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
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| ClinicalTrials.gov Identifier: NCT02466971 |
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Recruitment Status :
Recruiting
First Posted : June 9, 2015
Last Update Posted : April 12, 2021
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Sponsor:
National Cancer Institute (NCI)
Collaborator:
NRG Oncology
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 IV Vaginal Cancer AJCC v6 and v7 Stage IVA Cervical Cancer AJCC v6 and v7 Stage IVA Vaginal Cancer AJCC v6 and v7 Unresectable Vaginal Carcinoma 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 3 |
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| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 450 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Actual Study Start Date : | January 15, 2016 |
| Estimated Primary Completion Date : | July 23, 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Vaginal Cancer
Drug Information available for:
Cisplatin
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Cisplatin
Given IV
Other Names:
Radiation: External Beam Radiation Therapy Undergo EBRT
Other Names:
Radiation: Intensity-Modulated Radiation Therapy Undergo IMRT
Other Names:
Radiation: Internal Radiation Therapy Undergo brachytherapy
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Radiation: Radiation Therapy Undergo conventional RT
Other Names:
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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.
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Drug: Cisplatin
Given IV
Other Names:
Radiation: Intensity-Modulated Radiation Therapy Undergo IMRT
Other Names:
Radiation: Internal Radiation Therapy Undergo brachytherapy
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Radiation: Radiation Therapy Undergo conventional RT
Other Names:
Drug: Triapine Given IV
Other Names:
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Primary Outcome Measures :
- Overall survival (OS) [ Time Frame: Time (in months) since registration (and randomization) onto the study to the 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.
Secondary Outcome Measures :
- Progression-free survival (PFS) [ Time Frame: Time (in months) since registration (and randomization) onto the study to the date of 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.
- Metabolic complete response (mCR) [ Time Frame: Up to 3 months after completion of treatment ]Will be assessed by fludeoxyglucose F-18 (18F-FDG) positron emission tomography (PET)/computed tomography (CT). 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.
- Incidence of acute adverse events [ Time Frame: Up to 30 days after completion of study treatment ]Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. 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.
- 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.
- Incidence of hematologic and gastrointestinal (GI) adverse events [ Time Frame: Up to 30 days after completion of study treatment ]Will be assessed by CTCAE version 4. 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 [ Time Frame: Up to 5 years ]Will be assessed by CTACE version 4. 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.
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 intensity modulated radiation therapy (IG-IMRT) [ Time Frame: Up to 5 years ]Will 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
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
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
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02466971
Locations
Show 376 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
NRG Oncology
Investigators
| Principal Investigator: | Charles A Leath | NRG Oncology |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT02466971 |
| 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 ( U.S. NIH Grant/Contract ) |
| First Posted: | June 9, 2015 Key Record Dates |
| Last Update Posted: | April 12, 2021 |
| Last Verified: | March 2021 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Carcinoma Carcinoma, Squamous Cell Adenocarcinoma Uterine Cervical Neoplasms Vaginal 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 Uterine Cervical Diseases Uterine Diseases Vaginal Diseases Neoplasms, Complex and Mixed Cisplatin Antineoplastic Agents |