Triapine, Cisplatin, and Radiation Therapy in Treating Patients With Cervical Cancer or Vaginal Cancer - Full Text View

Sponsor:	Case Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by (Responsible Party):	Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00941070

Purpose

RATIONALE: Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Giving triapine together with cisplatin may make tumor cells more sensitive to radiation therapy.

PURPOSE: This phase II trial is studying how triapine and cisplatin given together with radiation therapy works in treating patients with cervical cancer or vaginal cancer.

Condition	Intervention	Phase
Cervical Cancer Therapy-related Toxicity Vaginal Cancer	Drug: cisplatin Drug: triapine Other: questionnaire administration Procedure: assessment of therapy complications Procedure: computed tomography Procedure: quality-of-life assessment Radiation: fludeoxyglucose F 18 Radiation: radiation therapy	Phase 2

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 2 Study of Triapine® (NSC #663249) and Cisplatin in Combination With Pelvic Radiation for Treatment of Stage IB2-IVa Cervical Cancer or Stage II-IV Vaginal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Cervical Cancer Vaginal Cancer

Drug Information available for: Cisplatin Fludeoxyglucose F 18

U.S. FDA Resources

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:

Fasting F-18 fluorodeoxyglucose PET/CT imaging complete metabolic response [ Time Frame: at 3 months after completion of radiotherapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-free survival [ Time Frame: at 3 months after completion of study treatment, and at disease progression. After completion of study treatment, patients are followed periodically for up to 5 years. ] [ Designated as safety issue: No ]
Fasting PET/CT imaging pre-treatment, 3 months after treatment, and at disease progression [ Time Frame: 3 months after treatment, and at disease progression ] [ Designated as safety issue: No ]
Best overall response as measured by RECIST criteria [ Time Frame: at 3 months ] [ Designated as safety issue: No ]
Relationship between toxicity (i.e., GI and GU toxicity by CTCAE v3.0) and perceived health status as assessed by Sexual Function-Vaginal Changes Questionnaire [ Time Frame: at pre-treatment, 3 months after treatment, and at disease progression ] [ Designated as safety issue: Yes ]

Enrollment:	26
Study Start Date:	June 2009
Estimated Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Intervention Details:

cisplatin IV over 90 minutes on days 2, 9, 16, 23, and 30

triapine IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33

at baseline, at 3 months after completion of study treatment, and at disease progression.

pre-treatment, during treatment, and 3-month post-treatment

at baseline, at 3 months after completion of study treatment, and at disease progression.

at pre-treatment, 3-month post-treatment, and disease progression follow-ups

whole-body F-18 fluorodeoxyglucose-PET/CT imaging at baseline, at 3 months after completion of study treatment, and at disease progression.

Pelvic external beam radiotherapy 5 days a week during weeks 1-5. Patients may undergo parametrial boost radiation and intracavitary low-dose or high-dose rate brachytherapy as clinically indicated.

Detailed Description:

OBJECTIVES:

Primary

To determine 3-month fasting F-18 fluorodeoxyglucose PET/CT imaging complete metabolic response as defined by the European Organization for Research and Treatment of Cancer PET study group in patients with stage IB2-IVA cervical cancer or stage II-IV vaginal cancer treated with triapine, cisplatin, and pelvic radiotherapy.

Secondary

To determine 6-month progression-free survival rate as calculated from the date of first treatment until date of disease progression, relapse, or death.
To quantitate change in pre-treatment standard uptake value on PET/CT and post-treatment PET/CT or disease progression PET/CT and to associate this change with 3-month best overall clinical response as measured by RECIST criteria.
To quantitate pre-treatment, during treatment and 3-month post-treatment grade 2 or higher gastrointestinal,genitourinary, and sexual function toxicity resulting from Triapine, cisplatin and radiation therapy as measured by CTCAE v3.0, which will be utilized until Dec. 31, 2010; CTCAE v4.0 will be utilized beginning Jan. 1, 2011. Validated, self-administered quality of life questionnaires for sexual health [Female Sexual Function Index] will be done at pre-treatment, 3-month post-treatment, and disease progression follow-ups.
To associate smoking habit (non-smoker, smoker who quit during therapy, or smoker) with 3-month post-treatment PET/CT metabolic response and 3-month best overall clinical response as measured by RECIST criteria.
To associate HPV or non-HPV subtype cervical cancer with 3-month post-treatment PET/CT metabolic response and 3-month best overall clinical response as measured by RECIST criteria.

