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

NCT02997332 | Terminated Phase 1 DMC

• 2 other identifiers: 2015-004146-252015/2316
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• 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

  Up to 10 weeks

• 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

  Up to 6 weeks

Study Arms (1)

Patients with squamous cell carcinoma of the oral cavity,

EXPERIMENTAL

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.

Drug: Durvalumab; Drug: Docetaxel; Drug: Cisplatin; Drug: 5 Fluorouracil

Interventions

5 Fluorouracil DRUG

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

Patients with squamous cell carcinoma of the oral cavity,

Durvalumab 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.

Patients with squamous cell carcinoma of the oral cavity,

Docetaxel DRUG

Docetaxel 75mg/m² on D2, IV in 1 hour

Patients with squamous cell carcinoma of the oral cavity,

Cisplatin DRUG

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

Patients with squamous cell carcinoma of the oral cavity,

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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,

Sponsors & Collaborators

• National Cancer Institute, France: collaborator
• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (1)

Gustave Roussy

Villejuif, Val de Marne, 94805, France

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

durvalumab; Docetaxel; Cisplatin; Fluorouracil

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2016
• First Posted: December 20, 2016
• Study Start: March 30, 2017
• Primary Completion: March 17, 2020
• Study Completion: December 1, 2022
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)