitiligo and laboratory values defined as inclusion criteria.

    Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the coordinating investigator.

    Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the coordinating investigator.

  3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
  4. Patient whom tumor lesion is hemorrhagic or at risk of bleeding
  5. Patient whom disease progressed within 6 months after the start date of the previous chemotherapy (faster progressors)
  6. Symptomatic or active leptomeningial or parenchymal brain metastases. Patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment ot the brain metastases; these Imaging scans should both be obtained at least 4 weeks apart and show no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of <=10mg/day of prednisone or its equivalent and anticonvulsant for at least 14 days prior to the start of treatment.
  7. Active or prior/history of disease/medical condition listed below:

    • Inflammatory or interstitial lung disease
    • Documented autoimmune or inflammatory disease (including inflammatory bowel disease [e.g., Crohn's disease, ulcerative colitis], systemic lupus erythematosus, sarcoidosis syndrome or Wegener syndrome, granulomatosis with polyangitis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis, etc) within the past 2 years except for autoimmune hypothyroidism on a stable dose of thyroid supplementation and patients with type 1 diabetes mellitus on a stable dose of insulin.

    Note: Subjects with alopecia, vitiligo, psoriasis not requiring systemic treatment (within the past 2 years) or chronic skin condition that does not require systemic therapy, are not excluded, as well as patients without active disease in the last 5 years (after consultation with the study physician) and patients with celiac disease controlled by diet alone.

    • Mean QT interval corrected for heart rate (QTc) ≥470 ms using Fredericia's Correction.
    • Clinically significant cardiac disease or congestive heart failure > New York Heart Association (NYHA) class 2. Patients must not have unstable angina (anginal symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months.
    • History of primary immunodeficiency
    • Allogeneic organ transplantation
    • Documented hypersensitivity to the active substance or excipient of the study drugs
    • Any uncontrolled intercurrent illness including, but not limited to:

      • Ongoing or active infection, including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), 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.
      • Active peptic ulcer disease or gastritis,
      • Active bleeding diatheses including any subject known to have evidence of acute risk,
      • Serious chronic gastrointestinal conditions associated with diarrhea
    • Any psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
  8. Current or prior use, or need for the following concomitant medications/interventions not permitted during the study treatment period :

    • Any concurrent chemotherapy or radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug (except palliative radiotherapy on a non-target lesion after discussion with the coordinating investigator), immunotherapy, biologic or hormonal therapy for cancer treatment, other than any stated in the protocol (Note: concurrent use of hormonal therapy for non-cancer-related conditions (e.g. hormone replacement therapy) is acceptable)).
    • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab including, but not limited to systemic corticosteroids at doses exceeding 10 mg/day of prednisone or equivalent, methotrexate, azathioprine, and TNF-α blockers. Use of immunosuppressive medications for the management of investigational product-related AEs or in subjects with contrast allergies is acceptable.
    • Phenytoin given in a prophylactic intent
    • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP (Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP).

      • Strong inhibitors and inducers of CYP3A4
      • 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.
  9. Participation in another clinical study with an investigational product during the last 28 days prior to first study drug administration
  10. Pregnant or breastfeeding women (Women of childbearing potential are required to have a negative serum pregnancy test within 72 hours prior to study treatment start. A positive urine test must be confirmed by a serum pregnancy test).

Sites / Locations

  • CHU d'Amiens
  • ICO - Centre Paul Papin
  • Institut Sainte-CatherineRecruiting
  • Centre Georges-François LeclercRecruiting
  • Clinique des OrmeauxRecruiting
  • Groupe hospitalier Bretagne SudRecruiting
  • Hôpital de la Croix-RousseRecruiting
  • Centre Léon BérardRecruiting
  • Hôpital de la TimoneRecruiting
  • ICM - Centre Val d'AurelleRecruiting
  • Hôpital Privé du ConfluentRecruiting
  • Centre Henri BecquerelRecruiting
  • ICO - Centre René GauducheauRecruiting
  • Clinique Mutualiste de l'Estuaire
  • Centre Paul StraussRecruiting
  • Institut de Cancérologie de Lorraine Alexis VautrinRecruiting
  • Institut Gustave RoussyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Durvalumab with Carboplatin/Paclitaxel

