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Radiation Therapy and Cisplatin With or Without Triapine in Treating Patients With Newly Diagnosed Stage IB2, II, or IIIB-IVA Cervical Cancer or Stage II-IVA Vaginal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02466971
First received: June 5, 2015
Last updated: April 24, 2017
Last verified: April 2017
  Purpose
This randomized phase II 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.

Condition Intervention Phase
Cervical Adenocarcinoma
Cervical Adenosquamous Carcinoma
Cervical Squamous Cell Carcinoma, Not Otherwise Specified
Stage IB2 Cervical Cancer
Stage II Cervical Cancer
Stage II Vaginal Cancer
Stage IIA Cervical Cancer
Stage IIB Cervical Cancer
Stage III Vaginal Cancer
Stage IIIB Cervical Cancer
Stage IVA Cervical Cancer
Stage IVA Vaginal Cancer
Stage IVB Vaginal Cancer
Vaginal Adenocarcinoma
Vaginal Adenosquamous Carcinoma
Vaginal Squamous Cell Carcinoma, Not Otherwise Specified
Drug: Cisplatin
Radiation: External Beam Radiation Therapy
Radiation: Intensity-Modulated Radiation Therapy
Radiation: Internal Radiation Therapy
Other: Laboratory Biomarker Analysis
Radiation: Radiation Therapy
Drug: Triapine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Randomized Phase II 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Time (in months) since registration to date first documented recurrence/progression, death or last follow-up visit (contact), assessed up to 5 years ]
    Product-limit estimates according to the method of Kaplan and Meier and the one sided log-rank test (alpha = 0.1) will be used to compare survival endpoint (PFS) between treatment arms. In addition, adjusted hazard ratios and respective 95% confidence intervals will be calculated using the Cox proportional hazards regression model.


Secondary Outcome Measures:
  • Incidence of acute adverse events as assessed by CTCAE version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ]
    The frequency and severity of adverse events will be assessed. Maximum grade of adverse effect will be tabulated for each adverse event and significance of observed differences between treatments arms within each adverse event category will be assessed using Chi-square or Fishers' exact test.

  • Incidence of chronic or late adverse events assessed by CTACE version 4 [ Time Frame: Up to 5 years ]
    The frequency and severity of adverse events will be assessed. Maximum grade of adverse effect will be tabulated for each adverse event and significance of observed differences between treatments arms within each adverse event category will be assessed using Chi-square or Fishers' exact test.

  • Incidence of hematologic and GI adverse events assessed by CTCAE version 4 [ Time Frame: Up to 30 days after completion of study treatment ]
    The frequency and severity of adverse events will be assessed. Maximum grade of adverse effect will be tabulated for each adverse event and significance of observed differences between treatments arms within each adverse event category will be assessed using Chi-square or Fishers' exact test.

  • Metabolic complete response (mCR) assessed by 18F-FDG PET/CT [ Time Frame: Up to 3 months after completion of treatment ]
    Frequency of mCR will be tabulated and the probability of attaining a mCR will be estimated. Differences in mCR rate between treatment arms will be assessed using either the Chi-square or Fisher's exact test. The relationship between patients' mCR status at T1 (yes or no) and PFS (and/or OS) will be assessed using regression models to facilitate evaluation of mCR as secondary short term endpoint for patient outcome.

  • Overall survival (OS) [ Time Frame: Time (in months) since registration to date death or last contact, assessed up to 5 years ]
    Product-limit estimates according to the method of Kaplan and Meier and the one sided log-rank test (alpha = 0.1) will be used to compare survival endpoint (OS) between treatment arms. In addition, adjusted hazard ratios and respective 95% confidence intervals will be calculated using the Cox proportional hazards regression model.

  • Treatment compliance (amount of radiation, cisplatin and triapine administered, incidence and duration of treatment delays, reason for delays, and reason why off study therapy) [ Time Frame: Up to 5 years ]
    Treatment compliance will be evaluated and reported.


Other Outcome Measures:
  • Changes in the proportion of peripheral blood methemoglobin [ Time Frame: Baseline to 24 hours after triapine infusion ]
    Difference in peak or in trend of blood methemoglobin levels before and after triapine infusion will be assessed using two tailed paired T-test at alpha = 0.05 significance level. Depending on the observed within subjects correlation, repeated measures analysis of variance may be utilized instead.

  • Type of IG-IMRT [ Time Frame: Up to 5 years ]
    Will explore whether KBP can improve IG-IMRT plans compared to plans that would have been delivered without KBP, estimate the resulting toxicity reduction using NTCP models, and determine whether KBP should be a requirement for future IG-IMRT protocols


Estimated Enrollment: 188
Study Start Date: January 2016
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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.
Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Radiation: External Beam Radiation Therapy
Undergo EBRT
Other Names:
  • Definitive Radiation Therapy
  • EBRT
  • External Beam Radiotherapy
  • External Beam RT
  • external radiation
  • External Radiation Therapy
  • external-beam radiation
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
Radiation: Internal Radiation Therapy
Undergo brachytherapy
Other Names:
  • BRACHYTHERAPY
  • Internal Radiation
  • Internal Radiation Brachytherapy
  • Radiation Brachytherapy
Other: Laboratory Biomarker Analysis
Correlative studies
Radiation: Radiation Therapy
Undergo conventional RT
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RADIATION
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
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 90 minutes 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.
Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
Radiation: Internal Radiation Therapy
Undergo brachytherapy
Other Names:
  • BRACHYTHERAPY
  • Internal Radiation
  • Internal Radiation Brachytherapy
  • Radiation Brachytherapy
Other: Laboratory Biomarker Analysis
Correlative studies
Radiation: Radiation Therapy
Undergo conventional RT
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RADIATION
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
Drug: Triapine
Given IV
Other Names:
  • 3-aminopyridine-2-carboxaldehyde thiosemicarbazone
  • 3-AP
  • 3-Apct
  • OCX-191

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has a new, unrated histologic diagnosis of stage IB2 (> 5 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; 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
  • 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; proteinuria 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 must 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 at the conclusion of their standard chemoradiation
  • Patients with self-reported or known diagnosis of G6PD deficiency
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02466971

  Show 321 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Charles Leath NRG Oncology
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02466971     History of Changes
Obsolete Identifiers: NCT01835171
Other Study ID Numbers: NCI-2015-00835
NCI-2015-00835 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GY006
NRG-GY006 ( Other Identifier: NRG Oncology )
NRG-GY006 ( Other Identifier: CTEP )
U10CA180868 ( US NIH Grant/Contract Award Number )
Study First Received: June 5, 2015
Last Updated: April 24, 2017

Additional relevant MeSH terms:
Vaginal Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Vaginal Diseases
Carcinoma
Carcinoma, Squamous Cell
Adenocarcinoma
Uterine Cervical Neoplasms
Carcinoma, Adenosquamous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms, Complex and Mixed
Cisplatin
Succinylcholine
Antineoplastic Agents
Neuromuscular Depolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 26, 2017