Trial Title:
Dosing Study of Radiation Combined With Tislelizumab and Pamiparib in Patients With Previously Treated Head and Neck Cancer
NCT ID:
NCT05526924
Condition:
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
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Fluorouracil
Tislelizumab
Hydroxyurea
Pamiparib
Conditions: Keywords:
head and neck cancer
head and neck carcinoma
Head and Neck Squamous Cell Carcinoma
throat cancer
HNSCC treatment
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Chemoradiation
Description:
A combination of chemotherapy and radiation given at the same time to treat cancer.
Arm group label:
Dose Expansion Group ( Part II of Study)
Arm group label:
Dose-Finding Group 1: Dose Level 1 (Part 1 of Study)
Arm group label:
Dose-Finding Group 2: Dose Level 2 (Part 1 of Study)
Arm group label:
Dose-Finding Group 3: Dose Level 3 (Part 1 of Study)
Intervention type:
Drug
Intervention name:
Pamiparib
Description:
An anti-cancer drug that targets specific cells to help fight cancer given by IV (through
a needle inserted into a vein).
Arm group label:
Dose Expansion Group ( Part II of Study)
Arm group label:
Dose-Finding Group 1: Dose Level 1 (Part 1 of Study)
Arm group label:
Dose-Finding Group 2: Dose Level 2 (Part 1 of Study)
Arm group label:
Dose-Finding Group 3: Dose Level 3 (Part 1 of Study)
Other name:
BGB-290
Intervention type:
Drug
Intervention name:
Hydroxyurea
Description:
A chemotherapy drug given in pill form; used to treat leukemia and head and neck cancer.
Arm group label:
Dose Expansion Group ( Part II of Study)
Arm group label:
Dose-Finding Group 1: Dose Level 1 (Part 1 of Study)
Arm group label:
Dose-Finding Group 2: Dose Level 2 (Part 1 of Study)
Arm group label:
Dose-Finding Group 3: Dose Level 3 (Part 1 of Study)
Other name:
Hydrea
Other name:
Droxia
Intervention type:
Drug
Intervention name:
Fluorouracil (5FU)
Description:
A chemotherapy drug used to treat different types of cancer.
Arm group label:
Dose Expansion Group ( Part II of Study)
Arm group label:
Dose-Finding Group 1: Dose Level 1 (Part 1 of Study)
Arm group label:
Dose-Finding Group 2: Dose Level 2 (Part 1 of Study)
Arm group label:
Dose-Finding Group 3: Dose Level 3 (Part 1 of Study)
Other name:
Tolak
Other name:
Fluoroplex
Other name:
Efudex
Intervention type:
Drug
Intervention name:
Tislelizumab
Description:
An anti-cancer drug.
Arm group label:
Dose Expansion Group ( Part II of Study)
Arm group label:
Dose-Finding Group 1: Dose Level 1 (Part 1 of Study)
Arm group label:
Dose-Finding Group 2: Dose Level 2 (Part 1 of Study)
Arm group label:
Dose-Finding Group 3: Dose Level 3 (Part 1 of Study)
Other name:
BGB-A317
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.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
- 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:
1. 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.
2. Women must not be breastfeeding.
3. 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).
4. 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).
5. 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.
Exclusion Criteria:
- • 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).
- 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).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The University of Chicago
Address:
City:
Chicago
Zip:
60637
Country:
United States
Status:
Recruiting
Contact:
Last name:
Cancer Clinical Trials Office
Phone:
855-702-8222
Email:
cancerclinicaltrials@bsd.uchicago.edu
Start date:
March 7, 2023
Completion date:
January 1, 2026
Lead sponsor:
Agency:
University of Chicago
Agency class:
Other
Source:
University of Chicago
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05526924