Arm Description

Combination of Durvalumab with Carboplatin/Paclitaxel as first line treatment in patients with recurrent/metastatic SCCHN not eligible to standard chemotherapy

Outcomes

Primary Outcome Measures

Evaluation of efficacy and safety of Durvalumab with the Carboplatin/Paclitaxel as first line treatment in patients with recurrent/metastatic SCCHN not eligible to standard chemotherapy
Number of patients still alive 12 months after the first study drug administration (overall survival)

Secondary Outcome Measures

Progression-Free Survival
Defined as the time from the date of the first study drug administration to the date of first documented progression or death due to any cause
Time to Treatment Failure
Defined as the time from the date of inclusion to the date of permanent study treatment discontinuation
Overall survival
Defined as the time from the date of inclusion to the date of death due to any cause
Objective Response Rate
Defined as the proportion of patients with a best overall response of Complete or Partial Response
Best Response Rate
Defined as proportion of patients who achieve a best response of CR, PR, SD or PD
Duration of response
Defined as the time from the date of first documented response (CR or PR) to the date of the first documented subsequent progression or death due to any cause
Quality of life using European Organisation for Research and Treatment of Cancer (EORTC) questionnaire
Using the EORTC QLQ-C30 (Quality of Life Questionnaire) - Scale range: 1 (better outcome) to 4 (worse outcome) for 28 variables and from 1 (better outcome) to 7 (worse outcome) for 2 variables
Quality of life using European Organisation for Research and Treatment of Cancer (EORTC) questionnaire
Using the EORTC QLQ-H&N35 questionnaire (Quality of Life Questionnaire) - Scale range: 1 (better outcome) to 4 (worse outcome) for 30 variables and from 1 (better outcome) to 2 (worse outcome) for 5 variables
Tolerance profile: Incidence of treatment emergent adverse events and serious adverse events
Incidence of Treatment Emergent Adverse Events, Serious Adverse Events (SAE) and death assessed according to the NCI-CTC AE version 5

Full Information

First Posted
October 18, 2018
Last Updated
October 3, 2022
Sponsor
Centre Leon Berard
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1. Study Identification

Unique Protocol Identification Number
NCT03723967
Brief Title
FRAIL-IMMUNE (GORTEC 2018-03) - Combination of Durvalumab With Carboplatin/Paclitaxel
Acronym
FRAIL-IMMUNE
Official Title
Multicenter Prospective Single Arm Phase II Study Evaluating Efficacy & Safety of Durvalumab With Carboplatin/Paclitaxel as First Line Treatment in Patients With Recurrent/Metastatic SCCHN Not Eligible to Standard Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 16, 2019 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Leon Berard

