Pembrolizumab and Induction Chemotherapy in Head and Neck Squamous Cell Carcinoma (PICH Study)

NCT03114280 | Withdrawn Phase 1 DMC

• 1 other identifier: 2017/13
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Non-randomized phase I/II, open-labeled clinical study, 1-arm, multicenter, of docetaxel (T), cisplatin (P), 5-fluorouracil (F) and pembrolizumab every 21 days for 3 cycles followed by radiotherapy (RT) combined with carboplatin in untreated unresectable locally-advanced Head and Neck Squamous Cell Carcinoma (HNSCC). The TPF and pembrolizumab combination will be called TP²F.

Conditions

Head and Neck Squamous Cell Carcinoma (HNSCC)

Outcome Measures

Primary Outcomes (2)

• Phase I : Evaluation of Recommended dose for phase II and characterization of the safety and tolerability profile of pembrolizumab when administered in combination with docetaxel, cisplatin and 5 Fluorouracil

  To evaluate by using a "3+3 modified schedule" the Recommended Phase 2 Dose (RPD2), Dose Limiting Toxicities (DLT) and Maximal Tolerated Dose (MTD) of the association of pembrolizumab with induction therapy by docetaxel, cisplatin and 5-fluorouracil (TP²F) as first-line treatment for patients with locally-advanced unresectable HNSCC

  12 months post treatment

• Phase II : Progression-free survival

  Progression-free survival : To evaluate, in terms of progression-free survival rate at 12 months, the efficacy of the association of pembrolizumab with induction therapy by docetaxel, cisplatin and 5-fluorouracil (TP²F) as first-line treatment for patients with locally-advanced unresectable HNSCC ; in order to demonstrate that the addition of pembrolizumab to TPF can increase efficacy without increasing toxicity.

  12 months post treatment

Secondary Outcomes (8)

• Phase I : Antitumor activity

  24 months post treatment

• Phase II : Overall survival rate

  24 months post treatment

• Phase II : Best Overall response

  24 months post treatment

• Phase II : Best Overall response

  24 months post treatment

• Phase II : Objective response rate

  24 months post treatment

Study Arms (1)

TPF2

EXPERIMENTAL

docetaxel (T), cisplatin (P), 5 Fluorouracil (F) and pembrolizumab every 21 days followed by radiotherapy (RT) combined with carboplatin

Drug: TPF2; Other: Radiotherapy with carboplatin

Interventions

TPF2 DRUG

Combination drugs : docetaxel (T), cisplatin (P), 5 Fluorouracil (F) and pembrolizumab every 21 days

TPF2

Radiotherapy with carboplatin OTHER

Radiotherapy (RT) combined with carboplatin

TPF2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible for participation in this trial, the subject should fulfill the following criteria:
• Age \> or = 18 and \< 70 years years at the time of signing informed consent,
• Histologically or cytologically confirmed head and neck squamous-cell carcinoma (oral cavity, oropharynx and hypopharynx) with locoregionally-advanced disease stage III or IV without metastasis, previously untreated,
• Measurable disease based on RECIST 1.1,
• Performance status of 0 or 1 on the ECOG Performance Scale,
• Tumors considered unresectable by a multidisciplinary team,
• Available biopsy sample and HPV status,
• Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required,
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 180 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year,
• Male subjects should agree to use an adequate method of contraception or abstain from heterosexual activity starting with the first dose of study therapy through 180 days after the last dose of study therapy,
• Patient willing and able to provide written informed consent/assent for the trial,
• Patient affiliated with a health insurance system.

You may not qualify if:

• Tumors of the nasopharynx, larynx and the nasal and paranasal cavities,
• Hemorrhagic tumors, Protocol PICH\_version 2.0 of 02 May 2018 Page 10 sur 127
• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of treatment,
• Before the first dose of trial treatment:
• a) Had major surgery (\< 4 weeks prior to the first dose), Note: If subject received major surgery, he must have recovered adequately from the toxicity and/or complications from the intervention before starting therapy,
• Diagnosis of immunodeficiency (including HIV 1/2 positivity) or currently received systemic steroid therapy with dose superior to 10 mg/day of prednisone or equivalent or any other form of immunosuppressive therapy, within 7 days prior to the first dose of trial treatment,
• Known history of active Bacillus Tuberculosis (TB),
• Hypersensitivity to pembrolizumab or any of its excipients,
• Any contraindication for receiving a treatment of docetaxel, cisplatin, 5-fluorouracil or carboplatin,
• Hearing impairment or cardiorespiratory pathology with a contraindication of overhydration,
• Currently received prophylactic treatment of phenytoin which could have an interaction with cisplatin, 5-fluorouracile or carboplatin or fosphenytoin which could have an interaction with carboplatin,
• Currently received treatment of sorivudine or analogues (e.g. brivudine) with could have an interaction with 5-fluorouracile,
• Complete known dihydropyrimidine dehydrogenase deficiency (DPD),
• Clinically active cardiac disease or myocardial infarction within 6 months prior to the first dose of treatment,
• Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer,

Sponsors & Collaborators

• Centre Antoine Lacassagne: lead
• GORTEC: collaborator
• GERCOR - Multidisciplinary Oncology Cooperative Group: collaborator

Study Sites (1)

PEYRADE Frédéric

Nice, 06000, France

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Radiotherapy; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Therapeutics; Coordination Complexes; Organic Chemicals

Study Officials

• Chrisine LOVERA

  Centre Antoine Lacassagne

  STUDY DIRECTOR

Study Design

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

Model Details: Fluorouracil (F) and pembrolizumab every 21 days followed by radiotherapy (RT) combined with carboplatin in untreated unresectable locally-advanced Head and Neck Squamous Cell Carcinoma (HNSCC).

Study Record Dates

• First Submitted: April 2, 2017
• First Posted: April 14, 2017
• Study Start: March 12, 2019
• Primary Completion: March 12, 2019
• Study Completion: March 12, 2019
• Last Updated: April 8, 2019

Record last verified: 2019-03

Locations

FR (1)