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Durvalumab in Combination With Docetaxel, Cisplatin and 5-FU for Locally Advanced Head and Neck Squamous Cell Carcinoma (MEDINDUCTION)

Primary Purpose

Head and Neck Cancers

Status
Unknown status
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Durvalumab
Docetaxel
Cisplatin
5 Fluorouracil
Sponsored by
Gustave Roussy, Cancer Campus, Grand Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancers

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥ 18 years and < 75 years
  2. Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx, previously untreated, amenable to induction chemotherapy according to the investigator. Patients with a diagnosis of SCCHN of occult primary could be enrolled.
  3. Absence of metastases determined by CT scan or PET scan
  4. ECOG performance status < 1
  5. Subjects must have at least 1 measurable lesion per RECIST v1.1 guidelines
  6. Adequate organ and marrow function as defined below:

    • Hemoglobin ≥ 9,0 g/dL
    • Absolute neutrophil count (ANC) ≥ 1,500/mm3
    • Platelet count ≥ 100,000/mm3
    • AST and ALT ≤ 2.5 × institutional upper limit of normal (ULN);
    • Total bilirubin ≤ 1.5 × ULN;
    • Creatinine clearance > 60 mL/min as determined by the Cockcroft-Gault equation (Cockcroft and Gault, 1976) or by 24-hour urine collection for determination of creatinine clearance
  7. Negative serology for hepatitis B and C
  8. Availability of a recent formalin-fixed tumour tissue (< 3 months) to determine HPV status and for translational research (IHC)

    a. All patients without available tumour tissue will undergo a panendoscopy with biopsies.

  9. Women of childbearing potential must have a negative serum β-HCG pregnancy test within 7 days prior to the administration of the first study treatment and/or urine pregnancy 48 hours prior to the administration of the first study treatment. Both sexually active women of childbearing potential and males (and their female partners) patients must agree to use two methods of effective contraception, one of them being a barrier method, or to abstain from sexual activity during the study and for at least 6 months after last dose of study drugs.
  10. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
  11. Patients must be affiliated to a Social Security System or beneficiary of the same
  12. Patient information and written informed consent form signed

Exclusion Criteria:

  1. Primary site of head and neck carcinoma in nasopharynx, or skin
  2. Patients receiving other anti-cancer medication such as, chemotherapy, immunotherapy, biologic therapy, targeted therapy, monoclonal antibodies, hormonal therapy (other than leuprolide or other GnRH agonists) or other investigational agent within 30 days prior to the first dose of study drug and while on study treatment.
  3. Patients receiving other anti-cancer non-drug therapies: radiation, or tumor embolization within 30 days prior to the first dose of study drug and while on study treatment.
  4. No relevant toxicities (>grade 1 CTCAE) due to prior medical treatment at time of study entry
  5. Participation in another clinical study with an investigational product during the last 30 days
  6. Patient with dihydropyrimidine dehydrogenase (DPD) deficiency
  7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active peptic ulcer disease or gastritis, active bleeding diatheses. Or patient under guardianship or deprived of his liberty by a judicial or administrative decision or any condition (e.g psychiatric illness/social/familial/geographical condition) that would limit compliance with study requirement or compromise the ability of the subject to give written informed consent
  8. Patient with active cardiac disease or with a history of cardiac dysfunction any of the following:

    • Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO),
    • Mean QT interval corrected for heart rate (QTc) ≥ 470 msec calculated from 3 electrocardiograms (ECGs) performed at screening, using Fredericia's correction (QTcF),
    • Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function,
    • Unstable angina pectoris
    • Uncontrolled hypertension
    • History of documented congestive heart failure (New York Heart Association functional classification III-IV), or Uncontrolled symptomatic congestive heart failure
    • Documented cardiomyopathy,
    • Other cardiac arrhythmia not controlled with medication.
  9. Other invasive malignancy within 5 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured
  10. Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, 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
  11. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab
  12. Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
  13. Active or prior documented inflammatory bowel disease (eg, Crohn's disease,ulcerative colitis)
  14. History of primary immunodeficiency
  15. History of allogenic organ transplant that requires use of immunosuppressives
  16. Known history of previous clinical diagnosis of tuberculosis
  17. Patients with a known HIV status
  18. Pregnant or breast-feeding women
  19. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
  20. History of hypersensitivity to durvalumab or any excipients or to other humanized mAbs
  21. Any contraindication to the use of cisplatin, docetaxel and 5FU and/or known history of hypersensitivity to any of those drugs
  22. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results

Sites / Locations

  • Gustave RoussyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patients with squamous cell carcinoma of the oral cavity,

Arm Description

The aim is to evaluate safety, PK and pharmacodynamics of durvalumab in adult patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx previously untreated, with indication of induction chemotherapy.

