This study is NOT currently recruiting participants.
Number
19-C-0041
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Completed Study; data analyses ongoing Gender: Male & Female Min Age: 18 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Neonates;Pregnant Women;Children
Keywords
Second Mitochondrial Activator of Caspases (SMAC); Radiation Therapy; human papillomavirus (HPV); Cetuximab; Relapsed Head and Neck Cancer
Recruitment Keyword(s)
None
Condition(s)
Head Cancer; Facial Cancer; Neck Cancer; upper aerodigestive tract cancer; Oral Cancer
Investigational Drug(s)
Birinapant
Investigational Device(s)
Intervention(s)
Drug: Birinapant Radiation: Intensity modulated re-irradiation therapy (IMMRT)
Supporting Site
National Cancer Institute
Head and neck cancer is a group of cancers that start in the mouth, nose, throat, larynx and sinuses. The usual treatment is surgery, radiation, chemotherapy, or a combination of those. Approximately 50% of HPV-negative head and neck cancer patients that have been treated with any of these modalities will have a recurrence. For these patients, current treatment options include surgery and re-irradiation with chemotherapy, which can reduce symptoms and may stop the tumor from growing but in the majority of cases, only for a few months. In this trial, researchers want to see if they can cure or significantly lower the chance of head and neck cancer growing back or spreading by adding the new agent birinapant to re-irradiation.
Objective:
To test the safety of birinapant and re-irradiation at different doses in patients with head and neck cancer.
Eligibility:
Adults age 18 and older with head and neck cancer who are candidates for re-irradiation.
Design:
Participants will be screened with a review of their medical record. Participants will have exams and procedures that are part of their usual care. Participants will also have a test of heart activity before treatment.
Participants will have urine pregnancy tests, if female.
Participants will have blood and tumor samples taken 2 times and stored for research. The study lasts 6 weeks.
Participants will get radiation for 5 days a week (Monday Friday) for all 6 weeks.
Participant will get the study drug on 4 Tuesdays. They will get it in an arm vein over 30 minutes each time.
About 4 weeks after the study ends, participants will have a follow-up visit. They will have a physical exam, health questions, and blood tests.
Participants may have scans 4 times over the next 2 years. Participants will get an email or phone call every 6 months.
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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 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 greater than or equal to 18 years. -ECOG performance status less than or equal to 2. -Patients must have normal organ and marrow function as defined below: --Hemoglobin greater than or equal to 10 g/dL (transfusion permitted) --Absolute neutrophil count greater than or equal to 1,500/mcL --Platelets greater than or equal to 75,000/mcL --Total bilirubin within 1.5 x the upper limit of normal (ULN) institutional limits --AST(SGOT)/ALT(SGPT) less than or equal to 2.5 (SqrRoot) institutional upper limit of normal --Serum creatinine <=1.5x upper limit of normal (ULN), OR: --Creatinine clearance >= 50 mL/min according to Cockcroft Gault formula or other institutional methods. -Cardiac function - Patients must have a QTcF less than or equal to 480 msec. -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. - 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 cetuximabbased 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. -Pregnancy or lactation period. 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 greater than or equal to 12 consecutive months, or who had undergone hysterectomy or bilateral oophorectomy are exempt from pregnancy testing. If necessary, to confirm postmenopausal status, a FSH level may be included at screening. - 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, and16 days for etanercept). - Patients with previous exposure to birinapant.
-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 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 greater than or equal to 18 years.
-ECOG performance status less than or equal to 2.
-Patients must have normal organ and marrow function as defined below:
--Hemoglobin greater than or equal to 10 g/dL (transfusion permitted)
--Absolute neutrophil count greater than or equal to 1,500/mcL
--Platelets greater than or equal to 75,000/mcL
--Total bilirubin within 1.5 x the upper limit of normal (ULN) institutional limits
--AST(SGOT)/ALT(SGPT) less than or equal to 2.5 (SqrRoot) institutional upper limit of normal
--Serum creatinine <=1.5x upper limit of normal (ULN), OR:
--Creatinine clearance >= 50 mL/min according to Cockcroft Gault formula or other institutional methods.
-Cardiac function - Patients must have a QTcF less than or equal to 480 msec.
-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.
- 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 cetuximabbased 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.
-Pregnancy or lactation period. 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 greater than or equal to 12 consecutive months, or who had undergone hysterectomy or bilateral oophorectomy are exempt from pregnancy testing. If necessary, to confirm postmenopausal status, a FSH level may be included at screening.
- 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, and16 days for etanercept).
- Patients with previous exposure to birinapant.
Principal Investigator
Referral Contact
For more information: