Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Uterine Cervical Neoplasms

Carcinoma

Adenocarcinoma

Carcinoma, Squamous Cell

Vaginal Neoplasms

Carcinoma, Adenosquamous

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Vaginal Diseases

Vaginal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

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.

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.

Brachytherapy

External Beam Radiation Therapy

Intensity-Modulated Radiation Therapy

Laboratory Biomarker Analysis

Radiation Therapy

Triapine

Charles A Leath

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.

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. (05/30/2017) 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. (05/30/2017) 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. (05/30/2017) 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.

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

A Randomized Phase III Trial of Radiation Therapy and Cisplatin Alone or in Combination With Intravenous Triapine in Women With Newly Diagnosed Bulky Stage IB2, Stage II, IIIB, or IVA Cancer of the Uterine Cervix or Stage II-IVA Vaginal Cancer

Number of participants with hematologic toxicity during treatment period, where hematologic toxicity is defined as occurrence of any grade 3 or higher adverse events for neutropenia, leukopenia, lymphopenia, anemia, or thrombocytopenia. Adverse events are graded and categorized using CTCAE v4.0.

Number of participants with a maximum grade of 3 or higher that occurred during follow-up period. Adverse events are graded and categorized using CTCAE v4.0.

Peripheral blood methemoglobin collected at baseline and 1, 3, 5 and 24 hours after Triapine infusion on Day 1 in Arm II.

The assessment of metabolic complete response is based on the ratio of post 3-month therapy PET/CT maximum standardized update value (SUV) to pre-therapy PET/CT maximum SUV. The metabolic complete response is classified as complete response for a ratio of 0.33 or less, or partial response for a ratio between 0.34 and 0.75, or stable response for a ratio greater that 0.75 but less than 1.25, or progressive response for a ratio greater than 1.25.

Estimate for probability of overall survival at 3 years by Kaplan-Meier method, where overall survival is defined as the time from randomization to time of death due to any cause or the date of last contact, whichever occurs first.

Estimate for probability of progression free at 3 years by Kaplan-Meier method, where progression-free survival is defined as the time from randomization to the date of first documented disease recurrence/progression, death from any cause or date of last contact, whichever occurs first. Recurrence is defined as clinical, radiological or histological evidence of recurrent disease post study treatment. Disease progression will be determined from the physical examinations, which were conducted during treatment (day 9, 16, 23, 30 and 37) and follow-up (1 and 3 months after completing protocol therapy, every 3 months for years 1 and 2, and every 6 months for years 3, 4 and 5), and the PET/CT scan conducted 3 months after the end of treatment. Please note that progression defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1) is not required by the protocol.

Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.

NRG Oncology

National Cancer Institute (NCI)

All Adverse Events (AEs) occurring during treatment and up to 30 days after stopping the study treatment for participants who received any study treatment. Note that the population is different for all-cause mortality and adverse events. For all-cause mortality the population is "all eligible participants." For adverse event reporting, the population is "all patients who received any study treatment."

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.

Brachytherapy: Undergo brachytherapy

Cisplatin: Given IV

External Beam Radiation Therapy: Undergo EBRT

Intensity-Modulated Radiation Therapy: Undergo IMRT

Laboratory Biomarker Analysis: Correlative studies

Radiation Therapy: Undergo conventional RT

Arm I (Cisplatin, IMRT or RT, Brachytherapy)

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.

Brachytherapy: Undergo brachytherapy

Cisplatin: Given IV

Intensity-Modulated Radiation Therapy: Undergo IMRT

Laboratory Biomarker Analysis: Correlative studies

Radiation Therapy: Undergo conventional RT

Triapine: Given IV

Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine)

Total

Age, Continuous

20-29 years

30-39 years

40-49 years

50-59 years

60-69 years

70-79 years

>= 80 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Christopher Purdy on behalf of Wei Deng, PhD

Overall Survival (OS) Rate at 3 Years

Progression-free Survival (PFS) Rate at 3 Years

Anemia

Other blood and lymphatic system disorders

White blood cell count decreased

Platelet count decreased

Neutrophil count decreased

Other investigations

Cardiac disorders

Eye disorders

Gastrointestinal disorders

General disorders

Hepatobiliary disorders

Infections and infestations

Metabolism and nutrition disorders

Musculoskeletal and connective tissue disorders

Neoplasms benign, malignant and unspecified

Nervous system disorders

Psychiatric disorders

Renal and urinary disorders

Reproductive system and breast disorders

Respiratory, thoracic and mediastinal disorders

Skin and subcutaneous tissue disorders

Surgical and medical procedures

Vascular disorders

Participants who received any study treatment

Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period

Number of Participants With Hematologic Toxicity During Treatment Period

Number of Participants With Adverse Events (Grade 3 or Higher) That Occurred During Follow-Up Period

Peripheral Blood Methemoglobin

Metabolic Complete Response (mCR)

Intensity Modulated Radiation Therapy (IG-IMRT)

Overall Study

Spots Global Cancer Trial Database for unresectable vaginal carcinoma