Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00941070
Other study ID # NCI-2012-02896
Secondary ID NCI-2012-02896CD
Status Completed
Phase Phase 2
First received July 16, 2009
Last updated October 16, 2017
Start date July 2009
Est. completion date July 2012

Study information

Verified date October 2017
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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. 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.


Description:

PRIMARY OBJECTIVES:

I. To determine three-month fasting F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) imaging complete metabolic response as defined by the European Organization for Research and Treatment of Cancer (EORTC) PET study group.

SECONDARY OBJECTIVES:

I. To determine 6-month progression-free survival rate as calculated from the date of first treatment until date of disease progression, relapse, or death.

II. To quantitate change in pre-treatment standard uptake value (SUV) on PET/CT and post-treatment PET/CT or disease progression PET/CT.

III. To quantitate pre-treatment, during treatment and 3-mo 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 December 31, 2010; CTCAE v4.0 will be utilized beginning January 1, 2011.

IV. To associate smoking habit (non-smoker, smoker who quit during therapy, smoker) with 3-mo post-treatment PET/CT metabolic response and 3-mo best overall clinical response as measured by RECIST criteria after Triapine®, cisplatin, and radiation therapy.

V. To associate HPV or non-HPV sub-type cervical cancer with 3-mo post-treatment PET/CT metabolic response and 3-mo best overall clinical response as measured by RECIST criteria after Triapine®, cisplatin, and radiation therapy.

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.


Recruitment information / eligibility

Status Completed
Enrollment 26
Est. completion date July 2012
Est. primary completion date April 2012
Accepts healthy volunteers No
Gender Female
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Female patients must have histologically confirmed (tumor tissue biopsy) primary clinical stage IB2-IVB cervical cancer or clinical stage II-IVB vaginal cancer not amenable to curative surgical resection alone to be eligible; patients with stage IVB cervical cancer may receive systemic chemotherapy for treatment of metastatic disease a) after the 3-month post-therapy PET scan and b) if the 3-month post-therapy PET scan documents progressive disease at the discretion of the treating physician

- Patients with other active invasive malignancies are excluded; patients with prior malignancies (except non-melanoma skin cancer or prior in situ carcinoma of the cervix, patients with synchronous or past history of primary endometrial cancer meeting all conditions of a) stage not greater than IB, b) no more than superficial myometrial invasion, c) without vascular or lymphatic invasion, and d) no poorly differentiated subtypes including papillary serous, clear cell or other FIGO grade 3 lesions; patients with other invasive malignancies who had (or have) cancer present within the last five years are excluded; patients are excluded if they have received prior low abdominal or pelvic radiotherapy for any reason that would contribute radiation dose that would exceed tolerance of normal tissues

- Life expectancy of greater than 3 months

- 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; patients eligible for cisplatin chemotherapy using the criteria for creatinine clearance may also receive intravenous Triapine®

- Women of child-bearing potential and male partners 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

- Patients must demonstrate ability to understand and the 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 neurological dysfunction that would confound the evaluation of neurological 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 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 as the antidote methylene blue for Triapine® toxicity may be at best ineffective in such patients and may have the potential to complicate the clinical situation by provoking hemolysis

- Pregnant women are excluded from this study because Triapine® is a heterocyclic carboxaldehyde thiosemicarbazone with the potential for teratogenic or abortifacient effects; screening beta-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

- Patients not willing to agree to use appropriate contraception while on trial will be excluded

- 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; HIV testing is not mandatory; patients that are known to be HIV-positive are ineligible if they are receiving combination antiretroviral therapy

Study Design


Intervention

Drug:
triapine
Given IV
cisplatin
Given IV
Radiation:
external beam radiation therapy
Undergo pelvic external beam radiation therapy
Procedure:
quality-of-life assessment
Ancillary studies
Other:
questionnaire administration
Ancillary studies
Radiation:
fludeoxyglucose F 18
Undergo FDG-PET/CT
Procedure:
positron emission tomography
Undergo FDG-PET/CT
computed tomography
Undergo FDG-PET/CT

Locations

Country Name City State
United States Case Western Reserve University Cleveland Ohio

