Dosing Study of Radiation Combined With Tislelizumab and Pamiparib in Patients With Previously Treated Head and Neck Cancer
A Phase I Trial of Re-Irradiation With Concurrent Chemotherapy in Combination With Tislelizumab and Pamiparib in Patients With Previously Treated Head and Neck Squamous Cell Carcinoma
1 other identifier
interventional
30
1 country
1
Brief Summary
The purpose of this study is to evaluate the safety, tolerability and maximum tolerated dose of tislelizumab in combination with pamiparib plus chemoradiotherapy (chemotherapy and radiation) in individuals with recurrent head and neck cancer, which means that the person's cancer has come back after treatment. Participation in the study should last for about 15 months while participants receive tislelizumab and chemoradiotherapy with pamiparib. Afterwards, they will return to the clinic for follow up every 4 months for 2 years, every 6 month for the next 2 years, and then once a year for the rest of their life.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 head-and-neck-cancer
Started Mar 2023
Typical duration for phase_1 head-and-neck-cancer
1 active site
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
August 31, 2022
CompletedFirst Posted
Study publicly available on registry
September 2, 2022
CompletedStudy Start
First participant enrolled
March 7, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2028
March 4, 2026
March 1, 2026
4.8 years
August 31, 2022
March 2, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maximum Tolerated Dose/Recommended Phase 2 Dose of Pamiparib in Combination with 5 Fluorouracil-Hydroxea (FHX) and Tislelizumab
Determine the maximally tolerated dose (MTD)/ recommended phase 2 dose (RP2D) for pamiparib in combination with FHX and tislelizumab in subjects with recurrent head and neck squamous cell carcinoma (HNSCC) as assessed by the incidence of dose-limiting toxicities (side effects) reported among study participants. Dose-limiting toxicities will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.
15 months
Secondary Outcomes (2)
Progression Free Survival of Participants Receiving Pamiparib in Combination with 5 Fluorouracil-Hydroxea (FHX) and Tislelizumab
15 months
Overall Free Survival of Participants Receiving Pamiparib in Combination with 5 Fluorouracil-Hydroxea (FHX) and Tislelizumab
15 months
Study Arms (4)
Dose-Finding Group 1: Dose Level 1 (Part 1 of Study)
EXPERIMENTALThe purpose of part 1 is to determine the best tolerated dose of study drugs with the least side effects. Dose escalation means that some participants will receive a different (higher) dose than other participants depending on when they join the study. This is to determine side effects at different doses and find a dose that will be safe to give to all participants. Participants in this group will receive: 1. One dose of tislelizumab (200 mg) 15 days before chemoradiotherapy (CRT) given intravenously (by IV), which means through a vein. 2. Chemoradiotherapy over a period of 5 weeks. During each cycle of CRT, participants will receive: * Pamiparib (20 mg daily on days 0-5 of each cycle) along with 5FU and hydroxyurea for 5 days. * Radiation will also be given two times a day for 5 days 3. After CRT, participants will rest for roughly 8 days without study drugs or radiation then they will receive tislelizumab (200 mg) for 12 months by IV over 30 minutes every 6 weeks.
Dose-Finding Group 2: Dose Level 2 (Part 1 of Study)
EXPERIMENTALThe purpose of part 1 is to determine the best tolerated dose of study drugs with the least side effects. Dose escalation means that some participants will receive a different (higher) dose than other participants depending on when they join the study. This is to determine side effects at different doses and find a dose that will be safe to give to all participants. Participants in this group will receive: 1. One dose of tislelizumab (200 mg) 15 days before chemoradiotherapy (CRT) given intravenously (by IV), which means through a vein. 2. Chemoradiotherapy over a period of 5 weeks. During each cycle of CRT, participants will receive: * Pamiparib (20 mg twice daily on days 0-5 of each 14 -day cycle) along with 5FU and hydroxyurea for 5 days. * Radiation will also be given two times a day for 5 days 3. After CRT, participants will rest for roughly 8 days without study drugs or radiation then they will receive tislelizumab (200 mg) for 12 months by IV over 30 minutes every 6 weeks.
