Randomized Trial of Loco-regional Radiotherapy Added to Pembrolizumab Alone or With Chemotherapy Versus Systemic Treatment Alone for Patients With Newly Diagnosed Head and Neck Squamous Cell Carcinoma With Synchronous Metastases
Overview
- Phase
- Phase 3
- Intervention
- Pembrolizumab
- Conditions
- Squamous Cell Carcinoma of Head and Neck
- Sponsor
- UNICANCER
- Enrollment
- 102
- Locations
- 26
- Primary Endpoint
- Progression-free survival (PFS)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
Study to evaluate the efficacy of treatment by radiotherapy and pembrolizumab in newly diagnosed metastatic head & neck cancers
Detailed Description
Comparative interventional prospective phase 3, randomised, open-label, multicentric trial comparing the combination of radiotherapy and pembrolizumab alone or with chemotherapy to systemic treatment as first line treatment of patients with newly diagnosed head and neck squamous cell carcinoma with synchronous metastases.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient must have signed a written informed consent form prior to any study specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
- •Histologically confirmed squamous cell carcinoma of head and neck (oral cavity, oropharynx, hypopharynx, and larynx) including unknown primary head and neck lymph nodes with distant metastases at presentation (T1-4 N0-3 M1). Histological confirmation is required in case of a single metastatic lesion.
- •Eligible for treatment by pembrolizumab according to the European Marketing Authorization
- •Patient ≥18 years old
- •Performance status: 0-1 (WHO)
- •Combined Positive Score (CPS) ≥1 for primary tumor (as determined per local practice)
- •Subjects must have at least one measurable lesion as per RECIST v1.1 to assess efficacy
- •Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to randomization:
- •a. If randomization is done before treatment start: i. Absolute neutrophil count ≥1.5 × 10⁹/L ii. Platelet ≥100 × 10⁹/L iii. Hemoglobin ≥90 g/L iv. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT), ≤3 × upper limit of normal (ULN), (unless documented liver metastases where ≤5 x ULN is permitted) v. Bilirubin ≤1.5 × ULN. vi. Serum albumin ≥25 g/L vii. Creatinine clearance ≥30 mL/min (calculated per institutional guidelines or by Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formula) viii. Corrected serum calcium of ≤11.5 mg/dL or ≤2.6 mmol/L. b. If randomization if done after treatment start i. Absolute neutrophil count ≥1.0 × 10⁹/L ii. Platelet ≥75 × 10⁹/L iii. Hemoglobin ≥85 g/L
- •Patient must agree to use adequate contraception methods for the duration of the study treatment and up to 4 months after the last dose of pembrolizumab administration
Exclusion Criteria
- •Symptomatic central nervous system (CNS) metastases and / or carcinomatous meningitis
- •History of another malignancy within 2 years prior to study inclusion, with the exception of completely resected basal or squamous cell skin cancer, or successfully treated in-situ carcinoma
- •Prior radiotherapy in the head and neck region
- •Any prior or current non-surgical treatment for invasive head and neck cancer. (except for pembrolizumab +/- chemotherapy for the current cancer for a maximum of 6 cycles). This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, chemotherapy, anti-PD-1/PD-L1 and CTLA-4, prior radiotherapy (RT), or use of any investigational agent. Loco-regional recurrent or second primary head and neck cancer after prior surgical treatment alone in the head and neck region could be eligible.