OUTLINE: This is a multicenter study. Patients are stratified according to brachytherapy treatment (planned intracavitary brachytherapy vs none).

Patients receive cisplatin IV over 90 minutes on days 2, 9, 16, 23, and 30 and triapine IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33. Patients also undergo pelvic external beam radiotherapy 5 days a week during weeks 1-5. Patients may undergo parametrial boost radiation and intracavitary low-dose or high-dose rate brachytherapy as clinically indicated.

Patients undergo whole-body F-18 fluorodeoxyglucose-PET/CT imaging at baseline, at 3 months after completion of study treatment, and at disease progression. Patients complete Sexual Function-Vaginal Changes Questionnaire and a smoking behavior questionnaire at baseline, at 3 months after completion of study treatment, and at disease progression.

After completion of study treatment, patients are followed periodically for up to 5 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed (tumor-tissue biopsy) diagnosis of 1 of the following:
- Primary clinical stage IB2-IV cervical cancer
- Clinical stage II-IV vaginal cancer
Not amenable to curative surgical resection alone
No known brain metastases

PATIENT CHARACTERISTICS:

Gynecologic Oncology Group performance status (PS) 0-2 OR Karnofsky PS 60-100%
Life expectancy > 3 months
Leukocytes ≥ 3,000/mm^3
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 10 g/dL
Total bilirubin ≤ 2.0 mg/dL
AST/ALT ≤ 2.5 times upper limit of normal (ULN)
PT/activated PTT ≤ 1.5 times ULN
Serum creatinine ≤ 1.5 mg/dL OR serum creatinine 1.5-1.9 mg/dL and creatinine clearance ≥ 30 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception before and during study treatment
Able to receive intravenous chemotherapies (no poor vascular access)
No uncontrolled concurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- 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)
- Psychiatric illness or social situations that would limit compliance with study requirements
No known glucose-6-phosphate dehydrogenase deficiency
No prior malignancies within the past 5 years except for any of the following:
- Nonmelanoma skin cancer
- Carcinoma in situ of the cervix
- Synchronous or history of primary endometrial cancer meeting all the following:
  - Stage ≤ IB
  - No more than superficial myometrial invasion
  - No vascular or lymphatic invasion
  - No poorly differentiated subtypes including papillary serous, clear cell, or other FIGO grade 3 lesions
No other active invasive malignancies
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to triapine or other agents used in this study

PRIOR CONCURRENT THERAPY:

No prior low abdominal or pelvic radiotherapy for any reason that would contribute to a radiation dose that would exceed the tolerance of normal tissues
More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
No concurrent combination antiretroviral therapy in HIV-positive patients
No other concurrent investigational agents
No other concurrent therapies administered with the intent to treat this cancer

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00941070

Locations

United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106

Sponsors and Collaborators

Case Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Charles Kunos, MD, PhD	Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Principal Investigator:	Peter Rose, MD	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided by Case Comprehensive Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chao J, Synold TW, Morgan RJ Jr, Kunos C, Longmate J, Lenz HJ, Lim D, Shibata S, Chung V, Stoller RG, Belani CP, Gandara DR, McNamara M, Gitlitz BJ, Lau DH, Ramalingam SS, Davies A, Espinoza-Delgado I, Newman EM, Yen Y. A phase I and pharmacokinetic study of oral 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in the treatment of advanced-stage solid cancers: a California Cancer Consortium Study. Cancer Chemother Pharmacol. 2012 Mar;69(3):835-43. Epub 2011 Nov 22.

Responsible Party:	Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00941070 History of Changes
Other Study ID Numbers:	CASE11808, P30CA043703, CASE11808, CASE 11808-CC700
Study First Received:	July 16, 2009
Last Updated:	November 30, 2011
Health Authority:	United States: Federal Government

Keywords provided by Case Comprehensive Cancer Center:

therapy-related toxicity
stage IB cervical cancer
stage IIA cervical cancer
stage IIB cervical cancer
stage III cervical cancer
stage IVA cervical cancer

stage II vaginal cancer
stage III vaginal cancer
stage IVA vaginal cancer
stage IVB vaginal cancer
recurrent vaginal cancer
recurrent cervical cancer

Additional relevant MeSH terms:

Uterine Cervical Neoplasms
Vaginal Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases

Genital Diseases, Female
Vaginal Diseases
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 24, 2012