Dose-Finding Group 3: Dose Level 3 (Part 1 of Study)
EXPERIMENTALThe purpose of part 1 is to determine the best tolerated dose of study drugs with the least side effects. Dose escalation means that some participants will receive a different (higher) dose than other participants depending on when they join the study. This is to determine side effects at different doses and find a dose that will be safe to give to all participants. Participants in this group will receive: 1. One dose of tislelizumab (200 mg) 15 days before chemoradiotherapy (CRT) given intravenously (by IV), which means through a vein. 2. Chemoradiotherapy over a period of 5 weeks. During each cycle of CRT, participants will receive: * Pamiparib (40 mg twice daily on days 0-5 of each 14 -day cycle) along with 5FU and hydroxyurea for 5 days. * Radiation will also be given two times a day for 5 days 3. After CRT, participants will rest for roughly 8 days without study drugs or radiation then they will receive tislelizumab (200 mg) for 12 months by IV over 30 minutes every 6 weeks.
Dose Expansion Group ( Part II of Study)
EXPERIMENTALPart 2 (dose expansion phase): The purpose of this part is to continue to evaluate the dose of study drugs that is the best tolerated and has the least side effects. This part will start once the dose is selected from part 1. Enrollment in this part of the study is dependent on when participants join the study. Approximately 18 subjects will be enrolled in Part 2.
Interventions
A combination of chemotherapy and radiation given at the same time to treat cancer.
An anti-cancer drug that targets specific cells to help fight cancer given by IV (through a needle inserted into a vein).
A chemotherapy drug given in pill form; used to treat leukemia and head and neck cancer.
A chemotherapy drug used to treat different types of cancer.
An anti-cancer drug.
Eligibility Criteria
You may qualify if:
- Clinically documented recurrent head and neck cancer requiring regional therapy.
- Human papillomavirus (HPV) testing for oropharynx primary tumors by p16 immunohistochemistry (IHC) positivity
- Availability of more than (or equal to) 10 unstained 5 micron slides (to be provided to Human Tissue Resource Center at the University of Chicago). Subjects who cannot fulfill this requirement will need to undergo a new biopsy prior to enrollment on study.
- Recurrent or second primary, previously irradiated head and neck squamous cell carcinoma without clinically measurably distant metastatic disease, or low volume oligometastatic disease amenable to Stereotactic Body Radiation Therapy (SBRT) or other curative-intent therapy (e.g. surgery, radiation frequency ablation therapy)
- Prior radiation therapy completed in 4 months (or longer) , and/or chemotherapy, immunotherapy, or targeted therapy completed 1 month (or earlier) before study entry, and patient should have recovered from any adverse effects.
- Prior programmed death-1 (PD-1)/ programmed death ligand-1 (PD-L1) inhibition is permitted.
- Prior chemotherapy is permitted.
- Patients who undergo surgical salvage therapy with positive margin or extranodal extension or other high-risk patients determined during multidisciplinary tumor board who are eligible for adjuvant re-irradiation therapy are eligible.
- years of age and older.
- Eastern Cooperative Oncology Group performance status of one or less.
- Life expectancy of greater than 12 weeks.
- Negative serum or urine pregnancy test at screening for patients of childbearing potential.
- Patients must have normal organ and marrow functions as defined by lab values that will be confirmed by the study doctor.
- Age, Sex, and Reproductive Status:
- Women of childbearing potential (WOCBP=premenopausal woman capable of becoming pregnant) must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug.
- +7 more criteria
You may not qualify if:
- Previously untreated patients with locoregional-only disease are not eligible.
- Patients who have had chemotherapy within 4 weeks prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical composition or excipients used in the study.
- Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of study drug(s).
- Note: Patients who are currently or have recently been on any of the following corticosteroid regimens are not excluded:
- Adrenal replacement corticosteroid (dose ≤ 10 mg daily of prednisone or equivalent)
- Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption
- Short course (≤ 7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a nonautoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen)
- Has hypersensitivity to tislelizumab, pamiparib, or any other drug used in this protocol.
- Has a known history of active tuberculosis (Bacillus Tuberculosis infection)
- 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 or any tumors that are not likely to influence live expectancy in the subsequent 3 years without active treatment (e.g. low grade prostate cancer in absence of therapy), or prior history of acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS).
- Has active autoimmune disease that has required systemic treatment in the past year (i.e. with use of steroids or immunosuppressive drugs). Replacement therapy e.g. levothyroxine, insulin, or physiologic corticosteroid doses for adrenal or pituitary insufficiency, etc. are not considered a form of systemic treatment.
- Has known history of, or any evidence of active interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases including pulmonary fibrosis, or acute lung diseases.
- Has a history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
The University of Chicago
Chicago, Illinois, 60637, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ari Rosenberg, MD
University of Chicago
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 31, 2022
First Posted
September 2, 2022
Study Start
March 7, 2023
Primary Completion (Estimated)
January 1, 2028
Study Completion (Estimated)
January 1, 2028
Last Updated
March 4, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share