Outcomes

Primary Outcome Measures

Recommended Phase 2 dose (RP2D)
To determine the recommended Phase 2 dose (RP2D) and schedule of durvalumab when administered with docetaxel, cisplatin and 5 Fluorouracil
Number of Dose Limiting Toxicity (DLT)
To characterize the safety and tolerability profile of durvalumab when administered in combination with docetaxel, cisplatin and 5 Fluorouracil

Secondary Outcome Measures

Full Information

First Posted
December 13, 2016
Last Updated
January 2, 2019
Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Collaborators
National Cancer Institute, France
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1. Study Identification

Unique Protocol Identification Number
NCT02997332
Brief Title
Durvalumab in Combination With Docetaxel, Cisplatin and 5-FU for Locally Advanced Head and Neck Squamous Cell Carcinoma
Acronym
MEDINDUCTION
Official Title
Phase I Trial Evaluating the Safety of Durvalumab in Combination With Docetaxel, Cisplatin and 5-FU in Induction for Locally Advanced Head and Neck Squamous Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
March 30, 2017 (Actual)
Primary Completion Date
December 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Collaborators
National Cancer Institute, France

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 prognosis of patients with locally advanced SCCHN is poor. Results of recent randomized trials evaluating induction chemotherapy by docetaxel, cisplatin, 5 fluorouracil are conflicting, and benefit on overall survival is uncertain. Improve efficacy of induction chemotherapy is important without increase toxicities. Durvalumab is a promising agent in SSCHN. The safety of combination of docetaxel, cisplatin, 5 fluorouracil with durvalumab is unknown. The aim of the study is to evaluate the feasibility and the safety of the association of DCF (standard regimen for induction in SSCCHN) and durvalumab. The safety profile of DCF and durvalumab are different, so the expected toxicities should not be additive. The addition of durvalumab to DCF could improve the efficacy of induction chemotherapy and the prognostic of patients with SSCCHN. Concerning the translational research, the aim will be to explore the relationships between immune capacity, specificity, activation state and clinical outcome to help elucidate the determinants of response to immunotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancers