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective of the phase II trial is to determine the efficacy and safety of a combination of Durvalumab with the Carboplatin/Paclitaxel as first line treatment in patients with recurrent/metastatic SCCHN not eligible to standard chemotherapy.
Detailed Description
For recurrent or metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN), the standard first-line treatment is chemotherapy by cisplatin-fluorouracil and cetuximab which allows a median overall survival of 10.1 months. Due to its toxicity, this combination could be proposed only to patients younger than 70 years, good PS (ECOG PS0 or PS1) and adequate renal function. In routine practice it is estimated that the proportion of eligible patients is about two third. One third of patients were ineligible to first-line chemotherapy by cisplatin-fluorouracil-cetuximab. Among them, 25% due to PS2 and the others for various reasons (older than 70 years, renal insufficiency….). For these ineligible patients, an alternative chemotherapy should be proposed. The carboplatin-paclitaxel scheme with weekly paclitaxel is safe for poor population and demonstrated efficacy in head and neck cancers with overall survival varying from 4.9 months to 12.8 months in first line. The response rate varies from 20% to 52% and is about 25% in our experience. Even for frail patients it should be a safe and active treatment. Nivolumab, a monoclonal antibody targeting PD1 demonstrated survival benefit compared with chemotherapy in patients with SCCHN who progressed after platinum-based first line (median OS of 7.5 months versus 5.1 months and 12-month OS rate of 36.0% versus 16.6%). Safety data confirm these antibodies are of interest in a population of frail patients. Only 58.9% of patients experienced treatment-related adverse events with nivolumab arm and 13% of grade 3/4. Durvalumab, an anti-PDL1 antibody is currently tested in SCCHN with promising results. Head and neck cancers are rapidly progressive and due to the delayed action of immunotherapy, and the recent demonstration that immunotherapy with anti-PD1 or anti-PDL1 can be responsible of hyperprogression, patients will probably benefit from addition of chemotherapy to immunotherapy, mostly for patients unfit for cisplatin-fluorouracil because their poor condition is often related to the cancer and a rapid response is needed. This trial proposes to study the addition of Durvalumab to chemotherapy in first line treatment for frail patients with recurrent/metastatic SCCHN. Prior to this evaluation, a run-in tolerance study in a limited number of patients to ensure that the experimental treatment combination is safe.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma of the Head and Neck
Keywords
Squamous Cell Carcinoma of the Head and Neck, Recurrent / metastatic SCCHN, Frail patients, GORTEC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Multicenter, prospective, single arm phase II study (a run-in tolerance study will be first performed on a limited number of patients: maximum 9)
Masking
None (Open Label)
Allocation
N/A
Enrollment
102 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Durvalumab with Carboplatin/Paclitaxel
Arm Type
Experimental
Arm Description
Combination of Durvalumab with Carboplatin/Paclitaxel as first line treatment in patients with recurrent/metastatic SCCHN not eligible to standard chemotherapy
Intervention Type
Drug
Intervention Name(s)
Durvalumab with Carboplatin/Paclitaxel
Other Intervention Name(s)
Combination of Durvalumab with Carboplatin/Paclitaxel
Intervention Description
Durvalumab associated with Carboplatin / Paclitaxel as first line treatment in patients with recurrent/metastatic SCCHN not eligible to standard chemotherapy
Primary Outcome Measure Information:
Title
Evaluation of efficacy and safety of Durvalumab with the Carboplatin/Paclitaxel as first line treatment in patients with recurrent/metastatic SCCHN not eligible to standard chemotherapy
Description
Number of patients still alive 12 months after the first study drug administration (overall survival)
Time Frame
12 months after study treatment initiation
Secondary Outcome Measure Information:
Title
Progression-Free Survival
Description
Defined as the time from the date of the first study drug administration to the date of first documented progression or death due to any cause
Time Frame
12 months after study treatment initiation
Title
Time to Treatment Failure
Description
Defined as the time from the date of inclusion to the date of permanent study treatment discontinuation
Time Frame
12 months after study treatment initiation
Title
Overall survival
Description
Defined as the time from the date of inclusion to the date of death due to any cause
Time Frame
Up to 36 months
Title
Objective Response Rate
Description
Defined as the proportion of patients with a best overall response of Complete or Partial Response
Time Frame
12 months after study treatment initiation
Title
Best Response Rate
Description
Defined as proportion of patients who achieve a best response of CR, PR, SD or PD
Time Frame
12 months after study treatment initiation
Title
Duration of response
Description
Defined as the time from the date of first documented response (CR or PR) to the date of the first documented subsequent progression or death due to any cause
