Testing the Addition of a New Anti-Cancer Drug, Triapine, to the Usual Chemotherapy Treatment (Cisplatin) During Radiation Therapy for Advanced-stage Cervical and Vaginal Cancers
Purpose
This randomized phase III trial studies radiation therapy and cisplatin with triapine to see how well they work compared to the standard radiation therapy and cisplatin alone in treating patients with newly diagnosed stage IB2, II, or IIIB-IVA cervical cancer or stage II-IVA vaginal cancer. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, 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. Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether radiation therapy and cisplatin are more effective with triapine in treating cervical or vaginal cancer.
Conditions
- Cervical Adenocarcinoma
- Cervical Adenosquamous Carcinoma
- Cervical Squamous Cell Carcinoma, Not Otherwise Specified
- Stage IB2 Cervical Cancer AJCC v6 and v7
- Stage II Cervical Cancer AJCC v7
- Stage II Vaginal Cancer AJCC v6 and v7
- Stage IIA Cervical Cancer AJCC v7
- Stage IIB Cervical Cancer AJCC v6 and v7
- Stage III Vaginal Cancer AJCC v6 and v7
- Stage IIIB Cervical Cancer AJCC v6 and v7
- Stage IVA Cervical Cancer AJCC v6 and v7
- Stage IVA Vaginal Cancer AJCC v6 and v7
- Vaginal Adenocarcinoma
- Vaginal Adenosquamous Carcinoma
- Vaginal Squamous Cell Carcinoma, Not Otherwise Specified
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Patient has a new, unrated histologic diagnosis of stage IB2 (> 4 cm), II, IIIB or IVA squamous, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix or stage II-IVA squamous, adenocarcinoma, or adenosquamous carcinoma of the vagina not amenable to curative surgical resection alone; the presence or absence of para-aortic lymph node metastasis will be based on pre-therapy 18F-FDG PET/CT; NOTE: if the baseline 18F-FDG PET/CT identifies hypermetabolic para-aortic disease, such patients will NOT be eligible; the patient must be able to tolerate imaging requirements of an 18F-FDG PET/CT scan - Patient must provide study specific informed consent prior to study entry - Patient must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2 or equivalent - Absolute neutrophil count > 1,500/uL - Platelets > 100,000/uL - Hemoglobin > 10 g/dL - Total bilirubin < 2.0 mg/dL - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 X institutional upper limit of normal - Prothrombin time (PT)/activated partial thromboplastin time (aPTT) < 1.5 X institutional upper limit of normal - Creatinine =< 1.5 mg/dL to receive weekly cisplatin - Patients whose serum creatinine is between 1.5 and 1.9 mg/dL are eligible for cisplatin if the estimated creatinine clearance (CCr) is >= 30 ml/min; for the purpose of estimating the CCr, the formula of Cockcroft and Gault for females should be used - Patient does not have uncontrolled diabetes mellitus (i.e., fasting blood glucose > 200 mg/dL) - Patient has a life expectancy of greater than 20 weeks - Patient does not have known brain metastases (testing optional) - Patient does not have known human immunodeficiency virus syndrome (HIV, testing optional); known HIV-positive patients receiving combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with triapine - Patient does not have a known allergy to compounds of similar or biologic composition as triapine - Patient does not have known glucose-6-phosphate dehydrogenase (G6PD) deficiency as the condition interferes with triapine antidote metabolism (G6PD testing optional) - Patient is not actively breastfeeding (or has agreed to discontinue breastfeeding before the initiation of protocol therapy)
Exclusion Criteria
- Patient has another concurrent active invasive malignancy - Patient has had a prior invasive malignancy diagnosed within the last three years (except [1] non-melanoma skin cancer or [2] prior in situ carcinoma of the cervix); patients are excluded if they have received prior pelvic radiotherapy for any reason that would contribute radiation dose that would exceed tolerance of normal tissues at the discretion of the treating physician - Patient has uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within six months of protocol initiation, cardiac arrhythmia within six months of protocol initiation; known inadequately controlled hypertension; clinically significant pulmonary disease including dyspnea at rest, or patients requiring supplemental oxygen, or poor pulmonary reserve; or clinically significant renal function impairment (baseline serum creatinine > 2 mg/dL); or psychiatric illness/social situations that would limit compliance with study requirements - Patient is receiving another investigational agent for the treatment of cancer - Patient is currently pregnant - Patient does not agree to use two forms of birth control if they are of child-bearing potential - Patients who have had a hysterectomy or are planning to have an adjuvant hysterectomy following radiation as part of their cervical cancer treatment are ineligible - Patients scheduled to be treated with adjuvant consolidation chemotherapy or other anti-neoplastic therapy at the conclusion of their standard chemoradiation - Patients with self-reported or known diagnosis of G6PD deficiency - Patients with vaginal cancer may have previously undergone a hysterectomy for various indications; patients with vaginal cancer who underwent a hysterectomy for treatment of cervical cancer less than five years prior to their diagnosis of vaginal cancer are ineligible
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Arm I (cisplatin, IMRT or RT, brachytherapy) |
