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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03532737
Recruitment Status : Recruiting
First Posted : May 22, 2018
Last Update Posted : September 3, 2020
Information provided by (Responsible Party):
Kuwait Cancer Control Center

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)

Condition or disease Intervention/treatment Phase
Locally Advanced Head and Neck Cancer Drug: Pembrolizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Non-Randomised Controlled Trial Of Concomitant Immune Check Point Inhibitor With Radiotherapy And Chemotherapy Or Cetuximab In Advanced Non Metastatic Head And Neck Cancer
Actual Study Start Date : October 7, 2018
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : October 31, 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Investigational Arm

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
Adding PD-1 inhibitor to the standard of care
Other Name: Keytruda

Primary Outcome Measures :
  1. Dose Limiting Toxicity (DLT) [ Time Frame: From the first dose of pembrolizumab to 28 days after the completion of radiation therapy ]

    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.

  2. Response Rate [ Time Frame: 3 years ]
    Response rates according to irRECIST criteria

Secondary Outcome Measures :
  1. Locoregional control rates [ Time Frame: 5 years ]
    Number of local disease progression events

  2. Progression free survival [ Time Frame: 5 years ]
    Number of local or distant disease progression events

  3. Overall survival [ Time Frame: 5 years initially (longer follow up will be done) ]
    Number of cancer-related deaths

Other Outcome Measures:
  1. Patients' Quality of life (QoL) [ Time Frame: 5 years initially ]
    QoL assessment by the patients

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  • Has history of a diagnosed and/or treated hematologic or primary solid tumor malignancy, unless in remission for at least 5 years prior to randomization
  • Has had previous allogeneic tissue/solid organ transplant
  • Has active infection requiring systemic therapy
  • Has a history of severe hypersensitivity reaction to Pembrolizumab, Cisplatin, cetuximab or radiotherapy or their analogs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03532737

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Contact: Mustafa S El-Sherify, MD +965 554 66285

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Kuwait Cancer Control Center Recruiting
Kuwait, Kuwait
Contact: Mustafa El-Sherify         
Sponsors and Collaborators
Kuwait Cancer Control Center
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Principal Investigator: Mustafa S El-Sherify, MD Kuwait Cancer Control Center
Additional Information:
Kuwait Cancer Registry: Annual Report 2013. Ministry of Health Publications
Thompson LDR. Squamous cell carcinoma variants of the head and neck. Current Diagnostic Pathology (2003) 9, 384 -396

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Responsible Party: Kuwait Cancer Control Center Identifier: NCT03532737    
Other Study ID Numbers: HNIT 01
First Posted: May 22, 2018    Key Record Dates
Last Update Posted: September 3, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Kuwait Cancer Control Center:
head and neck cancer
check point inhibitor
Additional relevant MeSH terms:
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Head and Neck Neoplasms
Neoplasms by Site
Antineoplastic Agents, Immunological
Antineoplastic Agents