Head and Neck CancerPhase 1NCT05526924
Dosing Study of Radiation Combined With Tislelizumab and Pamiparib in Patients With Previously Treated Head and Neck Cancer
A Phase 1 study testing Chemoradiation, Pamiparib and Hydroxyurea in people with Head and Neck Cancer and Head and Neck Squamous Cell Carcinoma, run by University of Chicago at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma, Head and Neck Carcinoma
- What is being tested?
- Chemoradiation, Pamiparib and Hydroxyurea
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Mar 2023to 1 Jan 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 22Show fewer
- 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.
- 18 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.
- Women must not be breastfeeding.
- WOCBP must agree to follow instructions for highly effective method(s) of contraception for the duration of treatment and for 180 days (6 months) after the last dose of study drug(s).
- Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 180 days (6 months) after the last dose of study drug(s).
- Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. Females must still undergo pregnancy testing as described in this section.
- Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of <1% when used consistently and correctly.
- At a minimum subjects must agree to the use of one method of highly effective contraception as listed in Appendix D. In addition, male subjects are expected to use a condom as noted in Appendix D. The effects of tislelizumab and pamiparib on the developing human fetus are unknown. For this reason and because monoclonal antibodies and PARP inhibitor agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of pamiparib and tislelizumab administration.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- • 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:
Show all 25Show fewer
- 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).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). However, if eradicated subject is eligible.
- Has received a live vaccine within 28 days of planned start of study therapy.
- o Note: Vaccines for COVID-19 are allowed except for any live vaccine that may be developed. Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed within 28 days prior to initiation of treatment. Vaccines should not be given during the chemo-radiation phase until marrow function has normalized as vaccines may not be efficacious during periods of marrow suppression.
- Uncontrolled intercurrent illness including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Patients receiving any medications or substances that are known to be strong CYP3A inducers (eg. avasimibe, carbamazepine, mitotane, phenobarbital, phenytoin, rifabutin, rifampin/ rifampicin) are ineligible. Patients receiving herbal remedies/medicines such as St. John's Wort (Hypericum perforatum) are also ineligible. See Sections 5.5.2 and 5.5.3 for prohibited medications on study.
- Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
- Pregnant women are excluded from this study because pamiparib is a PARP inhibitor and tislelizumab is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pamiparib and tislelizumab, breastfeeding should be discontinued if the mother is treated with pamiparib and tislelizumab.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pamiparib and tislelizumab. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
- Disease/procedure significantly affecting gastrointestinal function, such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or gastrointestinal perforation or fistulae. Note: Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed (assuming no drug interaction potential).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
The University of Chicago
Chicago, Illinois, 60637
Cancer Clinical Trials Office, 855-702-8222, cancerclinicaltrials@bsd.uchicago.edu
About this study
Official title: 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
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.
Read the detailed description
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.
During the study, participants will first receive one dose of tislelziumab. Tislelzumab is an experimental drug, meaning, it is not approved by the U.S. Food and Drug Administration (FDA) to treat cancer. Next, participants will receive pamiparib in combination with CRT (chemotherapy and radiation). Pamiparib is also an experimental drug and not approved by the FDA.
Chemoradiotherapy will consist of chemotherapy drugs, 5-FU and hydroxyurea, plus radiation therapy. 5-FU is approved by the FDA to treat many types of cancer such as colon cancer but has not been approved for the treatment of head and neck cancer. Its use is experimental in this study. Hydroxyurea is approved by the FDA to treat many types of cancer, including in combination with radiation therapy for the local control of squamous carcinoma of the head and neck. The combination of tislelizumab, hydroxyurea with 5-FU, radiation, and pamiparib, is considered experimental in this study.
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.
- Conditions
- Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma, Head and Neck Carcinoma, Head and Neck Cancer Stage IV, Head and Neck Cancers - Throat
- Being tested
- Chemoradiation, Pamiparib, Hydroxyurea, Fluorouracil (5FU), Tislelizumab
- Keywords
- head and neck cancer, head and neck carcinoma, Head and Neck Squamous Cell Carcinoma, throat cancer, HNSCC treatment
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChemoradiationRadiation
A combination of chemotherapy and radiation given at the same time to treat cancer.
PamiparibDrug
Also called BGB-290
An anti-cancer drug that targets specific cells to help fight cancer given by IV (through a needle inserted into a vein).
