Clinical trial NCT05366166: Pembrolizumab Plus Olaparib in LA-HNSCC
Official title: A Phase II Trial of Induction and Maintenance Pembrolizumab and Olaparib in Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of Head and Neck
Keywords: head and neck
squamous cell carcinoma
HPV negative
pembrolizumab
olaparib
PARP inhibitor
anti-PD1 inhibitor
intensity modulation radiation therapy
Proton therapy
cisplatin
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2022-05-09
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to evaluate the effectiveness of using a combination of pembrolizumab and olaparib when given before and after standard chemoradiation therapy in treating locally advanced head and neck squamous cell carcinoma. Pembrolizumab and olaparib are drugs that are approved for head and neck cancer treatment. However, FDA has not approved the use of these two drugs together in treating head and neck cancer.

Detailed description: 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 criteria: Inclusion Criteria:

In order to participate in this study, a subject must meet all of the eligibility criteria outlined below.

1. Age \>18 years on the day of signing the consent
2. Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
3. 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.
4. 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
5. 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.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
7. 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

1. 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.
2. Cisplatin-ineligible as defined in the protocol.
3. 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.
4. Subjects unable to swallow orally administered medication prior to initiation of study treatment.
5. Systemic glucocorticoids for any purpose other than to modulate symptoms from an event of clinical interest of suspected immunologic etiology

Primary outcomes:
measure: One Year Progression Free Survival (PFS)
timeFrame: up to 1 year from start of treatment
Secondary outcomes:
measure: Overall survival
timeFrame: up to 2 years from start of treatment
measure: Two Year Progression Free Survival (PFS)
timeFrame: Up to 2 years from start of treatment
measure: Induction therapy related delays in chemoradiation therapy
timeFrame: Up to 14 weeks from start of treatment
measure: Toxicities related to maintenance therapy
timeFrame: Up to 2 years from start of treatment
measure: Induction related toxicity using patient-reported outcomes
timeFrame: Up to 2 years from start of treatment
measure: Patient reported maintenance therapy-related toxicities
timeFrame: Up to 2 years from start of treatment
measure: One-year locoregional control
timeFrame: Up to 1 year from start of treatment
measure: Distant Metastasis-Free Survival (DMFS)
timeFrame: Up to 1 year from start of treatment
measure: Correlate Combined Positive Score (CPS) and one-year progression free survival (PFS)
timeFrame: Up to 1 year
measure: Head and Neck Cancer Associated Patient Reported Outcomes (PRO)
timeFrame: Baseline, 4week, 7 week, 12 weeks, 6months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months
measure: General Cancer Associated Patient Reported Outcomes (PRO)
timeFrame: Baseline, 4week, 7week, 12 weeks, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, 60 months
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Simon Comprehensive Cancer Center
state: Indiana
city: Louisville
country: United States
facility: University of Louisville, Brown Cancer Center
state: Kentucky
city: Chapel Hill
country: United States
facility: UNC Lineberger
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Siddharth Sheth, DO MPH
role: PRINCIPAL_INVESTIGATOR
References: