Cisplatin and Radiation Therapy in Treating Patients With HIV-Associated Locally Advanced Cervical Cancer

NCT ID: NCT01590017

Last Updated: 2022-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-01
• Study Completion Date: 2017-04-20

Brief Summary

RATIONALE: 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 cisplatin together with radiation therapy may be an effective treatment for cervical cancer.

PURPOSE: This trial studies how well cisplatin and radiation therapy work in treating participants with HIV-associated locally advanced cervical cancer.

Detailed Description

OBJECTIVES:

Primary

• To determine if it is feasible to administer a regimen of cisplatin/radiotherapy in HIV-infected women with locally advanced cervical cancer (LACC) on antiretroviral therapy (ART).
• To evaluate the safety and tolerability of concomitant chemoradiotherapy with cisplatin in HIV-infected women with LACC who are also receiving concomitant ART.

Secondary

• To determine the 1-year progression-free survival (PFS) of HIV-infected women with LACC Stage IB, II, III, or IVA who receive weekly cisplatin concomitant with radiotherapy and ART. (Exploratory)
• To describe the quality of life (QOL) of enrolled participants via assessments before, immediately after, and at 3 and 9 months after completion of therapy, using QOL metrics that have been validated in similar populations. (Exploratory)
• To describe the effects of treatment on participants' CD4 counts, HIV viral load, and concurrent AIDS-defining conditions. (Exploratory)
• To describe cervical cancer recurrence patterns in HIV-infected participants with LACC defined as loco-regional and/or distant recurrences. (Exploratory)
• To determine 1-year overall survival and causes of death (i.e., cancer-related, HIV-related, or other). (Exploratory)
• To collect serum, cytology, and tissue for future studies specific to cervical and anal disease. (Exploratory)
• To evaluate the effects of weekly cisplatin concomitant with radiotherapy on adherence to ART. (Exploratory)

OUTLINE: This is a multicenter study.

Participants receive cisplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36 (6 weeks total). Participants also undergo whole pelvic radiotherapy (WPRT) 5 days a week for 5 weeks followed by intracavitary brachytherapy.

Participants complete the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-30 and the Cervical Cancer Module (QLQ-CX24) at baseline and periodically during study treatment.

After completion of study treatment, participants are followed up every 3 months for 12 months.

Conditions

Cervical Cancer; Acquired Immunodeficiency Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cistplatin and Radiation Therapy

Cisplatin 40 mg/m2 (max = 70 mg) IV over 30-60 minutes given weekly on days 1, 8, 15, 22, 29 and 36 for a total of 6 weekly cycles. Radiation therapy over 8 weeks: External pelvic radiation therapy (41.4-45.0 Gy/1.8 Gy per fraction/23-25 fractions/five weeks), intracavitary brachytherapy (low dose: 35-43.6 Gy/1-2 implants; high dose: 18-28 Gy/2-4 implants), with parametrial boost to involved parametria (5.40 - 9.00 Gy/1.8 Gy/3-5 fractions/3-5 days).

Group Type: EXPERIMENTAL

cisplatin

Intervention Type: DRUG

external beam radiation therapy

Intervention Type: RADIATION

Interventions

cisplatin

Intervention Type: DRUG

external beam radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Creatinine clearance ≥ 60 mL/min (1.00 mL/s) calculated by the Cockcroft-Gault equation for women
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times upper limit of normal (ULN)
• Total bilirubin ≤ 2 times ULN unless related to antiretroviral use (e.g., atazanavir and indinavir), then the direct bilirubin must be ≤ 2 times ULN
• Ability to understand and the willingness to provide informed consent to participate
• Karnofsky performance status of ≥ 60%
• Participants of childbearing potential, defined as a sexually mature woman who has not undergone a hysterectomy or bilateral oophorectomy or has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months), must have a negative urine or serum pregnancy test within 3 weeks prior to enrollment and agree to use an effective form of contraception (e.g., barrier contraception, highly effective hormonal contraception)
• Life expectancy of greater than 12 months
• No acute active (such as tuberculosis or malaria), serious, uncontrolled infection; participants with a CD4 count < 50/mm³ (0.05 x 10^9/L) will be excluded if they have had an opportunistic infection within the past 3 months, or if there is evidence of resistance to antiretroviral therapy (i.e., HIV viral load ≥ 400 copies/mL despite combination antiretroviral therapy for at least 4 months)
• No prior invasive malignancy other than LACC diagnosed within the past 24 months, excluding anal intraepithelial neoplasia, non-melanoma skin carcinoma, or Kaposi sarcoma that has not required systemic chemotherapy within the past 24 months
• No pregnancy or breast-feeding
• No medical or psychiatric illness that precludes ability to give informed consent or is likely to interfere with the ability to comply with the protocol stipulations
• No participants with circumstances that will not permit completion of the study or required follow-up; for instance, if travel to and from treatment site is an issue
• No participants with cardiovascular disease manifested as:

• History of myocardial infarction
• Unstable angina
• Currently taking medication for treatment of angina
• History of coronary artery bypass surgery
• New York Heart Association class 3 or 4 heart failure

PRIOR CONCURRENT THERAPY:

• See Patient Characteristics
• All patients must be prescribed combination antiretroviral therapy with the goal of virological suppression using an acceptable regimen that adheres to national guidelines for treatment of HIV infection

• Non-suppressed, treatment-experienced patients, defined as patients with a viral load > 400 copies/mL who have been on antiretroviral therapy for more than 4 months, can be enrolled if a genotype assay is performed and an acceptable regimen is prescribed based on the genotyping results
• Patients who undergo emergency radiation therapy prior to enrollment may participate at the investigator's discretion
• No participants who have undergone hysterectomy
• No concurrent intensity-modulated radiotherapy or interstitial brachytherapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

The Emmes Company, LLC

INDUSTRY

Sponsor Role: collaborator

University of Arkansas

OTHER

Sponsor Role: collaborator

Montefiore Medical Center

OTHER

Sponsor Role: collaborator

AIDS Malignancy Consortium

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark H. Einstein, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Albert Einstein College of Medicine

Locations

Clinical HIV Research Unit, a Division of the Wits Health Consortium (Pty) Ltd

Johannesburg, , South Africa

University of Zimbabwe Clinical Research Centre / Parirenyatwa Hospital

Harare, , Zimbabwe

Countries

South Africa; Zimbabwe

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CDR0000732629

Identifier Type: OTHER

Identifier Source: secondary_id

UM1CA121947

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AMC-081

Identifier Type: -

Identifier Source: org_study_id