Testing the Addition of Paclitaxel and Carboplatin Given After Standard Chemotherapy and Radiation for Cervical Cancer in HIV-positive Women

NCT ID: NCT03834571

Last Updated: 2022-06-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-31

Study Completion Date

2025-01-31

Brief Summary

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This phase II trial studies how well standard chemotherapy and radiation therapy given with or without paclitaxel and carboplatin work in treating human immunodeficiency virus (HIV)-positive women with cervical cancer that has spread to nearby tissue or lymph nodes. Drugs used in chemotherapy, such as cisplatin, paclitaxel, and carboplatin work in different ways to stop the growth of tumor cells. They may either kill the cancer cells by stopping them from dividing, or by stopping them from spreading. Radiation therapy to the pelvis destroys potential cancer cells in the pelvic area and significantly reduces the risk of tumor recurrence in the pelvic area. It is not yet known if giving chemotherapy and radiation therapy with paclitaxel and carboplatin afterward may work better than than just chemotherapy and radiation therapy in treating HIV-positive patients with advanced cervical cancer.

Detailed Description

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STANDARD CARE: All participants receive cisplatin intravenously (IV) over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Patients also undergo radiation therapy over 2-5 fractions for 5 days a week, for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Four (4) to 8 weeks after finishing standard chemotherapy and radiation, participants are randomized to 1 of 2 arms.

RANDOMIZED ARMS:

Arm I: Patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1. Courses repeat every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Participants are followed at 3, 6, 9, 12, 18 and 24 months for recurrence or progression.

Arm II: Participants undergo active monitoring at 3, 6, 9, 12, 18 and 24 months for recurrence or progression.

Conditions

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Cervical Adenocarcinoma Cervical Adenosquamous Carcinoma Cervical Squamous Cell Carcinoma, Not Otherwise Specified FIGO Stage IIB Cervix Carcinoma FIGO Stage III Cervix Carcinoma FIGO Stage IVA Cervix Carcinoma HIV Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

All participants will receive standard chemotherapy and radiation for the first 8 weeks of the trial. Four (4) to 8 weeks after finishing standard therapy, participants meeting eligibility criteria for randomization will be assigned to 1 of 2 arms. Arm 1 will receive up to 4 cycles of adjuvant IV chemotherapy (carboplatin and paclitaxel, 21-day cycle length), and arm 2 will undergo active monitoring for cancer recurrence or progression. All participants will be monitored every 3 months for recurrence or progression through 2 years after study enrollment.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I (standard care, carboplatin, paclitaxel)

STANDARD CARE: Patients receive cisplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Patients also undergo radiation therapy over 2-5 fractions 5 days a week for up to 8 weeks in the absence if disease progression or unacceptable toxicity. 4-8 weeks following standard of care.

4-8 weeks following standard care, patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1. Courses repeat every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Carboplatin

Intervention Type DRUG

Given IV

Cisplatin

Intervention Type DRUG

Given IV

Paclitaxel

Intervention Type DRUG

Given IV

Radiation Therapy

Intervention Type RADIATION

Undergo radiation

Arm II (standard care, active monitoring)

STANDARD CARE: Patients receive cisplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Patients also undergo radiation therapy over 2-5 fractions 5 days a week for up to 8 weeks in the absence if disease progression or unacceptable toxicity. 4-8 weeks following standard of care.

4-8 weeks following standard care, patients undergo active monitoring at 3, 6, 9, 12, 18 and 24 months.

Group Type ACTIVE_COMPARATOR

Cisplatin

Intervention Type DRUG

Given IV

Patient Monitoring

Intervention Type PROCEDURE

Undergo active monitoring

Radiation Therapy

Intervention Type RADIATION

Undergo radiation

Interventions

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Carboplatin

Given IV

Intervention Type DRUG

Cisplatin

Given IV

Intervention Type DRUG

Paclitaxel

Given IV

Intervention Type DRUG

Patient Monitoring

Undergo active monitoring

Intervention Type PROCEDURE

Radiation Therapy

Undergo radiation

Intervention Type RADIATION

Other Intervention Names

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Blastocarb Carboplat Carboplatin Hexal Carboplatino Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum Cis-dichloroammine Platinum (II) Cis-platinous Diamine Dichloride Cis-platinum Cis-platinum II Cis-platinum II Diamine Dichloride Cismaplat Cisplatina Cisplatinum Cisplatyl Citoplatino Citosin Cysplatyna DDP Lederplatin Metaplatin Neoplatin Peyrone's Chloride Peyrone's Salt Placis Plastistil Platamine Platiblastin Platiblastin-S Platinex Platinol Platinol- AQ Platinol-AQ Platinol-AQ VHA Plus Platinoxan Platinum Platinum Diamminodichloride Platiran Platistin Platosin Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat monitor Cancer Radiotherapy Irradiate Irradiated irradiation Radiation Radiotherapeutics RADIOTHERAPY RT Therapy, Radiation

Eligibility Criteria

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Inclusion Criteria

* Participants with locally advanced primary, untreated, histologically-confirmed, documented invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, adequately clinically staged by standard clinical guidelines, with Federation of Gynecology and Obstetrics (FIGO) stages IIB, III, or IVA
* HIV positive. Documentation of HIV-1 infection by means of any one of the following:

* Documentation of receipt of ART by a licensed health care provider (documentation may be a record of an ART prescription in the participant's medical record, a written prescription in the name of the participant for ART, or pill bottles for ART with a label showing the participant's name)
* HIV-1 ribonucleic acid (RNA) detection by a licensed HIV-1 RNA assay demonstrating \>1000 RNA copies/mL confirmed by a licensed screening antibody and/or HIV antibody antigen combination assay
* Any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot confirmation or HIV rapid multispot antibody differentiation assay.

