Cisplatin and Radiation Therapy With or Without Triapine in Treating Patients With Previously Untreated Stage IB-IVA Cervical Cancer or Stage II-IVA Vaginal Cancer
Conditions
Cervical Adenocarcinoma - Cervical Adenosquamous Carcinoma - Cervical Squamous Cell Carcinoma - Stage IB2 Cervical Cancer - Stage II Vaginal Cancer - Stage IIA1 Cervical Cancer - Stage IIA2 Cervical Cancer - Stage IIB Cervical Cancer - Stage III Vaginal Cancer - Stage IIIA Cervical Cancer - Stage IIIB Cervical Cancer - Stage IVA Cervical Cancer - Stage IVA Vaginal Cancer - Vaginal Adenocarcinoma - Vaginal Adenosquamous Carcinoma - Vaginal Squamous Cell Carcinoma
Conditions: official terms
Adenocarcinoma - Carcinoma - Carcinoma, Adenosquamous - Carcinoma, Squamous Cell - Uterine Cervical Neoplasms - Vaginal Neoplasms
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Cisplatin Type: Drug
Name: External Beam Radiation Therapy Type: Radiation
Name: Internal Radiation Therapy Type: Radiation
Name: Laboratory Biomarker Analysis Type: Other
Name: Triapine Type: Drug
Overall Status
Recruiting
Summary
This randomized phase II trial studies how well cisplatin and radiation therapy with or without triapine work in treating patients with previously untreated stage IB-IVA cervical cancer or stage II-IVA vaginal cancer. 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. Radiation therapy uses high energy x rays to kill tumor cells. Triapine may make tumor cells more sensitive to radiation therapy. It is not yet known whether cisplatin and radiation therapy is more effective when given with or without triapine in treating cervical or vaginal cancer.
Detailed Description
PRIMARY OBJECTIVES:

I. To determine the posttherapy 3-month fludeoxyglucose F 18 (18F-FDG) positron emission tomography (PET)/computed tomography (CT) complete metabolic response of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) (triapine) radiochemotherapy.

SECONDARY OBJECTIVES:

I. Determining acute < 30 day adverse events of 3-AP radiochemotherapy by Common Terminology Criteria for Adverse Events (CTCAE), version 4.

II. Determining the late >= 30 day adverse events of 3-AP radiochemotherapy by CTCAE version 4.

III. Determining post-therapy clinical response by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.

IV. Determining the progression-free interval of 3-AP radiochemotherapy. V. Determining peripheral blood methemoglobin proportion before and after 3-AP infusion. (Optional)

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, and 30 of radiation therapy. Patients undergo external beam radiation therapy (EBRT) five days a week for 5 weeks with a boost in week 6 followed by 5 sessions of high dose rate (HDR) brachytherapy once or twice weekly beginning in week 4 or up to 2 sessions of low dose rate (LDR) brachytherapy within 3 weeks of completion of EBRT.

ARM II: Patients receive triapine IV over 90-120 minutes on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33 of radiation therapy. Patients also receive cisplatin IV and undergo EBRT and brachytherapy as in Arm I.

In both arms, treatment continues for up to 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1, 3, and 6 months.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Female
Criteria: Inclusion Criteria:

- Patients are eligible with untreated squamous, adenosquamous, or adenocarcinoma cancers of stage IB2-IVA carcinoma of the uterine cervix or stage II-IVA vaginal carcinoma not amenable to curative surgical resection; pathological verification of diagnosis must be obtained and recorded; 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 for participation; the patient must be able to tolerate the requirements for 18F-FDG PET/CT scanning

- Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2

- Patients must have a life expectancy of greater than 20 weeks

- Absolute neutrophil count > 1,500/µL

- Platelets > 100,000/µL

- 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

- Creatinine =< 1.5 mg/dL to receive weekly intravenous cisplatin*; *patients whose serum creatinine is between 1.5 and 1.9 mg/dL are eligible for cisplatin if the estimated creatinine clearance is >= 30 ml/min; for the purpose of estimating the creatinine clearance, the formula of Cockcroft and Gault for females should be used

- All patients must have measurable cervical cancer or vaginal cancer disease; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 40 mm when measured preferably by clinical exam or alternatively by computed tomography (CT), magnetic resonance imaging (MRI)

- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; if in the investigator's opinion the patient is of child-bearing age, a negative urine pregnancy test must be resulted within 7 days before initiating protocol therapy; women should not breast feed during therapy (or has agreed to discontinue breastfeeding before initiation of therapy)

- Patients must have an ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

- Patients with other active invasive malignancies are excluded; patients with prior malignancies are excluded (except non-melanoma skin cancer or prior in situ carcinoma of the cervix; patients with other invasive malignancies who had [or have] cancer present within the last five years); 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

- Patients who are receiving any other investigational agents

- Patients with known brain metastases should be excluded from this clinical trial

- History of allergic reactions attributed to compounds of similar chemical or biologic composition to 3-AP (triapine) or other agents used in study

- 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, known inadequately controlled hypertension, significant pulmonary disease including dyspnea at rest, 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 are excluded

- Patient does not have uncontrolled diabetes mellitus (fasting blood glucose > 200 mg/dL)

- Patients with known glucose-6-phosphate dehydrogenase deficiency (G6PD) are excluded due to an inability to administer the antidote for methemoglobinemia, methylene blue; testing for G6PD is not required for study enrollment and optional

- Known human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy are ineligible; HIV testing is not required for study enrollment and optional
Locations
Moffitt Cancer Center
Tampa, Florida, United States
Status: Recruiting
Contact: Mian M. Shahzad - 800-456-7121 - canceranswers@moffitt.org
Summa Akron City Hospital/Cooper Cancer Center
Akron, Ohio, United States
Status: Recruiting
Contact: Charles A. Kunos - 330-375-6101
UHHS-Chagrin Highlands Medical Center
Beachwood, Ohio, United States
Status: Recruiting
Contact: Tracy Sherertz - 800-641-2422
Case Western Reserve University
Cleveland, Ohio, United States
Status: Recruiting
Contact: Rodney J. Ellis - 800-641-2422
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Status: Recruiting
Contact: Chad M. Michener - 216-444-1712 - michenc@ccf.org
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Status: Recruiting
Contact: Kathleen N. Moore - 405-271-4272 - julie-traylor@ouhsc.edu
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States
Status: Recruiting
Contact: Jayanthi S. Lea - 214-648-3026 - jayanthi.lea@utsouthwestern.edu
Start Date
April 2013
Sponsors
National Cancer Institute (NCI)
Source
National Cancer Institute (NCI)
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page