Birinapant and Intensity Modulated Re-Irradiation Therapy in Treating Patients With Locally Recurrent Head and Neck Squamous Cell Carcinoma

  • STATUS
    Recruiting
  • End date
    Jul 31, 2022
  • participants needed
    34
  • sponsor
    National Cancer Institute (NCI)
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Updated on 1 April 2021
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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). Drugs used in chemotherapy, such as birinapant, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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.

Description

PRIMARY OBJECTIVE:

I. Determine the toxicities and maximum tolerated dose (MTD) of birinapant concurrent with intensity modulated re-irradiation therapy (IMRRT).

SECONDARY OBJECTIVES:

I. Determine the objective response rate of patients with locoregionally recurrent head and neck squamous cell carcinoma (HNSCC) treated with re-irradiation and birinapant.

II. Determine the local-regional control, progression free survival (PFS), and overall survival.

III. Determine if FADD and/or BIRC2/3 copy gain in tumor tissue or in the blood are associated with improved response, locoregional control (LCR), progression-free survival and overall survival.

IV. Determine the feasibility of detecting effects of birinapant and re-irradiation on pilot pharmacodynamic markers in tumor tissue, by using microwestern to assess decrease in drug targets IAP1/2 and increase in apoptosis/necroptosis markers caspase 3 and mixed lineage kinase domain like pseudokinase gene (MLKL).

EXPLORATORY OBJECTIVES:

I. Explore if mutational load detected with whole exome and ribonucleic acid (RNA)-sequencing of tumor tissue influences objective response rate.

II. Explore if PD-L1, CD8 T-cell tumor infiltration, TNFalpha, and other immune related biomarkers in tumor tissue are associated with objective response rate.

III. Explore the pharmacokinetics of birinapant in combination with radiotherapy in blood samples.

IV. Explore whether specific germline single-nucleotide polymorphisms (SNPs) are associated with response to birinapant and reirradiation.

OUTLINE: This is a dose-escalation study of birinapant.

Beginning on day 1, patients undergo IMRRT 5 days a week (Monday-Friday). Patients also receive birinapant intravenously (IV) over 30 minutes on days 2 and 9 of each cycle. Treatment repeats every 3 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 28 days, and at 3, 6, 9, 12, 18, and 24 months until confirmation of disease progression.

Details
Condition Recurrent Head and Neck Squamous Cell Carcinoma, Locally Recurrent Head and Neck Squamous Cell Carcinoma
Treatment intensity-modulated radiation therapy, Birinapant
Clinical Study IdentifierNCT03803774
SponsorNational Cancer Institute (NCI)
Last Modified on1 April 2021

Eligibility

 Yes No Not Sure

Inclusion Criteria

Do you have any of these conditions: Do you have Recurrent Head and Neck Squamous Cell Carcinoma??
Do you have any of these conditions: Locally Recurrent Head and Neck Squamous Cell Carcinoma or Recurrent Head and Neck Squamous Cell Carcinoma?
Do you have any of these conditions: Locally Recurrent Head and Neck Squamous Cell Carcinoma or Recurrent Head and Neck Squamous Cell Carcinoma?
Do you have any of these conditions: Locally Recurrent Head and Neck Squamous Cell Carcinoma or Recurrent Head and Neck Squamous Cell Carcinoma?
Do you have any of these conditions: Recurrent Head and Neck Squamous Cell Carcinoma or Locally Recurrent Head and Neck Squamous Cell Carcinoma?
Do you have any of these conditions: Locally Recurrent Head and Neck Squamous Cell Carcinoma or Recurrent Head and Neck Squamous Cell Carcinoma?
Do you have any of these conditions: Recurrent Head and Neck Squamous Cell Carcinoma or Locally Recurrent Head and Neck Squamous Cell Carcinoma?
Do you have any of these conditions: Do you have Recurrent Head and Neck Squamous Cell Carcinoma??
Do you have any of these conditions: Do you have Recurrent Head and Neck Squamous Cell Carcinoma??
Is your age greater than or equal to 18 yrs?
Do you have any of these conditions: Do you have Recurrent Head and Neck Squamous Cell Carcinoma??
Do you have any of these conditions: Do you have Recurrent Head and Neck Squamous Cell Carcinoma??
Do you have any of these conditions: Do you have Recurrent Head and Neck Squamous Cell Carcinoma??
Do you have any of these conditions: Do you have Recurrent Head and Neck Squamous Cell Carcinoma??
Do you have any of these conditions: Do you have Recurrent Head and Neck Squamous Cell Carcinoma??
Do you have Recurrent Head and Neck Squamous Cell Carcinoma?
Gender: Male or Female
Patients must have histologically or cytologically confirmed locally recurrent HNSCC 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
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
Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal. Creatinine clearance will be determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
Patients must have a corrected QT interval by Fredericia (QTcF) =< 480 msec
International normalized ratio (INR)/prothrombin time (PT)/partial thromboplastin time (PTT) =<1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants; =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
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
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
Participants with nasopharyngeal carcinoma are excluded
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
Human immunodeficiency virus (HIV) positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with birinapant
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
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
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