* Note: The term "licensed" refers to a kit that has been certified or licensed by an oversight body within the participating 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.
* Hemoglobin \>= 10 g/dL (6.2 mmol/L) (participants receiving transfusion are permitted) (within 4 weeks prior to enrollment)
* Leukocytes: \>= 3,000/mm\^3 (3.0 x 10\^9/L) (within 4 weeks prior to enrollment)
* Absolute neutrophil count: \>= 1,500/mm\^3 (1.5 x 10\^9/L) (within 4 weeks prior to enrollment)
* Platelets: \>= 100,000/mm\^3 (100 x 10\^9/L) (within 4 weeks prior to enrollment)
* CD4 T-cell count a minimum of 200 cells/uL (within 4 weeks prior to enrollment)
* Total bilirubin =\< 2 x institutional upper limit of normal (ULN) unless related to antiretroviral use (e.g., atazanavir or indinavir), then the direct bilirubin must be =\< 2 x ULN (within 4 weeks prior to enrollment)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]): =\< 3 x ULN (within 4 weeks prior to enrollment)
* Creatinine levels within normal institutional limits or, creatinine clearance \>= 60 mL/min/1.73 m\^2 (1.00 mL/s) calculated by the Cockcroft-Gault equation for women for participants with creatinine levels above institutional normal (within 4 weeks prior to enrollment)
* All participants 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. If on a ritonavir- or cobicistat-based regimen, the participant must be switched to a non-ritonavir/ cobicistat-based regimen at least 7 days before treatment enrollment. Participants not on ART must start an acceptable regimen at least 7 days before treatment enrollment.
* In the investigator's opinion the participant is suitable for treatment with radical intent using concurrent chemotherapy and pelvic radiation followed by adjuvant chemotherapy
* Participants of childbearing potential, defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) 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) for the duration of treatment and for 6 weeks after stopping treatment
* Life expectancy of greater than 6 months

Exclusion Criteria

* Participants who have had chemotherapy for cervical cancer within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
* Participants who are receiving any other investigational agents
* Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicity \> grade 1).
* Participants who have undergone hysterectomy including supracervical hysterectomy
* Acute active (such as tuberculosis or malaria), serious, uncontrolled infection
* Prior invasive malignancy requiring systemic chemotherapy diagnosed within the past 24 months (other than LACC)
* A 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
* 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
* Participants with carcinoma of the cervical stump
* Participants with history of 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
* Participants with enlarged para-aortic lymph node involvement above L3 on imaging that are suspicious for metastasis
* History of allergic reactions attributed to compounds of similar chemical or biological composition to study drugs (cisplatin, carboplatin, and paclitaxel)
* Participants who are breastfeeding a child. Cisplatin is known to be excreted in human milk.

Eligibility for Randomization

* Participants must have organ and marrow function within the following parameters within 4-8 weeks post CDDP/RT to be eligible for randomization
* Absolute neutrophil count: ≥1,500/mm3 (1.5 x 109/L)
* Platelets: ≥ 100,000/mm3 (100 x 109/L)
* CD4 T-cell \> 100 cells/µL
* HIV viral load \< 400 copies/mL
* ECOG performance status ≤ 2 (Karnofsky ≥ 50%).
* Successful completion of CDDP/RT, defined as receiving 4-6 cycles of cisplatin and completion of the equivalent dose per fraction of \>78 Gy to Point A.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

The Emmes Company, LLC

INDUSTRY

Sponsor Role collaborator

University of Stellenbosch

OTHER

Sponsor Role collaborator

University of Arkansas

OTHER

Sponsor Role collaborator

AIDS Malignancy Consortium

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ntokozo Ndlovu

Role: PRINCIPAL_INVESTIGATOR

Parirenyatwa Hospital

Locations

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Stellenbosch University

Cape Town, , South Africa

Site Status

University of Witwatersrand

Johannesburg, , South Africa

Site Status

Parirenyatwa Hospital

Harare, , Zimbabwe

Site Status

Countries

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South Africa Zimbabwe

Other Identifiers

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NCI-2018-01903

Identifier Type: REGISTRY

Identifier Source: secondary_id

AMC-102

Identifier Type: OTHER

Identifier Source: secondary_id

AMC-102

Identifier Type: OTHER

Identifier Source: secondary_id

UM1CA121947

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AMC-102

Identifier Type: -

Identifier Source: org_study_id

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