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Patients with squamous cell carcinoma of the oral cavity,
Arm Type
Experimental
Arm Description
The aim is to evaluate safety, PK and pharmacodynamics of durvalumab in adult patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx previously untreated, with indication of induction chemotherapy.
Intervention Type
Drug
Intervention Name(s)
Durvalumab
Intervention Description
Durvalumab will be administered every 3 weeks for 3 injections at week 1, 4, 7. Dose levels: the durvalumab first dose level is 1120 mg Q3W, and the dose level -1 is 750 mg Q3W.
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
Docetaxel 75mg/m² on D2, IV in 1 hour
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Cisplatin 75mg/m² on D2, IV in 3 hours
Intervention Type
Drug
Intervention Name(s)
5 Fluorouracil
Intervention Description
5 Fluorouracil 750mg/m²/day on D2, D3, D4, D5, D6 IV in 24 hours
Primary Outcome Measure Information:
Title
Recommended Phase 2 dose (RP2D)
Description
To determine the recommended Phase 2 dose (RP2D) and schedule of durvalumab when administered with docetaxel, cisplatin and 5 Fluorouracil
Time Frame
Up to 10 weeks
Title
Number of Dose Limiting Toxicity (DLT)
Description
To characterize the safety and tolerability profile of durvalumab when administered in combination with docetaxel, cisplatin and 5 Fluorouracil
Time Frame
Up to 6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years and < 75 years Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx, previously untreated, amenable to induction chemotherapy according to the investigator. Patients with a diagnosis of SCCHN of occult primary could be enrolled. Absence of metastases determined by CT scan or PET scan ECOG performance status < 1 Subjects must have at least 1 measurable lesion per RECIST v1.1 guidelines Adequate organ and marrow function as defined below: Hemoglobin ≥ 9,0 g/dL Absolute neutrophil count (ANC) ≥ 1,500/mm3 Platelet count ≥ 100,000/mm3 AST and ALT ≤ 2.5 × institutional upper limit of normal (ULN); Total bilirubin ≤ 1.5 × ULN; Creatinine clearance > 60 mL/min as determined by the Cockcroft-Gault equation (Cockcroft and Gault, 1976) or by 24-hour urine collection for determination of creatinine clearance Negative serology for hepatitis B and C Availability of a recent formalin-fixed tumour tissue (< 3 months) to determine HPV status and for translational research (IHC) a. All patients without available tumour tissue will undergo a panendoscopy with biopsies. Women of childbearing potential must have a negative serum β-HCG pregnancy test within 7 days prior to the administration of the first study treatment and/or urine pregnancy 48 hours prior to the administration of the first study treatment. Both sexually active women of childbearing potential and males (and their female partners) patients must agree to use two methods of effective contraception, one of them being a barrier method, or to abstain from sexual activity during the study and for at least 6 months after last dose of study drugs. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures Patients must be affiliated to a Social Security System or beneficiary of the same Patient information and written informed consent form signed Exclusion Criteria: Primary site of head and neck carcinoma in nasopharynx, or skin Patients receiving other anti-cancer medication such as, chemotherapy, immunotherapy, biologic therapy, targeted therapy, monoclonal antibodies, hormonal therapy (other than leuprolide or other GnRH agonists) or other investigational agent within 30 days prior to the first dose of study drug and while on study treatment. Patients receiving other anti-cancer non-drug therapies: radiation, or tumor embolization within 30 days prior to the first dose of study drug and while on study treatment. No relevant toxicities (>grade 1 CTCAE) due to prior medical treatment at time of study entry Participation in another clinical study with an investigational product during the last 30 days Patient with dihydropyrimidine dehydrogenase (DPD) deficiency Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active peptic ulcer disease or gastritis, active bleeding diatheses. Or patient under guardianship or deprived of his liberty by a judicial or administrative decision or any condition (e.g psychiatric illness/social/familial/geographical condition) that would limit compliance with study requirement or compromise the ability of the subject to give written informed consent Patient with active cardiac disease or with a history of cardiac dysfunction any of the following: Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO), Mean QT interval corrected for heart rate (QTc) ≥ 470 msec calculated from 3 electrocardiograms (ECGs) performed at screening, using Fredericia's correction (QTcF), Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function, Unstable angina pectoris Uncontrolled hypertension History of documented congestive heart failure (New York Heart Association functional classification III-IV), or Uncontrolled symptomatic congestive heart failure Documented cardiomyopathy, Other cardiac arrhythmia not controlled with medication. Other invasive malignancy within 5 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, 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 Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded Active or prior documented inflammatory bowel disease (eg, Crohn's disease,ulcerative colitis) History of primary immunodeficiency History of allogenic organ transplant that requires use of immunosuppressives Known history of previous clinical diagnosis of tuberculosis Patients with a known HIV status Pregnant or breast-feeding women Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab History of hypersensitivity to durvalumab or any excipients or to other humanized mAbs Any contraindication to the use of cisplatin, docetaxel and 5FU and/or known history of hypersensitivity to any of those drugs Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Caroline EVEN, MD
Phone
0142116537
Ext
+33
Email
caroline.even@gustaveroussy.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Matthieu TEXIER
Phone
0142116309
Ext
+33
Email
matthieu.texier@gustaveroussy.fr
Facility Information:
Facility Name
Gustave Roussy
City
Villejuif
State/Province
Val De Marne
ZIP/Postal Code
94805
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caroline EVEN, MD
Phone
0142116537
Ext
+33
Email
caroline.even@gustaveroussy.fr
First Name & Middle Initial & Last Name & Degree
Matthieu TEXIER
Phone
0142116309
Ext
+33
Email
matthieu.texier@gustaveroussy.fr

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Durvalumab in Combination With Docetaxel, Cisplatin and 5-FU for Locally Advanced Head and Neck Squamous Cell Carcinoma

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