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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01835171
First received: April 16, 2013
Last updated: July 18, 2014
Last verified: June 2014
  Purpose

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 or by stopping them from dividing. 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.


Condition Intervention Phase
Cervical Adenocarcinoma
Cervical Adenosquamous Cell Carcinoma
Cervical Squamous Cell Carcinoma
Stage IB Cervical Cancer
Stage II Vaginal Cancer
Stage IIA 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 Squamous Cell Carcinoma
Drug: triapine
Drug: cisplatin
Radiation: external beam radiation therapy
Radiation: brachytherapy
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Study of Intravenous 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone (3-AP, Triapine® NSC #663249) Cisplatin-Radiochemotherapy Versus Intravenous Cisplatin-Radiochemotherapy in Women Diagnosed With Stage IB-IVA Cervical Cancer and Stage II-IVA Vaginal Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 18F-FDG PET/CT metabolic complete response by European Organization for Research and Treatment of Cancer criteria [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Acute (less than 30 day) adverse events, graded according to National Cancer Institute (NCI) CTCAE, version 4 [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]
  • Late (greater than or equal to 30 day) adverse events, graded according to NCI CTCAE v4.0 [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
  • Clinical response as measured by RECIST version 1.1 [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: The time from start of treatment until time of progression, recurrence, or death, assessed up to 6 months ] [ Designated as safety issue: No ]
    Life table analyses as presented by the method of Kaplan and Meier will be used to determine statistical significance using an alpha of 0.05.

  • Methemoglobin percentage after triapine infusion (Optional) [ Time Frame: Up to 24 hours after triapine infusion ] [ Designated as safety issue: No ]

Estimated Enrollment: 73
Study Start Date: April 2013
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (cisplatin, EBRT, brachytherapy)
Patients receive cisplatin IV over 90 minutes on days 2, 9, 16, 23, and 30 of radiation therapy. Patients undergo EBRT five days a week for 5 weeks with a boost in week 6 followed by 5 sessions of HDR brachytherapy once or twice weekly beginning in week 4 or up to 2 sessions of LDR brachytherapy within 3 weeks of completion of EBRT.
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Radiation: external beam radiation therapy
Undergo EBRT
Other Name: EBRT
Radiation: brachytherapy
Undergo HDR or LDR brachytherapy
Other Names:
  • low-LET implant therapy
  • radiation brachytherapy
  • therapy, low-LET implant
Other: laboratory biomarker analysis
Optional correlative studies
Experimental: Arm II (triapine, cisplatin, EBRT, brachytherapy)
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.
Drug: triapine
Given IV
Other Names:
  • 3-AP
  • OCX-191
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Radiation: external beam radiation therapy
Undergo EBRT
Other Name: EBRT
Radiation: brachytherapy
Undergo HDR or LDR brachytherapy
Other Names:
  • low-LET implant therapy
  • radiation brachytherapy
  • therapy, low-LET implant
Other: laboratory biomarker analysis
Optional correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • 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
  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: NCT01835171

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Patricia L. Judson    800-456-7121    canceranswers@moffitt.org   
Principal Investigator: Patricia L. Judson         
United States, Ohio
Summa Akron City Hospital/Cooper Cancer Center Recruiting
Akron, Ohio, United States, 44304
Contact: Vivian E. von Gruenigen    330-379-3514    vongruev@summa-health.org   
Principal Investigator: Vivian E. von Gruenigen         
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Chad M. Michener    216-444-1712    michenc@ccf.org   
Principal Investigator: Chad M. Michener         
Case Western Reserve University Recruiting
Cleveland, Ohio, United States, 44106
Contact: Tracy Sherertz    800-641-2422      
Principal Investigator: Tracy Sherertz         
UHHS-Chagrin Highlands Medical Center Recruiting
Orange Village, Ohio, United States, 44122
Contact: Jerald Katcher    216-896-1755    jerald.katcher@uhhospitals.org   
Principal Investigator: Jerald Katcher         
United States, Oklahoma
University of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Kathleen N. Moore    405-271-8707    kathleen-moore@ouhsc.edu   
Principal Investigator: Kathleen N. Moore         
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Jayanthi S. Lea    214-648-3026    jayanthi.lea@utsouthwestern.edu   
Principal Investigator: Jayanthi S. Lea         
Sponsors and Collaborators
Investigators
Principal Investigator: Charles Kunos Case Western Reserve University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01835171     History of Changes
Other Study ID Numbers: NCI-2013-00804, NCI-2013-00804, NCI 9434, CASE 4812, 9434, P30CA043703, N01CM00070, U01CA062502
Study First Received: April 16, 2013
Last Updated: July 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Vaginal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Vaginal Diseases
Neoplasms, Complex and Mixed
Adenocarcinoma
Carcinoma
Carcinoma, Squamous Cell
Carcinoma, Adenosquamous
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014