Phase Ib Study of Pembrolizumab in Combination With Chemo Radiotherapy (CRT) for Locally-advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Overview
- Phase
- Phase 1
- Intervention
- pembrolizumab (MK-3475)
- Conditions
- Head and Neck Cancer
- Sponsor
- Sanford Health
- Enrollment
- 59
- Locations
- 4
- Primary Endpoint
- Adverse Events Will be Assessed and Graded Using CTCAE 4.0. Occurrences With Max Grade and Percentage/Number of Participants Affected by AEs Will be Provided.
- Status
- Completed
- Last Updated
- 6 months ago
Overview
Brief Summary
This is a single-arm, multi-site, open-label trial of pembrolizumab (MK-3475) used in combination with standard, cisplatin-based, definitive chemoradiotherapy (CRT) in patients with stage III-IVB squamous cell carcinoma of the head and neck (SCCHN). Approximately 39 patients with Stage III-IVB SCCHN will be enrolled to evaluate both the safety and efficacy of this novel combination. Subjects will not be randomized and will all receive the study treatment.
Treatment will consist of a loading dose of pembrolizumab 200 mg IV given 7 days prior to initiation of CRT (day-7). CRT with cisplatin 40 mg/m2 IV weekly and head and neck radiation at 70 Gy fractionated at 2 Gy once daily over 35 days, will begin on day 1. CRT will end on approximately day 46-50. Pembrolizumab 200 mg IV will continue following CRT in an adjuvant fashion starting on day 57 for an additional 5 doses, as tolerated, through day 141. Subjects will be evaluated for response following treatment.
Detailed Description
Each subject will participate in the trial from the time the subject signs the Informed Consent Form (ICF) through the final protocol-specified contact. After a screening phase of 28 days, eligible subjects will receive treatment on Day -7 with a loading dose of the study drug. This will continue during concurrent therapy with cisplatin and radiation, which will begin on day 1. Treatment will continue until completion of therapy, documented confirmed disease progression, unacceptable adverse event(s), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdraws consent, pregnancy of the patient, noncompliance with trial treatment or procedure requirements; or administrative reasons. After the end of treatment, each patient will be followed for 30 days for adverse event monitoring (serious adverse events will be collected for 90 days after the end of treatment or 30 days after the end of treatment if the patient initiates new anticancer therapy, whichever is earlier). Subjects who discontinue for reasons other than disease progression will have post-treatment follow-up for disease status until end of study disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. All subjects will be followed by telephone for overall survival until death, withdrawal of consent, or the Investigator is notified by Sanford Research to discontinue follow-up
Investigators
Eligibility Criteria
Inclusion Criteria
- •Have histologically or cytologically-confirmed head and neck squamous cell carcinoma of the oral cavity (excluding lip), oropharynx, hypopharynx, or larynx.
- •Have TNM clinical stage III, IVA, or IVB disease
- •Be eligible for curative-intent concurrent chemoradiation therapy
- •Be willing and able to provide written informed consent for the trial.
- •Be 18 years of age on day of signing informed consent.
- •Have measurable disease based on RECIST 1.
- •Be willing to provide tissue from a recently obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day -
- •Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from Sanford Research.
- •Have a performance status of 0 or 1 on the ECOG Performance Scale.
- •Demonstrate adequate organ function as defined:
Exclusion Criteria
- •Patients may not be receiving any other investigational agents, chemotherapy, immunotherapy, radiotherapy, or molecular targeted agents within 4 weeks of the start of the study treatment.
- •Prior treatment with radiation to the head and neck
- •Patients with TNM Stage IVC disease
- •Is 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 of the first dose of treatment.
- •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 trial treatment.
- •Has a known history of active TB (Bacillus Tuberculosis)
- •Hypersensitivity to pembrolizumab or any of its excipients.
- •Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- •Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy.
- •Has a 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.
Arms & Interventions
Single Arm
Pembrolizumab + Cisplatin + Radiation
Intervention: pembrolizumab (MK-3475)
Single Arm
Pembrolizumab + Cisplatin + Radiation
Intervention: Cisplatin
Single Arm
Pembrolizumab + Cisplatin + Radiation
Intervention: Radiation
Outcomes
Primary Outcomes
Adverse Events Will be Assessed and Graded Using CTCAE 4.0. Occurrences With Max Grade and Percentage/Number of Participants Affected by AEs Will be Provided.
Time Frame: through day 240 (this time frame allows capturing of AEs that occurred up to 90 days after completion of treatment)
To determine the safety and tolerability of pembrolizumab given in combination with cisplatin-based chemoradiotherapy (CRT) in subjects with treatment naive Stage III-IVB squamous cell carcinoma of the head and neck (SCCHN). Number of participants affected by AEs will be reported by grade and percentage of participants affected. Safety and tolerability will be assessed by clinical review of all relevant parameters including adverse events (AEs), laboratory tests, and vital signs. Count and percentage of AE will be provided.
Secondary Outcomes
- Evaluation of the Efficacy of Pembrolizumab Given in Combination With Definitive CRT by Determining the Number of Participants With Complete Response at Treatment End (Day 150)(Day 150 (post treatment imaging))