Time Frame
12 months after study treatment initiation
Title
Quality of life using European Organisation for Research and Treatment of Cancer (EORTC) questionnaire
Description
Using the EORTC QLQ-C30 (Quality of Life Questionnaire) - Scale range: 1 (better outcome) to 4 (worse outcome) for 28 variables and from 1 (better outcome) to 7 (worse outcome) for 2 variables
Time Frame
12 months after study treatment initiation
Title
Quality of life using European Organisation for Research and Treatment of Cancer (EORTC) questionnaire
Description
Using the EORTC QLQ-H&N35 questionnaire (Quality of Life Questionnaire) - Scale range: 1 (better outcome) to 4 (worse outcome) for 30 variables and from 1 (better outcome) to 2 (worse outcome) for 5 variables
Time Frame
12 months after study treatment initiation
Title
Tolerance profile: Incidence of treatment emergent adverse events and serious adverse events
Description
Incidence of Treatment Emergent Adverse Events, Serious Adverse Events (SAE) and death assessed according to the NCI-CTC AE version 5
Time Frame
12 months after study treatment initiation
Other Pre-specified Outcome Measures:
Title
Determination as predictive & prognostic factors of efficacy: Time to recurrence
Description
Time to recurrence in patients with localized disease at diagnosis.
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Determination as predictive & prognostic factors of efficacy : Site of recurrence
Description
Site of recurrence (in or outside a previous irradiation field for patients who have previously received radiation therapy)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Determination as predictive & prognostic factors of efficacy: Level of expression of PD-L1
Description
Determined by immunohistochemistry (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (eachy cycle is 28 days), First documented radiological progression
Title
Determination as predictive & prognostic factors of efficacy: Level of expression of p16
Description
Determined by immunohistochemistry (archival formalin fixed paraffin embedded tumor sample)embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Determination as predictive & prognostic factors of efficacy: Level of HPV for patients presenting an oropharynx tumour and a tumor with a positive p16
Description
Determined by immunohistochemistry (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: Immune infiltrate assessment: CD3 analysis
Description
Determined by multiIF (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: Immune infiltrate assessment: CD8 (T cells) analysis
Description
Determined by multiIF (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: Immune infiltrate assessment: CD20 analysis
Description
Determined by multiIF (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: Immune infiltrate assessment: CD38 analysis
Description
Determined by multiIF (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: Immune infiltrate assessment: IgG analysis
Description
Determined by multiIF (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: Immune infiltrate assessment: NKp46 analysis
Description
Determined by multiIF (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: Immune infiltrate assessment: FOXP3
Description
Determined by multiIF (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: Immune infiltrate assessment: CD4 analysis
Description
Determined by multiIF (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: Immune infiltrate assessment: CD8 analysis
Description
Determined by multiIF (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: Immune infiltrate assessment: Treg analysis
Description
Determined by multiIF (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: Immune infiltrate assessment: NK analysis
Description
Determined by multiIF (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: Immune infiltrate assessment: Monocytes analysis
Description
Determined by multiIF (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: Immune infiltrate assessment: DC analysis
Description
Determined by multiIF (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: Mutation of genes
Description
Using PROFILER panel (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: Transcriptome
Description
Using RNAseq if possible or HTG (archival formalin fixed paraffin embedded tumor sample)
Time Frame
Inclusion, Day 1 cycle 2 (each cycle is 28 days), First documented radiological progression
Title
Optional outcome: PBMC (in selected sites only)
Description
Evaluation of PBMC (blood samples)
Time Frame
Inclusion, Day 1 of cycles 2, 3, 4 and 5 (each cycle is 28 days), End of treatment plus 30 days
Title
Optional outcome: ctDNA for a panel of selected genes
Description
Evaluation of ctDNA (panel of genes to be selected at the time of analysis) (blood samples)
Time Frame
