Advanced Vaginal Adenocarcinoma, Advanced Vaginal Adenosquamous Carcinoma, Advanced Vaginal Squamous Cell Carcinoma, Cervical Adenocarcinoma, Cervical Adenosquamous Carcinoma, Cervical Squamous Cell Carcinoma, Stage IB2 Cervical Cancer AJCC v6 and v7, Stage IIA Cervical Cancer AJCC v7, Stage IIB Cervical Cancer AJCC v6 and v7, Stage II Cervical Cancer AJCC v7, Stage IIIB Cervical Cancer AJCC v6 and v7, Stage III Vaginal Cancer AJCC v6 and v7, Stage II Vaginal Cancer AJCC v6 and v7, Stage IVA Cervical Cancer AJCC v6 and v7, Stage IVA Vaginal Cancer AJCC v6 and v7, Stage IV Vaginal Cancer AJCC v6 and v7, Unresectable Vaginal Carcinoma, Vaginal Adenocarcinoma, Vaginal Adenosquamous Carcinoma, Vaginal Carcinoma, Vaginal Squamous Cell Carcinoma, Not Otherwise Specified
Conditions
Brief summary
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.
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. (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.
Interventions
Undergo brachytherapy
Given IV
Undergo EBRT
Undergo IMRT
Correlative studies
Undergo conventional RT
Given IV
Sponsors
Study design
Eligibility
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 (FIGO 2009) 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 (05/30/2017) * Patients scheduled to be treated with adjuvant consolidation chemotherapy or other anti-neoplastic therapy at the conclusion of their standard chemoradiation (05/30/2017) * Patients with self-reported or known diagnosis of G6PD deficiency (05/30/2017) * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) Rate at 3 Years | At 3 years from randomization. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Rate at 3 Years | At 3 years from study randomization. | 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 Adverse Events (Grade 3 or Higher) During Treatment Period | During treatment period and up to 30 days after stopping the study treatment with a median treatment time as 53 days ranging from 1 to 189 days. | Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0. |
Countries
Canada, Puerto Rico, United States
Contacts
NRG Oncology
Participant flow
Recruitment details
NRG-GY006 opened to accrual on January 15, 2016, and closed to accrual on September 22, 2022.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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 | 224 |
| 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.
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 | 224 |
| Total | 448 |
Baseline characteristics
| Characteristic | Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Total |
|---|---|---|---|
| Age, Continuous | 47 years | 47 years | 47 years |
| Age, Customized 20-29 years | 7 Participants | 8 Participants | 15 Participants |
| Age, Customized 30-39 years | 58 Participants | 50 Participants | 108 Participants |
| Age, Customized 40-49 years | 64 Participants | 73 Participants | 137 Participants |
| Age, Customized 50-59 years | 57 Participants | 49 Participants | 106 Participants |
| Age, Customized 60-69 years | 27 Participants | 27 Participants | 54 Participants |
| Age, Customized 70-79 years | 9 Participants | 13 Participants | 22 Participants |
| Age, Customized >= 80 years | 2 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 44 Participants | 57 Participants | 101 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 169 Participants | 164 Participants | 333 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 3 Participants | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 8 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants | 36 Participants | 68 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants | 15 Participants | 27 Participants |
| Race (NIH/OMB) White | 165 Participants | 160 Participants | 325 Participants |
| Sex: Female, Male Female | 224 Participants | 224 Participants | 448 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 35 / 224 | 34 / 224 |
| other Total, other adverse events | 198 / 208 | 194 / 202 |
| serious Total, serious adverse events | 45 / 208 | 45 / 202 |
Outcome results
Overall Survival (OS) Rate at 3 Years
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.
Time frame: At 3 years from randomization.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Overall Survival (OS) Rate at 3 Years | 78.1 percentage of participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Overall Survival (OS) Rate at 3 Years | 79.6 percentage of participants |
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period
Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.
Time frame: During treatment period and up to 30 days after stopping the study treatment with a median treatment time as 53 days ranging from 1 to 189 days.
Population: Participants who received any study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Infections and infestations | 17 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Other blood and lymphatic system disorders | 5 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Metabolism and nutrition disorders | 29 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Cardiac disorders | 0 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Musculoskeletal and connective tissue disorders | 2 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Platelet count decreased | 5 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Neoplasms benign, malignant and unspecified | 0 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Eye disorders | 0 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Nervous system disorders | 5 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Anemia | 23 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Psychiatric disorders | 1 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Gastrointestinal disorders | 22 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Renal and urinary disorders | 3 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Neutrophil count decreased | 13 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Reproductive system and breast disorders | 8 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | General disorders | 7 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | White blood cell count decreased | 19 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Skin and subcutaneous tissue disorders | 1 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Hepatobiliary disorders | 1 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Surgical and medical procedures | 1 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Other investigations | 39 Participants |
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Vascular disorders | 20 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Vascular disorders | 11 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Anemia | 18 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Other blood and lymphatic system disorders | 7 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | White blood cell count decreased | 17 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Platelet count decreased | 2 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Neutrophil count decreased | 4 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Other investigations | 41 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Cardiac disorders | 2 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Eye disorders | 1 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Gastrointestinal disorders | 22 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | General disorders | 1 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Hepatobiliary disorders | 0 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Infections and infestations | 12 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Metabolism and nutrition disorders | 22 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Musculoskeletal and connective tissue disorders | 3 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Neoplasms benign, malignant and unspecified | 1 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Nervous system disorders | 4 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Psychiatric disorders | 1 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Renal and urinary disorders | 4 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Reproductive system and breast disorders | 11 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Respiratory, thoracic and mediastinal disorders | 1 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Skin and subcutaneous tissue disorders | 0 Participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period | Surgical and medical procedures | 0 Participants |
Progression-free Survival (PFS) Rate at 3 Years
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.
Time frame: At 3 years from study randomization.
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Cisplatin, IMRT or RT, Brachytherapy) | Progression-free Survival (PFS) Rate at 3 Years | 69.5 percentage of participants |
| Arm II (Cisplatin, IMRT or RT, Brachytherapy, Triapine) | Progression-free Survival (PFS) Rate at 3 Years | 71.4 percentage of participants |
Intensity Modulated Radiation Therapy (IG-IMRT)
Number of Participants with KBP IG-IMRT
Time frame: Up to 60 days.
Metabolic Complete Response (mCR)
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.
Time frame: Up to 3 months after completion of treatment
Number of Participants With Adverse Events (Grade 3 or Higher) That Occurred During Follow-Up Period
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.
Time frame: Up to 5 years
Number of Participants With Hematologic Toxicity During Treatment Period
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.
Time frame: Up to 30 days after completion of study treatment
Peripheral Blood Methemoglobin
Peripheral blood methemoglobin collected at baseline and 1, 3, 5 and 24 hours after Triapine infusion on Day 1 in Arm II.
Time frame: Baseline to 24 hours after triapine infusion