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

Cervical Adenocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01835171
• Other study ID #: NCI-2013-00804
• Secondary ID: NCI-2013-00804NC
• Status: Active, not recruiting
• Phase: Phase 2
• First received: April 16, 2013
• Last updated: March 25, 2016
• Start date: April 2013

Study information

• Verified date: January 2016
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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, by stopping them from dividing, or by stopping them from spreading. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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/uL

• Platelets > 100,000/uL

• 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)

• Patient is not pregnant; 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

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Adenosquamous
• Carcinoma, Squamous Cell
• Cervical Adenocarcinoma
• Cervical Adenosquamous Carcinoma
• Cervical Squamous Cell Carcinoma
• Stage IB2 Cervical Cancer
• Stage II Vaginal Cancer
• Stage IIA1 Cervical Cancer
• Stage IIA2 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
• Uterine Cervical Neoplasms
• Vaginal Adenocarcinoma
• Vaginal Adenosquamous Carcinoma
• Vaginal Neoplasms
• Vaginal Squamous Cell Carcinoma

Intervention

Drug:
• Cisplatin
Given IV

Radiation:
• External Beam Radiation Therapy
Undergo EBRT
• Internal Radiation Therapy
Undergo HDR or LDR brachytherapy

Other:
• Laboratory Biomarker Analysis
Optional correlative studies

Drug:
• Triapine
Given IV

Locations

Country	Name	City	State
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Northeastern Ohio University College	Rootstown	Ohio
United States	Moffitt Cancer Center	Tampa	Florida

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	18F-FDG PET/CT metabolic complete response by European Organization for Research and Treatment of Cancer criteria		3 months	No
Secondary	Acute (less than 30 day) adverse events, graded according to National Cancer Institute (NCI) CTCAE, version 4		Up to 30 days	Yes
Secondary	Clinical response as measured by RECIST version 1.1		Up to 6 months	No
Secondary	Late (greater than or equal to 30 day) adverse events, graded according to NCI CTCAE v4.0		Up to 6 months	Yes
Secondary	Methemoglobin percentage after triapine infusion (Optional)	Methemoglobin will be reported as a percentage of total hemoglobin.	Up to 24 hours after triapine infusion	No
Secondary	Progression-free survival	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.	The time from start of treatment until time of progression, recurrence, or death, assessed up to 6 months	No