Inclusion, Day 1 of cycles 2, 3, 4 and 5 (each cycle is 28 days), End of treatment plus 30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years at the time of study entry; Histological or cytological confirmation of the diagnosis of Squamous Cell Carcinoma of the Head and Neck; Primary tumor located in one of the following : oral cavity, larynx, oropharynx or hypopharynx (NB: sinuses and nasopharynx locations are not allowed; isolated cervical lymphnodes with unknown primary site may be discussed with the coordinating investigator on a case by case basis) Archival tumor sample available at the time of inclusion with sufficient material to achieve the translational research program. Archival material must have been collected 3 months before inclusion at the latest, unless a new tumor sample must be collected. Disease must be in metastatic (Stage IVc) or recurrent setting; Documented progression of measurable disease as per the RECIST 1.1 (NB: in case of a single metastatic lesion, the tumor size must be > 20mm to allow tumor biopsy) Patients must be ineligible to standard therapies, including cisplatin. Ineligibility is defined as at least one of the following criteria: Creatinine clearance (CrCl) : 40 < CrCl < 60ml/min Any severe comorbidity rendering the patient ineligible to standard chemotherapy, as per investigator's judgment. Eastern Cooperative Oncology Group performance status of 0, 1 or 2 Must have a life expectancy of at least 12 weeks Body weight > 30Kg; Adequate organ and marrow function as defined below: Hemoglobin ≥ 9.0 g/dl Absolute Neutrophils Count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Creatinine clearance ≥ 40 ml/min using the following appropriate formulae: Cockroft-Gault formula for female : 0.85 x weight (Kg) x (140-age) / 72 x serum creatinine (mg/dL) Cockroft-Gault formula for male : weight (Kg) x (140-age) / 72 x serum creatinine (mg/dL) MDRD for patients older than 65 years: 186.3 x (serum creatinine (µmol/L / 88.4) -1.154 x Age -0.203 x (0.742 if female) x (1.212 if black patient [African origin]). AST/ALT ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5 x ULN Serum total bilirubin ≤ 1.5 x ULN (in the absence of Gilbert's syndrome) Coagulation panel : INR or PT ≤ 1.5 x ULN 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 age-specific requirements apply: 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). 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). Patient (male or female) using a highly effective contraception as defined in appendix 9 during the study treatment period and until 6 months after the last administration of carboplatin and/or paclitaxel or until 90 days after the last administration of durvalumab, whichever is longer. Prior to dispensing study drugs, the investigator must confirm and document the patient's (and his/her partner) use of highly effective contraceptive methods, dates of negative pregnancy tests, and confirm the patient's understanding of the teratogenic potential of study drugs. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. Covered by a medical insurance. Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrolment Exclusion Criteria: History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease Prior anticancer therapy in metastatic or recurrent setting In case patient received neoadjuvant or adjuvant anti-cancer treatment, it must have been completed for at least 6 months prior to study drugs initiation and patient must have no unresolved toxicity NCI CTCAE Grade ≥2 with the exception of alopecia, vitiligo and laboratory values defined as inclusion criteria. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the coordinating investigator. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the coordinating investigator. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab. Patient whom tumor lesion is hemorrhagic or at risk of bleeding Patient whom disease progressed within 6 months after the start date of the previous chemotherapy (faster progressors) Symptomatic or active leptomeningial or parenchymal brain metastases. Patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment ot the brain metastases; these Imaging scans should both be obtained at least 4 weeks apart and show no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of <=10mg/day of prednisone or its equivalent and anticonvulsant for at least 14 days prior to the start of treatment. Active or prior/history of disease/medical condition listed below: Inflammatory or interstitial lung disease Documented autoimmune or inflammatory disease (including inflammatory bowel disease [e.g., Crohn's disease, ulcerative colitis], systemic lupus erythematosus, sarcoidosis syndrome or Wegener syndrome, granulomatosis with polyangitis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis, etc) within the past 2 years except for autoimmune hypothyroidism on a stable dose of thyroid supplementation and patients with type 1 diabetes mellitus on a stable dose of insulin. Note: Subjects with alopecia, vitiligo, psoriasis not requiring systemic treatment (within the past 2 years) or chronic skin condition that does not require systemic therapy, are not excluded, as well as patients without active disease in the last 5 years (after consultation with the study physician) and patients with celiac disease controlled by diet alone. Mean QT interval corrected for heart rate (QTc) ≥470 ms using Fredericia's Correction. Clinically significant cardiac disease or congestive heart failure > New York Heart Association (NYHA) class 2. Patients must not have unstable angina (anginal symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months. History of primary immunodeficiency Allogeneic organ transplantation Documented