Phase I Study of Intravenous Triapine (IND # 68338) in Combination With Pelvic Radiation Therapy With or Without Weekly Intravenous Cisplatin Chemotherapy for Locally Advanced Cervical, Vaginal, or Pelvic Gynecologic Malignancies

Recurrent Ovarian Epithelial Cancer Clinical Trial

Official title: Phase I Study of Intravenous Triapine® (IND #68338) in Combination With Pelvic Radiation Therapy With or Without Weekly Intravenous Cisplatin Chemotherapy for Locally Advanced Cervical, Vaginal, or Pelvic Gynecologic Malignancies.

Status Completed

Clinical Trial Summary

Drugs used in chemotherapy, such as 3-AP and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 3-AP may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. 3-AP and cisplatin may make tumor cells more sensitive to radiation therapy. Giving 3-AP and external-beam radiation therapy together with cisplatin may kill more tumor cells. This phase I trial is studying the side effects and best dose of 3-AP when given together with external-beam radiation therapy with or without cisplatin in treating patients with gynecologic cancer

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of Triapine® when given in combination with pelvic radiotherapy with or without weekly intravenous cisplatin chemotherapy.

II. To determine the dose limiting toxicity (DLT) of Triapine® when given in combination with pelvic radiotherapy with or without weekly intravenous cisplatin chemotherapy.

III. To determine the safety and sequelae of intravenous Triapine® when given in combination with pelvic radiotherapy with or without weekly intravenous cisplatin chemotherapy.

SECONDARY OBJECTIVES:

I. Evaluation of intravenous Triapine®'s targeted inhibition of ribonucleotide reductase through tumor tissue biopsy at pretreatment evaluation and during external beam radiotherapy (Day 10).

II. Serial monitoring of methemoglobin levels during therapy given Triapine®'s iron chelating properties.

OUTLINE: This is a multicenter, dose-escalation study of 3-AP. Patients are assigned to 1 of 2 treatment groups based on eligibility* to receive cisplatin (yes vs no).

NOTE: *Patients who refuse or are not candidates for cisplatin chemotherapy due to prior platinum adverse sensitivity, active neuropathy, or comobid illness, as determined by the treating physician, are eligible to receive 3-AP alone with pelvic radiotherapy.

Group 1: Patients undergo external-beam pelvic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients also receive 3-AP IV over 2 hours on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33 and cisplatin IV over 1½ hours on day 2, 9, 16, 23, and 30.

Group 2: Patients undergo external-beam pelvic radiotherapy and receive 3-AP as in group 1.

In both groups, patients undergo intracavitary or interstitial brachytherapy at least once weekly for 3-5 weeks during or after external-beam radiotherapy as per standard of care.

Cohorts of 3-6 patients in group 1 and 1-3 patients in group 2 receive escalating doses of 3-AP until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

Patients undergo blood draws on days 1 and 10 before treatment with 3-AP and at 2, 4, 6, and 24 hours after starting treatment to assess methemoglobin levels and 3-AP plasma levels. Patients also undergo punch biopsy on days 1 and 10 to determine R2 protein levels by Western blot analysis, ribonucleotide reductase R2 protein levels by flow cytometry, and cytidine deoxyphosphate reductase assay.

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

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study. ;

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms, Glandular and Epithelial
• Ovarian Neoplasms
• Recurrent Cervical Cancer
• Recurrent Ovarian Epithelial Cancer
• Recurrent Vaginal Cancer
• Recurrent Vulvar Cancer
• Stage III Vaginal Cancer
• Stage IIIA Cervical Cancer
• Stage IIIA Ovarian Epithelial Cancer
• Stage IIIA Vulvar Cancer
• Stage IIIB Cervical Cancer
• Stage IIIB Ovarian Epithelial Cancer
• Stage IIIB Vulvar Cancer
• Stage IIIC Ovarian Epithelial Cancer
• Stage IIIC Vulvar Cancer
• Stage IV Ovarian Epithelial Cancer
• Stage IVA Cervical Cancer
• Stage IVA Vaginal Cancer
• Stage IVB Cervical Cancer
• Stage IVB Vaginal Cancer
• Uterine Cervical Neoplasms
• Vaginal Neoplasms
• Vulvar Neoplasms

• NCT number: NCT00335998
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 1
• Start date: March 2006