HydroxyureaDrug
Also called Hydrea, Droxia
A chemotherapy drug given in pill form; used to treat leukemia and head and neck cancer.
Fluorouracil (5FU)Drug
Also called Tolak, Fluoroplex, Efudex
A chemotherapy drug used to treat different types of cancer.
TislelizumabDrug
Also called BGB-A317
An anti-cancer drug.
| Study group | Role | What they receive |
|---|---|---|
| Dose-Finding Group 1: Dose Level 1 (Part 1 of Study) | Experimental | The 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. Receives: Radiation: Chemoradiation; Drug: Pamiparib; Drug: Hydroxyurea; Drug: Fluorouracil (5FU); Drug: Tislelizumab |
| Dose-Finding Group 2: Dose Level 2 (Part 1 of Study) | Experimental | The 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. Receives: Radiation: Chemoradiation; Drug: Pamiparib; Drug: Hydroxyurea; Drug: Fluorouracil (5FU); Drug: Tislelizumab |
| Dose-Finding Group 3: Dose Level 3 (Part 1 of Study) | Experimental | The 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. Receives: Radiation: Chemoradiation; Drug: Pamiparib; Drug: Hydroxyurea; Drug: Fluorouracil (5FU); Drug: Tislelizumab |
| Dose Expansion Group ( Part II of Study) | Experimental | Part 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. Receives: Radiation: Chemoradiation; Drug: Pamiparib; Drug: Hydroxyurea; Drug: Fluorouracil (5FU); Drug: Tislelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 15 months
Secondary outcomes (2)
Progression Free Survival of Participants Receiving Pamiparib in Combination with 5 Fluorouracil-Hydroxea (FHX) and Tislelizumab
The progression free survival (PFS) of participants receiving pamiparib in combination with FHX and tislelizumab in subjects with recurrent head and neck squamous cell carcinoma, defined as the time from initiation of treatment with tislelizumab to the earliest of disease progression per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause.
Measured: 15 months
Overall Free Survival of Participants Receiving Pamiparib in Combination with 5 Fluorouracil-Hydroxea (FHX) and Tislelizumab
Overall survival (OS) of participants receiving pamiparib in combination with FHX and tislelizumab in subjects with recurrent head and neck squamous cell carcinoma, defined as the time from initiation of treatment with tislelizumab to death due to any cause.
Measured: 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2022
- Study start7 Mar 2023
- Primary completion1 Jan 2028 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ari Rosenberg, MD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05526924
- Sponsor's protocol ID
- IRB22-0578
- Status last verified
- Mar 2026
- First submitted
- 31 Aug 2022
- Last updated
- 4 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05526924
- Acronym / sponsor ID
- IRB22-0578
- Conditions
- Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma, Head and Neck Carcinoma, Head and Neck Cancer Stage IV, Head and Neck Cancers - Throat
- Keywords
- head and neck cancer, head and neck carcinoma, Head and Neck Squamous Cell Carcinoma, throat cancer, HNSCC treatment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- 7 Mar 2023 (actual)
- Primary completion
- 1 Jan 2028 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 2 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
During the study, participants will first receive one dose of tislelziumab. Tislelzumab is an experimental drug, meaning, it is not approved by the U.S. Food and Drug Administration (FDA) to treat cancer. Next, participants will receive pamiparib in combination with CRT (chemotherapy and radiation). Pamiparib is also an experimental drug and not approved by the FDA.
Chemoradiotherapy will consist of chemotherapy drugs, 5-FU and hydroxyurea, plus radiation therapy. 5-FU is approved by the FDA to treat many types of cancer such as colon cancer but has not been approved for the treatment of head and neck cancer. Its use is experimental in this study. Hydroxyurea is approved by the FDA to treat many types of cancer, including in combination with radiation therapy for the local control of squamous carcinoma of the head and neck. The combination of tislelizumab, hydroxyurea with 5-FU, radiation, and pamiparib, is considered experimental in this study.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose-Finding Group 1: Dose Level 1 (Part 1 of Study) | Experimental | Radiation: Chemoradiation, Drug: Pamiparib, Drug: Hydroxyurea, Drug: Fluorouracil (5FU), Drug: TislelizumabThe 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) | Experimental | Radiation: Chemoradiation, Drug: Pamiparib, Drug: Hydroxyurea, Drug: Fluorouracil (5FU), Drug: TislelizumabThe 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) | Experimental | Radiation: Chemoradiation, Drug: Pamiparib, Drug: Hydroxyurea, Drug: Fluorouracil (5FU), Drug: TislelizumabThe 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) | Experimental | Radiation: Chemoradiation, Drug: Pamiparib, Drug: Hydroxyurea, Drug: Fluorouracil (5FU), Drug: TislelizumabPart 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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.