hypersensitivity to the active substance or excipient of the study drugs Any uncontrolled intercurrent illness including, but not limited to: Ongoing or active infection, including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), 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. Active peptic ulcer disease or gastritis, Active bleeding diatheses including any subject known to have evidence of acute risk, Serious chronic gastrointestinal conditions associated with diarrhea Any psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent Current or prior use, or need for the following concomitant medications/interventions not permitted during the study treatment period : Any concurrent chemotherapy or radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug (except palliative radiotherapy on a non-target lesion after discussion with the coordinating investigator), immunotherapy, biologic or hormonal therapy for cancer treatment, other than any stated in the protocol (Note: concurrent use of hormonal therapy for non-cancer-related conditions (e.g. hormone replacement therapy) is acceptable)). Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab including, but not limited to systemic corticosteroids at doses exceeding 10 mg/day of prednisone or equivalent, methotrexate, azathioprine, and TNF-α blockers. Use of immunosuppressive medications for the management of investigational product-related AEs or in subjects with contrast allergies is acceptable. Phenytoin given in a prophylactic intent Receipt of live attenuated vaccine within 30 days prior to the first dose of IP (Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP). Strong inhibitors and inducers of CYP3A4 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. Participation in another clinical study with an investigational product during the last 28 days prior to first study drug administration Pregnant or breastfeeding women (Women of childbearing potential are required to have a negative serum pregnancy test within 72 hours prior to study treatment start. A positive urine test must be confirmed by a serum pregnancy test).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Julien GAUTIER
Phone
+33 4.26.55.68.29
Email
julien.gautier@lyon.unicancer.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Jérôme FAYETTE, MD
Phone
+33 4.78.78.51.03
Email
jerome.fayette@lyon.unicancer.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jérôme FAYETTE, MD
Organizational Affiliation
Centre Leon Berard
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU d'Amiens
City
Amiens
ZIP/Postal Code
80054
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexandre COUTTE, MD
Facility Name
ICO - Centre Paul Papin
City
Angers
ZIP/Postal Code
59055
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Damien VANSTEENE, MD
Facility Name
Institut Sainte-Catherine
City
Avignon
ZIP/Postal Code
84918
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clémence TOULLEC, MD
Facility Name
Centre Georges-François Leclerc
City
Dijon
ZIP/Postal Code
21079
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aurélie LAGRANGE, MD
Facility Name
Clinique des Ormeaux
City
Le Havre
ZIP/Postal Code
76600
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laurent MARTIN, MD
Facility Name
Groupe hospitalier Bretagne Sud
City
Lorient
ZIP/Postal Code
56322
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian SIRE, MD
Facility Name
Hôpital de la Croix-Rousse
City
Lyon
ZIP/Postal Code
69004
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amandine BRUYAS, MD
Facility Name
Centre Léon Bérard
City
Lyon
ZIP/Postal Code
69008
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jérôme FAYETTE, MD
Phone
+33 4.78.78.51.03
Email
jerome.fayette@lyon.unicancer.fr
First Name & Middle Initial & Last Name & Degree
Jérôme FAYETTE, MD
Facility Name
Hôpital de la Timone
City
Marseille
ZIP/Postal Code
13005
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sébastien SALAS, MD
Facility Name
ICM - Centre Val d'Aurelle
City
Montpellier
ZIP/Postal Code
34298
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie VINCHES, MD
Facility Name
Hôpital Privé du Confluent
City
Nantes
ZIP/Postal Code
44277
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benjamin LINOT, MD
Facility Name
Centre Henri Becquerel
City
Rouen
ZIP/Postal Code
76038
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Florian CLATOT, MD
Facility Name
ICO - Centre René Gauducheau
City
Saint-Herblain
ZIP/Postal Code
44805
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Damien VANSTEENE, MD
Facility Name
Clinique Mutualiste de l'Estuaire
City
Saint-Nazaire
ZIP/Postal Code
44600
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thierry CHATELLIER, MD
Facility Name
Centre Paul Strauss
City
Strasbourg
ZIP/Postal Code
67065
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mickaël BURGY, MD
Facility Name
Institut de Cancérologie de Lorraine Alexis Vautrin
City
Vandœuvre-lès-Nancy
ZIP/Postal Code
54511
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie-Christine KAMINSKY, MD
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariana IACOB, MD

12. IPD Sharing Statement

Learn more about this trial

FRAIL-IMMUNE (GORTEC 2018-03) - Combination of Durvalumab With Carboplatin/Paclitaxel

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