Concomitant Immune Check Point Inhibitor With Radiochemotherapy in Head And Neck Cancer

NCT03532737 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: HNIT 01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Locally advanced head and neck cancer (HNC) is a challenge as, in spite of initial good control with chemoradiation, the majority of patients fails systemically. In the last 2 years, immune check points inhibitors (mainly Programmed Death (PD)-1 inhibitors) were approved for metastatic/recurrent HNC. The favorable toxicity profile and durable responses was the main benefit of these drugs along the scope of cancers they were approved for. Aim of the study and methods: This will be a phase II non-randomized trial to define safety and efficacy of combining the PD-1 inhibitor pembrolizumab given concomitantly with the usual standard of care chemoradiation/bioradiation for locally advanced non-nasopharyngeal HNC. Primary end point will be assessment of toxicity and tolerability while the secondary end points will be response rates (RR) and progression free survival (PFS)

Conditions

Locally Advanced Head and Neck Cancer

Keywords

head and neck cancer; check point inhibitor; Pembrolizumab; Chemoradiation

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity (DLT)

  A pembrolizumab attributable, dose-limiting toxicity (DLT) will be defined as follows: 1\) Any ≥ grade 3 adverse event (CTCAE, v. 4) that is related to pembrolizumab that does not resolve to grade 1 or less within 28 days; 2) A delay in radiotherapy of \> 2 weeks due to toxicity related to pembrolizumab; 3) Inability to complete radiotherapy due to toxicity related to pembrolizumab; 4) Inability to receive an adequate dose (≥ 70%) of cisplatin or cetuximab due to toxicity definitely related to pembrolizumab.

  From the first dose of pembrolizumab to 28 days after the completion of radiation therapy

• Response Rate

  Response rates according to irRECIST criteria

  3 years

Secondary Outcomes (3)

• Locoregional control rates

  5 years

• Progression free survival

  5 years

• Overall survival

  5 years initially (longer follow up will be done)

Other Outcomes (1)

• Patients' Quality of life (QoL)

  5 years initially

Study Arms (1)

Investigational Arm

EXPERIMENTAL

All patients will receive radical chemoradiation in addition to the investigational concomitant check point inhibitor CHEMOTHERAPY: Cisplatin: 100 mg/m2 Q21d D1, D22, D43. OR Cetuximab Loading dose 400 mg/m², one week before radiation then maintenance dose 250 mg/m² weekly, D8, D15, D22, D29, D36, D43. PD-1 inhibitor: Pembrolizumab 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks 21 days prior to radiation, then Day 1 of radiation and then every 21 days for total 6 doses Intensity modulated radiotherapy (IMRT) techniques will be used. A total dose of 66-70 Gy/ 30-35 Fr over 6-7 weeks will be delivered to the primary site and draining lymphatics using simultaneous Integrated Boost (SIB).

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Adding PD-1 inhibitor to the standard of care

Also known as: Keytruda

Investigational Arm

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient has pathologically proven squamous cell carcinoma arising in the oropharynx, hypopharynx, oral cavity, or larynx
• The patient has stage III or IVA disease with an expected survival of 12 months.
• The patient is medically suitable to withstand a course of definitive radiation therapy \& chemotherapy.
• Karnofsky performance status is \> 60.
• The patient must have achieved lawful age to provide informed consent according to local or national law .
• Laboratory values performed within 14 days prior to concurrent chemotherapy should be as follows:
• i) Absolute neutrophil count (ANC) ≥ 2000/mm ii) Platelet count ≥ 100.000/mm iii) Hemoglobin ≥ 10g/dl or 100g/L iv) Urea and serum creatinine ≤ 1.5 mg/dl. (for cisplatin) v) Creatinine clearance ≥ 50 ml/min. (for cisplatin) vi) serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) ≤ 2 × upper limit of laboratory normal vii) Serum calcium within normal limits.
• Has provided tissue for Programmed Cell Death Receptor Ligand 1 (PD-L1) biomarker analysis from a core or excisional biopsy
• Has evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography scan or magnetic resonance imaging, based on RECIST version 1.1
• Is eligible for definitive chemoradiation (CRT) and not considered for primary surgery based on investigator decision
• Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy
• Female and male participants of reproductive potential must agree to use adequate contraception throughout the study period and for up to 180 days after the last dose of study therapy

You may not qualify if:

• The patient has evidence of distant metastatic disease.
• The patient has received prior systemic chemotherapy within the last three years.
• The patient has undergone previous surgery for the tumor, other than biopsy.
• The patient has received prior radiation therapy to the H\&N.
• The patient's radiation therapy is considered to be a part of a postoperative regimen following primary surgical resection.
• The patient is pregnant or breast feeding.
• The patient has a medical (e.g. renal impairment) or psychological condition that would not permit the patient to complete the trial or sign informed consent.
• Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), anti-PD-L1, anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in clinical studies with immunotherapy
• Has received a live vaccine within 30 days prior to the first dose of study therapy
• Has not recovered from major surgery prior to starting study therapy
• Has known active Hepatitis B or C
• Has known history of Human Immunodeficiency Virus (HIV)
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.

Sponsors & Collaborators

• Kuwait Cancer Control Center: lead

Study Sites (1)

Kuwait Cancer Control Center

Kuwait City, Kuwait

RECRUITING

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Related Links

• Cancer Research UK. Accessed \[January\] \[2018\]
• Kulkarni MR. Head and neck cancer Burden in India. Internat J of Head and Neck Surg. 2013; 4 (1): 29-35
• The Gulf Federation for Cancer Control Guidelines. Last Accessed August 2020
• NCCN Clinical Practice Guidelines in Oncology. Head and Neck. In NCCN Guidelines, Version 1.2018 Edition 2018
• Clinical Trials Protocols. Accessed Feb 2018
• Clinical Trials Protocols. Accessed Feb 2018
• Clinical Trials Protocols. Accessed Feb 2018
• Clinical Trials Protocols. Accessed Feb 2018
• Clinical Trials Protocols. Accessed Feb 2018
• Clinical Trials Protocols. Accessed Feb 2018

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Study Officials

• Mustafa S El-Sherify, MD

  Kuwait Cancer Control Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mustafa S El-Sherify, MD

CONTACT

+965 554 66285; mustafashawki@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2018
• First Posted: May 22, 2018
• Study Start: October 7, 2018
• Primary Completion: September 30, 2025
• Study Completion: October 31, 2025
• Last Updated: January 23, 2024

Record last verified: 2024-01

Locations

KU (1)