- •Known Acquired Immune Deficiency Syndrome (AIDS)
- •Known currently active infection including hepatitis B or hepatitis C
- •Patient having received live attenuated vaccine within 28 days prior to enrolment
- •Pregnant or breast feeding woman
- •Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized with hormonal substitution, or psoriasis which do not require systemic treatment
- •Active immunodeficiency or ongoing immunosuppressive therapy
Arms & Interventions
Radiotherapy added to systemic treatment
Pembrolizumab 200mg every 3 weeks until disease progression or unacceptable toxicity. Loco-regional radiotherapy(RT) depending on the RT timing : * Before 3 cycles of pembrolizumab: RT could start at any time between one week after the first administration of pembrolizumab and the first day of the 3rd cycle. * After 3 cycles of pembrolizumab: RT could start at any time after 3rd cycle and up to a maximum of 4 weeks after the 6th cycle of pembrolizumab. If the investigator decides before randomization to add chemotherapy and depending on the RT timing: * Start of RT planned before 3rd cycle: Chemotherapy could be delayed after the end of RT and start from cycle 3 or 4 of pembrolizumab. * RT planned after 3rd cycle: Chemotherapy should start at the same time of pembrolizumab. Chemotherapy will be composed of carboplatin AUC 5 mg/mL/min or cisplatin 100 mg/m² every 3 weeks with 5-fluorouracil (5-FU) 1000mg/m²/day during 4 days every 3 weeks for a maximum of 6 cycles
Intervention: Pembrolizumab
Radiotherapy added to systemic treatment
Pembrolizumab 200mg every 3 weeks until disease progression or unacceptable toxicity. Loco-regional radiotherapy(RT) depending on the RT timing : * Before 3 cycles of pembrolizumab: RT could start at any time between one week after the first administration of pembrolizumab and the first day of the 3rd cycle. * After 3 cycles of pembrolizumab: RT could start at any time after 3rd cycle and up to a maximum of 4 weeks after the 6th cycle of pembrolizumab. If the investigator decides before randomization to add chemotherapy and depending on the RT timing: * Start of RT planned before 3rd cycle: Chemotherapy could be delayed after the end of RT and start from cycle 3 or 4 of pembrolizumab. * RT planned after 3rd cycle: Chemotherapy should start at the same time of pembrolizumab. Chemotherapy will be composed of carboplatin AUC 5 mg/mL/min or cisplatin 100 mg/m² every 3 weeks with 5-fluorouracil (5-FU) 1000mg/m²/day during 4 days every 3 weeks for a maximum of 6 cycles
Intervention: Loco-regional radiotherapy
Radiotherapy added to systemic treatment
Pembrolizumab 200mg every 3 weeks until disease progression or unacceptable toxicity. Loco-regional radiotherapy(RT) depending on the RT timing : * Before 3 cycles of pembrolizumab: RT could start at any time between one week after the first administration of pembrolizumab and the first day of the 3rd cycle. * After 3 cycles of pembrolizumab: RT could start at any time after 3rd cycle and up to a maximum of 4 weeks after the 6th cycle of pembrolizumab. If the investigator decides before randomization to add chemotherapy and depending on the RT timing: * Start of RT planned before 3rd cycle: Chemotherapy could be delayed after the end of RT and start from cycle 3 or 4 of pembrolizumab. * RT planned after 3rd cycle: Chemotherapy should start at the same time of pembrolizumab. Chemotherapy will be composed of carboplatin AUC 5 mg/mL/min or cisplatin 100 mg/m² every 3 weeks with 5-fluorouracil (5-FU) 1000mg/m²/day during 4 days every 3 weeks for a maximum of 6 cycles
Intervention: Chemotherapy
Systemic treatment
Pembrolizumab 200 mg every 3 weeks until disease progression or unacceptable toxicity. If the investigator decides before randomization to add chemotherapy with pembrolizumab, the chemotherapy will be composed of carboplatin area under the curve (AUC) 5 mg/mL/min or cisplatin 100 mg/m² every 3 weeks with 5-FU 1000 mg/m²/day during 4 days every 3 weeks for a maximum of 6 cycles
Intervention: Pembrolizumab
Systemic treatment
Pembrolizumab 200 mg every 3 weeks until disease progression or unacceptable toxicity. If the investigator decides before randomization to add chemotherapy with pembrolizumab, the chemotherapy will be composed of carboplatin area under the curve (AUC) 5 mg/mL/min or cisplatin 100 mg/m² every 3 weeks with 5-FU 1000 mg/m²/day during 4 days every 3 weeks for a maximum of 6 cycles
Intervention: Chemotherapy
Outcomes
Primary Outcomes
Progression-free survival (PFS)
Time Frame: From randomization to disease progression or death, up to 3 years.
The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.
Secondary Outcomes
- Overall survival (OS)(From randomization to death from any cause, up to 5 years.)
- Quality of life questionnaire - Core 30 (QLQ-C30)(At baseline, 4 months, 6 months, 12 months, 18 months, 2 years, 3 years, and 4 years)
- Quality of Life Questionnaire - Head & Neck Cancer Module (QLQ-H&N35)(At baseline, 4 months, 6 months, 12 months, 18 months, 2 years, 3 years, and 4 years)
- Objective response rate (ORR)(At 18 weeks and 27 weeks)
- Loco-regional progression(From randomization to loco-regional progression, up to 5 years.)
- Distant progression(From randomization to distant progression, up to 5 years.)
- Progression-free survival 2 (PFS2)(Up to 5 years after randomization.)
- Incidence of Treatment Adverse Events(Throughout study completion, up to 5 years.)
- Compliance to treatment(Throughout study treatment, up to 5 years)