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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00335998
First received: June 8, 2006
Last updated: January 10, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
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
Drug: triapine
Other: laboratory biomarker analysis
Radiation: external beam radiation therapy
Radiation: brachytherapy
Drug: cisplatin
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Toxicity of radiotherapy and Triapine® combination therapy as documented by dose-limiting toxicities (DLTs) using Common Terminology Criteria for Adverse Events (CTCAE) criteria, version 3.0 [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: Yes ]
  • MTD of Triapine® when given in combination with pelvic radiotherapy with or without weekly intravenous cisplatin chemotherapy [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • RR R2 enzyme quantity [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Paired T-tests will be used to compare RR R2 enzyme quantity and activity before and after treatment. %MHgb levels will be tracked over time with corresponding pharmacokinetic and biopsy analyses and tested for time course correlations with plasma Triapine® concentrations.

  • RR R2 enzyme quantity [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
    Paired T-tests will be used to compare RR R2 enzyme quantity and activity before and after treatment. %MHgb levels will be tracked over time with corresponding pharmacokinetic and biopsy analyses and tested for time course correlations with plasma Triapine® concentrations.


Enrollment: 24
Study Start Date: March 2006
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (triapine)

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.

Drug: triapine
Given IV
Other Names:
  • 3-AP
  • OCX-191
Other: laboratory biomarker analysis
Correlative studies
Radiation: external beam radiation therapy
Undergo external beam radiation therapy
Other Name: EBRT
Radiation: brachytherapy
Undergo intracavitary or interstitial brachytherapy
Other Names:
  • low-LET implant therapy
  • radiation brachytherapy
  • therapy, low-LET implant
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Patients with pathologically-proven primary or recurrent locally advanced cervical, vaginal, or vulvar cancers not amenable to curative surgical resection alone are eligible
  • Patients with pathologically-proven recurrent or persistent epithelial ovarian or endometrial cancer a) not amenable to curative surgical resection alone, b) are planned for pelvic radiotherapy, and c) are amenable to tumor biopsy through the vaginal canal are eligible
  • Patients with other active invasive malignancies are excluded; patients with prior malignancies in remission for at least six months and not being currently treated are eligible; patients are excluded if their previous cancer treatment as determined by their treating physicians contraindicates this protocol therapy or if they have received prior low abdominal or pelvic radiotherapy that would contribute radiation dose that would exceed tolerance of normal tissues (as determined by the principal investigator or co-investigators); for patients relapsing at least four weeks after initial surgery or chemotherapy, they must have fully recovered from side effects of prior treatment, have measurable disease in the pelvis; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques (CT, MRI, x-ray or as >= 10 mm with spiral CT scan; patients with metastatic disease to extra-pelvic sites are eligible if pelvic radiotherapy is planned as primary management of the site of pelvic disease. There is no numerical limit on prior chemotherapy regimens previously received
  • ECOG performance status 0-2; (Karnofsky >= 50%)
  • Life expectancy of greater than 3 months
  • Leukocytes >= 3,000/uL
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 100,000/uL
  • Hemoglobin >= 10 g/dL
  • Total bilirubin =< 2.0 mg/dL
  • AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
  • PT/aPTT =< 1.5 X institutional upper limit of normal
  • Patients should have a serum creatinine =< 1.5mg/dL to receive weekly intravenous cisplatin chemotherapy; patients whose serum creatinine is between 1.5 and 1.9 mg/dL are eligible for cisplatin chemotherapy if the estimated creatinine clearance is >= 30 ml/min; for the purpose of estimating the creatinine clearance, the formula of Jelliffe should be used: CCr = 0.9{98-[0.8(age-20)]}/Scr where CCr is the estimated creatinine clearance, age is patient's age in years (from 20-80), and Scr is the serum creatinine in mg/dL; patients eligible for cisplatin chemotherapy will also receive intravenous Triapine®; patients who have refused or are not candidates for cisplatin chemotherapy as defined above, have prior platinum adverse sensitivity, have active neuropathy, or have intercurrent co-morbid illness as determined by treating physicians will receive intravenous Triapine® alone with pelvic radiation; to receive Triapine® alone with pelvic radiotherapy, patients must have a serum creatinine =< 2.0mg/dL
  • The effects of Triapine® on the developing human fetus are unknown; for this reason and because heterocyclic carboxaldehyde thiosemicarbazones as well as other therapeutic agents used in this trial are known to be teratogenic, 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
  • Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of Triapine® will be determined following review of their case by the Principal Investigator
  • Ability to undergo and the willingness to sign a written informed consent for placement of a PICC line or a central venous catheter
  • Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are excluded
  • Patients may not be 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 Triapine® or other agents used in study
  • Patients unable to receive intravenous chemotherapies as a consequence of poor vascular access (for example, patient receiving hemodialysis) are ineligible
  • Uncontrolled intercurrent illness including, but not limited to, 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 > 2mg/dL), or psychiatric illness/social situations that would limit compliance with study requirements are excluded
  • Patients with known glucose-6-phosphate dehydrogenase deficiency (G6PD) are excluded
  • Pregnant women are excluded from this study because Triapine® is a heterocyclic carboxaldehyde thiosemicarbazone with the potential for teratogenic or abortifacient effects; screening b-hcg levels and diagnostic tests will be used to determine eligibility; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Triapine®, breastfeeding should be discontinued if the mother is treated with Triapine®; these potential risks may also apply to other agents used in this study
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Triapine®; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  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: NCT00335998

Locations
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
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: NCT00335998     History of Changes
Other Study ID Numbers: NCI-2012-03126, CASE 1805, U01CA062502
Study First Received: June 8, 2006
Last Updated: January 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Vaginal Neoplasms
Vulvar Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Vulvar Diseases
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Vaginal Diseases
Ovarian Diseases
Adnexal Diseases
Endocrine System Diseases
Gonadal Disorders
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 28, 2014