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

NCT ID: NCT02997332

Last Updated: 2019-01-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-30
• Study Completion Date: 2019-12-31

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.

Conditions

Head and Neck Cancers

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patients with squamous cell carcinoma of the oral cavity,

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.

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: DRUG

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.

Docetaxel

Intervention Type: DRUG

Docetaxel 75mg/m² on D2, IV in 1 hour

Cisplatin

Intervention Type: DRUG

Cisplatin 75mg/m² on D2, IV in 3 hours

5 Fluorouracil

Intervention Type: DRUG

5 Fluorouracil 750mg/m²/day on D2, D3, D4, D5, D6 IV in 24 hours

Interventions

Durvalumab

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

Docetaxel

Docetaxel 75mg/m² on D2, IV in 1 hour

Intervention Type: DRUG

Cisplatin

Cisplatin 75mg/m² on D2, IV in 3 hours

Intervention Type: DRUG

5 Fluorouracil

5 Fluorouracil 750mg/m²/day on D2, D3, D4, D5, D6 IV in 24 hours

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute, France

OTHER_GOV

Sponsor Role: collaborator

Gustave Roussy, Cancer Campus, Grand Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Gustave Roussy

Villejuif, Val De Marne, France

Site Status: RECRUITING

Countries

France

Central Contacts

Caroline EVEN, MD

Role: CONTACT

caroline.even@gustaveroussy.fr

0142116537 ext. +33

Matthieu TEXIER

Role: CONTACT

matthieu.texier@gustaveroussy.fr

0142116309 ext. +33

Facility Contacts

Caroline EVEN, MD

Role: primary

caroline.even@gustaveroussy.fr

0142116537 ext. +33

Matthieu TEXIER

Role: backup

matthieu.texier@gustaveroussy.fr

0142116309 ext. +33

Other Identifiers

2015/2316

Identifier Type: OTHER

Identifier Source: secondary_id

2015-004146-25

Identifier Type: -

Identifier Source: org_study_id