Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This phase I trial studies the side effects and best dose of birinapant when given together
with intensity modulated re-irradiation therapy (IMRRT) in treating patients with head and
neck squamous cell carcinoma that has come back at or near the same place as the original
(primary) tumor (locally recurrent). Birinapant may stop the growth of tumor cells by
blocking IAP, a protein needed for tumor cell survival. IMRRT uses thin beams of radiation of
different intensities that are aimed at the tumor from many angles. This type of
re-irradiation therapy reduces the damage to healthy tissue near the tumor. Giving birinapant
with IMRRT may lower the chance of head and neck squamous cell carcinoma growing or
spreading.
Phase
Phase 1
Funding Agency/Sponsor
National Cooperative Group
Disease
Head and Neck Cancer
Enrollment Eligibility
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed locally recurrent HNSCC,
including nasopharyngeal or sinonasal cancer for whom re-irradiation for local control
is considered standard of care
- Patients with human papillomavirus (HPV)-negative or HPV-positive head and neck cancer
are eligible
- Patients who have had prior treatment with immune therapies are eligible
- Patients must have received curative-intent platinum- and/or cetuximab-based
chemoradiotherapy or radiotherapy alone
- Patients must have completed their last treatment dose with chemotherapy or
immunotherapy at least 4 weeks (6 weeks for nitrosoureas or mitomycin C) before
enrolling on study
- Patients must have completed their last treatment dose with radiotherapy at least 6
months before enrolling on study
- Patients who have had major surgery must be fully recovered and require a recovery
period of at least 4 weeks prior to enrolling on study
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Hemoglobin >= 9 g/dL (transfusion permitted)
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin within 1.5 x the upper limit of normal (ULN) institutional limits
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional upper limit of normal
- Serum creatinine =< 1.5 x upper limit of normal (ULN), OR: Creatinine clearance >= 50
mL/min according to Cockcroft Gault formula or other institutional methods
- Patients must have a corrected QT interval by Fridericia (QTcF) =< 480 msec
- International normalized ratio (INR) =< 1.5 and no clinically significant bleeding
event within the past six months
- Ability to understand and the willingness to sign a written informed consent document
- Patients must have measurable disease, per Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1
- The effects of birinapant on the developing human fetus are unknown. For this reason,
women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) beginning at study entry and
for the duration of study participation. Male study participants should use an
additional barrier method of contraception for 30 days following the last dose of
birinapant. 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
Exclusion Criteria:
- Eligibility for curative-intent surgery, unless the patient is considered a poor
surgical candidate related to resectability, functional outcome, or prefers
non-surgical therapy
- More than 2 lines of palliative systemic therapy (platinum-, taxane- or
cetuximab-based chemotherapy or immunotherapy)
- Patients who are receiving any other investigational agents
- 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
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to birinapant
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
- Pregnant women are excluded from this study because birinapant may have 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
birinapant, breastfeeding should be discontinued prior to enrollment. A negative
pregnancy test is required for women of childbearing potential. Women who are
postmenopausal (age-related amenorrhea >= 12 consecutive months, or who had undergone
hysterectomy or bilateral oophorectomy are exempt from pregnancy testing. If
necessary, to confirm postmenopausal status, a follicle stimulating hormone (FSH)
level may be included at screening
- Human immunodeficiency virus (HIV) positive patients on combination antiretroviral
therapy are ineligible because of the potential for pharmacokinetic interactions with
birinapant
- Patients requiring the use of anti-tumor necrosis factor (anti TNF) therapies, such as
infliximab, or patients who have received treatment with anti-TNF therapies within 5
half-lives of the drug (48 days for infliximab, 55 days for golimumab, 70 days for
certolizumab and adalimumab, and 16 days for etanercept)
- Patients with previous exposure to birinapant