A Phase II Trial of Induction and Maintenance Pembrolizumab and Olaparib in Locally Advanced Head and Neck Squamous Cell Carcinoma
Greg Durm, MD
Primary Investigator
Brief description of study
Detailed description of study
What will happen during the study?
Treatment outcomes are poor for patients with locally advance human papilloma virus (HPV) negative and high-risk HPV positive head and neck squamous cell carcinoma (HNSCC). One standard of care (SOC) for HNSCC is definitive chemoradiotherapy (CRT). This study will evaluate the safety and efficacy of the addition of pembrolizumab, an anti-programmed death-1 (PD1) inhibitor, and olaparib, a Polyadenosine 5'diphosphoribose polymerization (PARP) inhibitor, before and after SOC CRT, which will be delivered in 70 Gray in 35 fractions with concurrent weekly cisplatin 40 mg/m2 over 7 weeks.
Treatment will be offered in three sequential phases. In the induction phase, participants will receive one infusion of pembrolizumab and will take olaparib tablets for a total of 21 days. In the chemoradiation phase, radiation therapy will administered daily (excluding weekends) and cisplatin infusion will be given weekly. In the maintenance phase, pembrolizumab infusion will be done once every 6 weeks in additional to twice daily olaparib tablets for up to 8 treatment cycles that are 42-days per cycle.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Squamous Cell Carcinoma of Head and Neck
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Age: 18 years - 100 years
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Gender: All
Age >18 years on the day of signing the consent
Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
Subject is willing and able to comply with study procedures based on the judgment of the investigator or protocol designee. The subject must be willing to consent to a mandatory pre-study biopsy unless sufficient archival tissue is available.
Biopsy confirmed American Joint Committee on Cancer 8th Edition35 stage III-IV B oral cavity squamous cell carcinoma (SCC), p16-negative oropharyngeal SCC, stage III-IVB hypopharyngeal SCC, stage III-IVB laryngeal SCC -OR- HPV-associated oropharyngeal SCC (p16 positive or HPV-associated) T4 or N3 , T1-3 N2 or T3N0-1 with >10 pack-year tobacco history
At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by imaging (CT/ PET) and is suitable for repeated assessment.
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
No prior curative attempts for this cancer (i.e., surgery, radiation, systemic therapy) and not currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of the study intervention. No evidence of metastatic disease (M0)
Exclusion Criteria
Subjects with prior and concurrent malignancies of different tumor types whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the study drug are eligible with the following exception: Subjects with prior history of HNSCC treated < 3 years to the date of consent.
Cisplatin-ineligible as defined in the protocol.
Severe, active medical comorbidity. Subjects are considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography scan or any psychiatric disorder that prohibits obtaining informed consent.
Subjects unable to swallow orally administered medication prior to initiation of study treatment.
Systemic glucocorticoids for any purpose other than to modulate symptoms from an event of clinical interest of suspected immunologic etiology