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Fasting F-18 Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET/CT) Imaging Complete Metabolic Response, Reported Following National Cancer Institute (NCI) and European Organization for Research and Treatment of Cancer (EORTC) Guidelines. To quantitate change in pre-treatment standard uptake value (SUV) on PET/CT and posttreatment PET/CT or disease progression PET/CT. Change in PET/CT SUV will be associated with 3-month best overall clinical response. post therapy at 3 months
Secondary Clinical and Objective Response Assignment Number of patients with a complete clinical responses defined as disappearance of all target lesions. A complete metabolic response on PET/CT will be defined as absence of abnormal FDG uptake at sites of abnormal FDG uptake noted on pre-treatment FDG-PET study. post therapy at 3 months
Secondary Clinical and Objective Response Assignment Number of patients with a complete clinical responses defined as disappearance of all target lesions. A complete metabolic response on PET/CT will be defined as absence of abnormal FDG uptake at sites of abnormal FDG uptake noted on pre-treatment FDG-PET study. one month follow up assessment
Secondary Clinical and Objective Response Assignment Number of patients with a complete clinical responses defined as disappearance of all target lesions. A complete metabolic response on PET/CT will be defined as absence of abnormal FDG uptake at sites of abnormal FDG uptake noted on pre-treatment FDG-PET study. three month follow up assessment
Secondary Percent of Patients With Incidence of Grade 2 or Higher Gastrointestinal and Genitourinary Toxicity, Assessed Using CTCAE v3.0 Until December 31, 2010 and CTCAE v4.0 Beginning January 1, 2011 Information will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen. Frequency tables will be constructed to summarize observed incidence by severity and type of toxicity. After 5 weeks of radiation therapy
Secondary Progression-free Survival Percentage of patients that did not have disease progression. Estimates of progression-free survival will be computed using the product-limit estimate of Kaplan and Meier. at 18 months from study entry
Secondary PET/CT Scan Metabolic Activity Descriptive tabular data reporting mean, standard deviation, minimum, maximum provided by metabolic response cohort. Status of 3-month post-treatment metabolic response associated with clinical response measured by RECIST criteria and with overall clinical outcome. Kaplan-Meier (product-limit) method of survival estimation used. Tests of equivalence of the estimates compared using the Wilcoxon long-rank test using P 0.05. Cox proportional hazards regression models used in multivariate analyses. Baseline (pre-therapy)
Secondary PET/CT Scan Metabolic Activity Descriptive tabular data reporting mean, standard deviation, minimum, maximum provided by metabolic response cohort. Status of 3-month post-treatment metabolic response associated with clinical response measured by RECIST criteria and with overall clinical outcome. Kaplan-Meier (product-limit) method of survival estimation used. Tests of equivalence of the estimates compared using the Wilcoxon long-rank test using P 0.05. Cox proportional hazards regression models used in multivariate analyses. 3 months post-treatment
Secondary PET/CT Scan Metabolic Activity Descriptive tabular data reporting mean, standard deviation, minimum, maximum provided by metabolic response cohort. Status of 3-month post-treatment metabolic response associated with clinical response measured by RECIST criteria and with overall clinical outcome. Kaplan-Meier (product-limit) method of survival estimation used. Tests of equivalence of the estimates compared using the Wilcoxon long-rank test using P 0.05. Cox proportional hazards regression models used in multivariate analyses. Up to 5 years
Secondary Change in Sexual Function, Assessed Using the Sexual Function-Vaginal Changes Questionnaire Baseline to up to 5 years
Secondary Change in Smoking Behavior, Assessed Using the Smoking Questionnaire and Cessation Counseling 18 months from study entry
Secondary Progression Free Survival by HPV Subtype Tabular descriptive data will be presented. HPV sub-type will be associated with treatment related toxicity, clinical response, PET metabolic response, and overall clinical outcome. Kaplan-Meier (product-limit) method of survival estimation will be used. Tests of equivalence of the estimates will be compared using the Wilcoxon long-rank test using a threshold for statistical significance of P 0.05. Cox proportional hazards regression models will be used in multivariate analyses. Baseline
See also
  Status Clinical Trial Phase
Completed NCT00416455 - Fludeoxyglucose (FDG) F 18 PET Scan, CT Scan, and Ferumoxtran-10 MRI Scan Before Chemotherapy and Radiation Therapy in Finding Lymph Node Metastasis in Patients With Locally Advanced Cervical Cancer or High-Risk Endometrial Cancer Phase 1/Phase 2
Completed NCT00054444 - Radiation Therapy and Chemotherapy in Treating Patients With Locally Advanced Cervical Cancer Phase 1
Completed NCT01846520 - Family Caregiver Palliative Care Intervention in Supporting Caregivers of Patients With Stage II-IV Gastrointestinal, Gynecologic, Urologic and Lung Cancers N/A
Completed NCT00068549 - Radiation Therapy Plus Cisplatin and Gemcitabine in Treating Patients With Cervical Cancer Phase 1
Completed NCT00559377 - FDG and FMISO PET Hypoxia Evaluation in Cervical Cancer Phase 2
Completed NCT01079832 - Stereotactic Radiosurgery Using CyberKnife in Treating Women With Advanced or Recurrent Gynecological Malignancies Phase 2
Completed NCT02164461 - Axalimogene Filolisbac (ADXS11-001) High Dose in Women With Human Papillomavirus (HPV) + Cervical Cancer Phase 1
Completed NCT00335998 - 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 Phase 1
Recruiting NCT03469531 - Study of Nimotuzumab Combined With Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer Phase 2
Completed NCT01155258 - Temsirolimus and Vinorelbine Ditartrate in Treating Patients With Unresectable or Metastatic Solid Tumors Phase 1
Completed NCT00897442 - Collecting Tumor Samples From Patients With Gynecological Tumors N/A
Completed NCT01098630 - Patient, Physician, and Nurse Factors Associated With Entry Onto Clinical Trials and Finishing Treatment in Patients With Primary or Recurrent Uterine, Endometrial, or Cervical Cancer
Withdrawn NCT01019278 - Proton Beam Radiation Therapy and Cisplatin in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer and Positive Lymph Nodes Phase 2
Completed NCT02646319 - Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations Early Phase 1
Completed NCT00104910 - Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer Phase 1
Completed NCT00057863 - Oxaliplatin and Paclitaxel in Treating Patients With Locally Recurrent or Metastatic Cervical Cancer Phase 2
Completed NCT01266447 - Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer Phase 2
Terminated NCT00262821 - Cisplatin and Radiation Therapy With or Without Tirapazamine in Treating Patients With Cervical Cancer Phase 3
Completed NCT00107445 - EF5 in Finding Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Cervical, Endometrial, or Ovarian Epithelial Cancer Phase 2
Terminated NCT01992861 - MRI and PET Imaging in Predicting Treatment Response in Patients With Stage IB-IVA Cervical Cancer