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

Phase 2

Withdrawn

• Conditions: FIGO Stage IVA Cervix Carcinoma; HIV Infection; Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; FIGO Stage IIB Cervix Carcinoma; Cervical Adenosquamous Carcinoma; FIGO Stage III Cervix Carcinoma
• Interventions: Drug: Carboplatin; Procedure: Patient Monitoring; Drug: Cisplatin; Drug: Paclitaxel; Radiation: Radiation Therapy

• Registration Number: NCT03834571
• Lead Sponsor: AIDS Malignancy Consortium

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-02-06
• Study First Submitted QC: 2019-02-06
• Study First Posted: 2019-02-08
• Study Start: 2022-05-31
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-14
• Last Update Posted: 2022-06-21
• Primary Completion: 2025-01
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (standard care, carboplatin, paclitaxel)	Radiation Therapy	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.
Arm II (standard care, active monitoring)	Patient 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.
Arm II (standard care, active monitoring)	Radiation Therapy	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.
Arm I (standard care, carboplatin, paclitaxel)	Carboplatin	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.
Arm I (standard care, carboplatin, paclitaxel)	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.
Arm I (standard care, carboplatin, paclitaxel)	Cisplatin	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.
Arm II (standard care, active monitoring)	Cisplatin	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.

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) evaluated using Response Evaluation Criteria in Solid Tumors 1.1	The time from registration enrollment to disease recurrence, disease progression, or death for any reason, assessed up to 2 years	The intervention arm will be compared to the control arm for improvement in PFS via one-sided log-rank test. This test will be conducted once for the interim analysis and once for the final analysis.

Secondary Outcome Measures

Name	Time	Method
Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Up to 2 years	The frequency of adverse events (AEs) and their severity will be tabulated to evaluate the safety and tolerability. Safety and tolerability will be evaluated through tracking the number of dose delays, dose reductions, missing doses, and number of doses received and compliance.
Progression free survival by stage	Up to 2 years	The Kaplan Meier method will be used to estimate the 2-year PFS and corresponding 95% confidence intervals of human immunodeficiency virus (HIV)-infected women with locally advanced cervical cancer (LACC) treated on study, stratified by FIGO 2018 stage.
Treatment effect on participants HIV disease status by assessing CD4 counts	Up to 2 years	Descriptive statistics will be used to describe the effects of treatment on participants' HIV disease status by assessing CD4 counts.
Progression free survival (PFS) in women not meeting criteria for randomization by stage	Up to 2 years	The Kaplan Meier method will be used to estimate the 2-year PFS and corresponding 95% confidence intervals of HIV-infected women with LACC treated on study but who did not meet the eligibility criteria for randomization, stratified by FIGO 2018 stage.
Treatment effect on HIV disease status by assessing HIV viral load	Up to 2 years	Descriptive statistics will be used to describe the effects of treatment on participants' HIV disease status by assessing HIV viral load.
Cervical cancer recurrence patterns	Up to 2 years	Binomial proportions and their corresponding 95% confidence intervals will be used to describe cervical cancer recurrence patterns in HIV-infected participants with LACC defined as loco-regional and/or distant recurrences.
Overall survival (OS)	From entry to protocol to death; or for living participants, the date of last contact, assessed up to 2 years	The Kaplan Meier method and corresponding 95% confidence interval will be used to estimate the overall survival. The causes of death will be listed.

Trial Locations

Locations (3)

Parirenyatwa Hospital; 🇿🇼 Harare, Zimbabwe

Stellenbosch University; 🇿🇦 Cape Town, South Africa

University of Witwatersrand; 🇿🇦 Johannesburg, South Africa