Pembrolizumab Plus Olaparib in LA-HNSCC
A Phase II Trial of Induction and Maintenance Pembrolizumab and Olaparib in Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)
1 other identifier
interventional
45
1 country
4
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Sep 2022
Longer than P75 for phase_2
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 4, 2022
CompletedFirst Posted
Study publicly available on registry
May 9, 2022
CompletedStudy Start
First participant enrolled
September 2, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 21, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 21, 2030
January 28, 2026
January 1, 2026
4.4 years
May 4, 2022
January 26, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
One Year Progression Free Survival (PFS)
One Year PFS will be defined as the period from the date of treatment start until disease progression or death (whichever occurs first) up to one year. Subjects who have not had an event will be censored at the date of last disease assessment documenting the subject was free of progression. Progression will be evaluated by RECIST v1.1 RECIST v.1.1: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
up to 1 year from start of treatment
Secondary Outcomes (11)
Overall survival
up to 2 years from start of treatment
Two Year Progression Free Survival (PFS)
Up to 2 years from start of treatment
Induction therapy related delays in chemoradiation therapy
Up to 14 weeks from start of treatment
Toxicities related to maintenance therapy
Up to 2 years from start of treatment
Induction related toxicity using patient-reported outcomes
Up to 2 years from start of treatment
- +6 more secondary outcomes
Study Arms (1)
Single Arm
EXPERIMENTALThe participants will receive neoadjuvant and adjuvant pembrolizumab and olaparib combination plus standard of care (chemoradiation therapy) as defined in the protocol.
Interventions
In the induction phase, participants will receive a single intravenous infusion of pembrolizumab 400 mg prior to chemoradiotherapy. In the Maintenance Phase, participants will receive pembrolizumab 400 mg every 42 days for 8 cycles.
In the chemoradiation phase, participants will receive 70 Gray external beam radiotherapy, at 2 Gray/fraction dose, 35 fractions, delivered once a day, on weekdays, using Intensity Modulated Radiotherapy Treatments or proton radiotherapy techniques, over 7 weeks.
In the induction phase, participants will receive daily oral olaparib 150 mg two times a day for 3 weeks prior to chemoradiotherapy. In the Maintenance Phase, participants will receive daily olaparib 150 mg two times a day for up to 48 weeks.
In the chemoradiation phase, participants will receive weekly intravenous cisplatin infusion, 40 mg/m2 over 7 weeks. In the chemoradiation phase, standard of care radiation therapy and chemotherapy will be administered, for a total of 7 weeks. Radiation therapy is done on daily basis (excluding weekends), and chemotherapy therapy will involve cisplatin infusion once weekly.
Eligibility Criteria
You may qualify if:
- In order to participate in this study, a subject must meet all of the eligibility criteria outlined below.
- 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)
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
Indiana University Simon Comprehensive Cancer Center
Indianapolis, Indiana, 46202, United States
University of Louisville, Brown Cancer Center
Louisville, Kentucky, 40202, United States
UNC Lineberger
Chapel Hill, North Carolina, 27514, United States
Medical University of South Carolina (MUSC)
Charleston, South Carolina, 29425, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Siddharth Sheth, DO MPH
UNC Lineberger Comprehensive Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 4, 2022
First Posted
May 9, 2022
Study Start
September 2, 2022
Primary Completion (Estimated)
January 21, 2027
Study Completion (Estimated)
November 21, 2030
Last Updated
January 28, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will not share