Patients receive cisplatin IV over 90 minutes on days 2, 9, 16, 23, 30, (and day 36 or 37 at the treating physician's discretion). Patients then undergo EBRT (either conventional RT or IMRT) QD 5 days a week for 25 fractions followed by LDR or HDR brachytherapy according to institution's standards. Treatment continues in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Arm II (cisplatin, IMRT or RT, brachytherapy, triapine) |
Patients receive cisplatin and undergo EBRT followed by brachytherapy as in Arm I. Patients also receive triapine IV over 2 hours on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33. Treatment continues in the absence of disease progression or unacceptable toxicity. |
|
Recruiting Locations
Birmingham, Alabama 35233
Anchorage, Alaska 99508
Tucson, Arizona 85719
Little Rock, Arkansas 72205
Site Public Contact
501-686-8274
La Jolla, California 92093
Hartford, Connecticut 06102
Site Public Contact
860-545-5363
Tampa, Florida 33612
Savannah, Georgia 31405
Boise, Idaho 83712
Fruitland, Idaho 83619
Meridian, Idaho 83642
Nampa, Idaho 83686
Chicago, Illinois 60611
Chicago, Illinois 60612
Site Public Contact
312-864-5204
Indianapolis, Indiana 46260
New Orleans, Louisiana 70112
New Orleans, Louisiana 70121
Bethesda, Maryland 20889-5600
Site Public Contact
301-319-2100
Detroit, Michigan 48201
Farmington Hills, Michigan 48334
Minneapolis, Minnesota 55455
Site Public Contact
612-624-2620
Jackson, Mississippi 39216
Site Public Contact
601-815-6700
Las Vegas, Nevada 89169
Camden, New Jersey 08103
Site Public Contact
856-325-6757
Albuquerque, New Mexico 87102
Buffalo, New York 14263
Rochester, New York 14620
Site Public Contact
585-341-8113
Rochester, New York 14642
Site Public Contact
585-275-5830
Syracuse, New York 13210
Site Public Contact
315-464-5476
Beachwood, Ohio 44122
Chardon, Ohio 44024
Cincinnati, Ohio 45219
Cleveland, Ohio 44106
Cleveland, Ohio 44109
Cleveland, Ohio 44111
Cleveland, Ohio 44195
Mentor, Ohio 44060
West Chester, Ohio 45069
Westlake, Ohio 44145
Westlake, Ohio 44145
Oklahoma City, Oklahoma 73104
Dallas, Texas 75235
Dallas, Texas 75390
Houston, Texas 77030
Site Public Contact
713-790-2700
Houston, Texas 77030
Site Public Contact
713-792-3245
Sugar Land, Texas 77479
Site Public Contact
281-242-2873
Seattle, Washington 98122-4307
Morgantown, West Virginia 26506
San Juan, Puerto Rico 00927
San Juan, Puerto Rico 00936
Site Public Contact
787-763-1296
More Details
- NCT ID
- NCT02466971
- Status
- Recruiting
- Sponsor
- National Cancer Institute (NCI)
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate the efficacy of the experimental regimen of triapine (3AP), cisplatin, and radiation to increase overall survival relative to the standard/control regimen of cisplatin and radiation in women with uterine cervix or vaginal cancer. SECONDARY OBJECTIVE: I. To determine the relative progression-free survival impact of triapine-cisplatin radio-chemotherapy and cisplatin radio-chemotherapy. TERTIARY OBJECTIVES: I. To evaluate incidence and severity of hematologic and gastrointestinal (GI) adverse events by radiation modality; image guided intensity modulated radiation therapy (IG-IMRT) versus conventional pelvic radiotherapy. II. To summarize and compare differences in acute adverse events (Common Terminology Criteria for Adverse Events [CTCAE], version [v]4.0) by treatment arm and by radiation modality. III. To summarize and compare differences in chronic or late (>= 30-days from off study treatment date) adverse events (CTCAE, v4.0) by treatment arm and by radiation modality. IV. To determine peripheral blood methemoglobin proportion before and after triapine infusion (optional for Arm 2 patients). V. To explore whether knowledge-based planning (KBP) can improve IG-IMRT plans compared to plans that would have been delivered without KBP, estimate the resulting toxicity reduction using normal tissue complication probability (NTCP) models, and determine whether KBP should be a requirement for future IG-IMRT protocols. VI. To determine the post-therapy 3-month fludeoxyglucose F-18 (18F-FDG) PET/CT metabolic complete response rate by treatment arm VII. To compare acute toxicity and chemotherapy delivery for atlas-based IG-IMRT vs. positron emission tomography (PET)/computed tomography (CT)-based IG-IMRT vs. conventional radiation therapy (RT), and assess the impact of treatment on changes in hematopoietic compensatory response. VIII. To develop and validate machine learning and radiomics techniques for dose accumulation, automated treatment planning, and prediction of treatment response. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive cisplatin intravenously (IV) over 90 minutes on days 2, 9, 16, 23, 30, (and day 36 or 37 at the treating physician's discretion). Patients then undergo external beam radiation therapy (EBRT) (either conventional RT or intensity modulated radiation therapy [IMRT]) once daily (QD) 5 days a week for 25 fractions followed by low dose rate (LDR) or high dose rate (HDR) brachytherapy according to institution's standards. Treatment continues in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive cisplatin and undergo EBRT followed by brachytherapy as in Arm I. Patients also receive triapine IV over 2 hours on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 1 and 3 months, every 3 months for 2 years, and then every 6 months for 3 years. The patient data from NCI #9434 will be merged with NRG-GY006 per the Protocol Analysis Plan.