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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by AIDS Malignancy Clinical Trials Consortium
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier:
NCT01590017
First received: May 1, 2012
Last updated: April 15, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Cervical Cancer
Acquired Immunodeficiency Syndrome
Drug: cisplatin
Radiation: external beam radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Feasibility Study of Safety, Toxicity, and Compliance of Concomitant Chemoradiotherapy for HIV-Associated Locally-Advanced Cervical Cancer

Resource links provided by NLM:


Further study details as provided by AIDS Malignancy Clinical Trials Consortium:

Primary Outcome Measures:
  • Treatment completion rate using the binomial proportion and its 95% confidence interval [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Adverse events as graded by the National Cancer Institute Common Terminology Criteria (CTC) version 4.0 will be tabulated [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 45
Study Start Date: April 2014
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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).
Drug: cisplatin Radiation: external beam radiation therapy

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.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Participants (who have been adequately clinically staged by standard clinical guidelines) with primary, untreated, histologically confirmed, documented invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, stages IB2, IIA, IIB, IIIA, IIIB, and IVA (Stage IIA tumors must be greater than 4 cm)
  • HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 ribonucleic acid (RNA) viral load

    • NOTE: the term "licensed" refers to a United States (U.S) Food and Drug Administration (FDA)-approved kit or for sites located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country and validated internally
    • WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment; a reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a western blot or a plasma HIV-1 RNA viral load
  • No participants with carcinoma of the cervical stump

PATIENT CHARACTERISTICS:

  • Hemoglobin ≥ 10 g/dL (6.2 mmol/L)
  • Platelet count ≥ 100,000/mm³ (100 x 10^9/L)
  • Absolute neutrophil count (ANC) ≥ 1000/mm³ (1.0 x 10^9/L) (participants receiving transfusion, erythropoietin, or myeloid growth factor support will be eligible for this study)
  • 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
  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: NCT01590017

Locations
South Africa
Clinical HIV Research Unit, a Division of the Wits Health Consortium (Pty) Ltd Recruiting
Johannesburg, South Africa, 2092
Contact: J A Kotzen, MD    +27 11 481 2129    jkotzen@yahoo.com   
Principal Investigator: J A Kotzen, MD         
Sponsors and Collaborators
AIDS Malignancy Clinical Trials Consortium
Investigators
Principal Investigator: Mark H. Einstein, MD, MS Albert Einstein College of Medicine of Yeshiva University
  More Information

Additional Information:
No publications provided

Responsible Party: AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier: NCT01590017     History of Changes
Other Study ID Numbers: CDR0000732629, AMC-081, U01CA121947
Study First Received: May 1, 2012
Last Updated: April 15, 2014
Health Authority: Kenya: Institutional Review Board
Kenya: Ministry of Health
South Africa: Human Research Ethics Committee
South Africa: Medicines Control Council
Uganda: National Council for Science and Technology
Uganda: National Drug Authority
Uganda: Research Ethics Committee
United States: Federal Government
United States: Institutional Review Board
Zimbabwe: Medical Research Council

Keywords provided by AIDS Malignancy Clinical Trials Consortium:
stage IB cervical cancer
stage IIA cervical cancer
stage IIB cervical cancer
stage III cervical cancer
stage IVA cervical cancer
cervical adenocarcinoma
cervical adenosquamous cell carcinoma
cervical squamous cell carcinoma
HIV infection

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Uterine Cervical Neoplasms
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 27, 2014