Clinical trial NCT02609503: Pembrolizumab + Radiation for Locally Adv SCC of the Head and Neck (SCCHN) Not Eligible Cisplatin
Official title: Pembrolizumab and Radiation for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN) Not Eligible for Cisplatin Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2015-11-20
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is being done to evaluate the efficacy of Pembrolizumab, concomitant with and following standard of care definitive radiation, for locally advanced squamous cell carcinoma of the head and neck patients who are not good candidates for Cisplatin.

Detailed description: This open label, phase II trial will enroll 29 subjects in order to evaluate the efficacy of Pembrolizumab, concomitant with and following standard of care definitive radiation for locally advanced squamous cell carcinoma head and neck patients who are not good candidates for Cisplatin. Objectives include estimating progression free survival and overall survival, response rates, safety and toxicity, and quality of life in these patients. Correlative studies, based on serial blood collections and tumor samples, may be done under a separate protocol based on availability of archival diagnostic tissue.

Eligibility criteria: Inclusion Criteria:

* Be willing and able to provide written informed consent/assent for the trial
* Be greater than or equal to 18 years of age
* Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 1
* Histologically or cytologically confirmed stage III-IV (non-metastatic) squamous cell carcinoma of the head and neck as defined by American Joint Committee on Cancer. Nasopharyngeal cancer patients will be excluded.
* Ineligible for high dose cisplatin therapy; the reason for ineligibility must be defined.
* Demonstrate adequate organ function. All screening labs should be performed within 14 days of treatment initiation.
* No prior curative attempts for this cancer (i.e., surgery, radiation and/or other).
* Female patients of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. Serum pregnancy test may be required.
* Female patients 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 120 days after the last dose of study medication.
* Male patients should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
* As determined by the enrolling physician or protocol designee, ability of the patient to understand and comply with study procedures for the entire length of the study.
* Consent for the use of any residual material from biopsy (archival tissue) and serial blood draws will be required for enrollment.

Exclusion Criteria:

* If currently participating in or has participated in a study of an investigational agent or using 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 had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier
* Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered from adverse events due to a previously administered agent.
* Has a known additional malignancy that is metastatic, progressing or requires active treatment.
* Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease even if resolved; patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule.
* Has clinical or radiologic evidence of interstitial lung disease or active, non-infectious pneumonitis
* Has an active infection requiring systemic therapy.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Has inadequate home environment or social support to safely complete the trial procedures.
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
* Has received prior therapy with an anti-programmed cell death (PD-1), anti-PD-L1, anti-PD-L1, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody.
* Has a known history of Human Immunodeficiency Virus (HIV) HIV 1/2 antibodies) Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C )e.g., HCV RNA \[qualitative\] is detected).
* Has received a live vaccine within 30 days prior to the first dose of trial treatment.
* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis

Primary outcomes:
measure: 20 Week Progression Free Survival Rate
timeFrame: 20 weeks after D1 of treatment
measure: One Year Progression Free Survival Rate
timeFrame: 1 years after D1 of treatment
measure: Two Year Progression Free Survival Rate
timeFrame: 2 years after D1 of treatment
measure: Median Progression Free Survival
timeFrame: up to 5 years after D1 of treatment
Secondary outcomes:
measure: One Year Overall Survival Rate
timeFrame: 1 year after Day 1 of treatment
measure: Two Year Overall Survival Rate
timeFrame: 2 years after Day 1 of treatment
measure: Proportion of Participants Who Received <95% of Intended Dose of Radiation
timeFrame: 7 weeks
measure: Number of Participants With Clinically Relevant Adverse Events
timeFrame: Monitored continuously from D1 of treatment through 40 weeks.
measure: Overall Response Rate
timeFrame: 2 years after start of treatment
measure: Complete Response Rate
timeFrame: 2 years after start of treatment
measure: Five Years Locoregional Recurrence Rate
timeFrame: 5 years from start of treatment
measure: Five Years Distant Metastasis Rate
timeFrame: 5 years from start of treatment
measure: Quality of Life Measured by Functional Assessment of Cancer Therapy - Head and Neck (FACT-HN)
timeFrame: At baseline, 10 and 20 weeks after initiation of treatment
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: John Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Jared Weiss, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weiss J, Sheth S, Deal AM, Grilley Olson JE, Patel S, Hackman TG, Blumberg JM, Galloway TJ, Patel S, Zanation AM, Shen CJ, Hayes DN, Hilliard C, Mehra R, McKinnon KP, Wang HH, Weissler MC, Bauman JR, Chera BS, Vincent BG. Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. Clin Cancer Res. 2020 Aug 15;26(16):4260-4267. doi: 10.1158/1078-0432.CCR-20-0230. Epub 2020 May 5.