Key exclusion criteria (25 listed)
- • Previously untreated patients with locoregional-only disease are not eligible.
- 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)
- o Note: Vaccines for COVID-19 are allowed except for any live vaccine that may be developed. Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed within 28 days prior to initiation of treatment. Vaccines should not be given during the chemo-radiation phase until marrow function has normalized as vaccines may not be efficacious during periods of marrow suppression.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ChemoradiationA combination of chemotherapy and radiation given at the same time to treat cancer. | Radiation | Dose Expansion Group ( Part II of Study), Dose-Finding Group 1: Dose Level 1 (Part 1 of Study), Dose-Finding Group 2: Dose Level 2 (Part 1 of Study), Dose-Finding Group 3: Dose Level 3 (Part 1 of Study) |
| PamiparibAlso: BGB-290An anti-cancer drug that targets specific cells to help fight cancer given by IV (through a needle inserted into a vein). | Drug | Dose Expansion Group ( Part II of Study), Dose-Finding Group 1: Dose Level 1 (Part 1 of Study), Dose-Finding Group 2: Dose Level 2 (Part 1 of Study), Dose-Finding Group 3: Dose Level 3 (Part 1 of Study) |
| HydroxyureaAlso: Hydrea, DroxiaA chemotherapy drug given in pill form; used to treat leukemia and head and neck cancer. | Drug | Dose Expansion Group ( Part II of Study), Dose-Finding Group 1: Dose Level 1 (Part 1 of Study), Dose-Finding Group 2: Dose Level 2 (Part 1 of Study), Dose-Finding Group 3: Dose Level 3 (Part 1 of Study) |
| Fluorouracil (5FU)Also: Tolak, Fluoroplex, EfudexA chemotherapy drug used to treat different types of cancer. | Drug | Dose Expansion Group ( Part II of Study), Dose-Finding Group 1: Dose Level 1 (Part 1 of Study), Dose-Finding Group 2: Dose Level 2 (Part 1 of Study), Dose-Finding Group 3: Dose Level 3 (Part 1 of Study) |
| TislelizumabAlso: BGB-A317An anti-cancer drug. | Drug | Dose Expansion Group ( Part II of Study), Dose-Finding Group 1: Dose Level 1 (Part 1 of Study), Dose-Finding Group 2: Dose Level 2 (Part 1 of Study), Dose-Finding Group 3: Dose Level 3 (Part 1 of Study) |
Primary outcome
Maximum Tolerated Dose/Recommended Phase 2 Dose of Pamiparib in Combination with 5 Fluorouracil-Hydroxea (FHX) and Tislelizumab
Time frame: 15 months
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.
2 secondary outcomes
Progression Free Survival of Participants Receiving Pamiparib in Combination with 5 Fluorouracil-Hydroxea (FHX) and Tislelizumab
Time frame: 15 months
Overall Free Survival of Participants Receiving Pamiparib in Combination with 5 Fluorouracil-Hydroxea (FHX) and Tislelizumab
Time frame: 15 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2026.
- Individual participant dataSharing planned: Yes
Related trials for Head and Neck Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
Proton Re-irradiation in Patients With Recurrent or Second Primary Head and Neck Cancer , a Multicentre Phase II Single Arm Trial
Head & Neck Cancer
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 4
Lidocaine Infiltration and Neuroimmunomodulation in Head and Neck Cancer Surgery
Head and Neck Cancer (H&N)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ari Rosenberg, MD principal investigator
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Chemoradiation, Pamiparib and Hydroxyurea in people with Head and Neck Cancer and Head and Neck Squamous Cell Carcinoma, run by University of Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cancer Trial Intake (1-855-702-8222, cancerclinicaltrials@bsd.uchicago.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose/Recommended Phase 2 Dose of Pamiparib in Combination with 5 Fluorouracil-Hydroxea (FHX) and Tislelizumab (time frame: 15 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2026.