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

NCT03834571 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: AMC-102NCI-2018-01903UM1CA121947
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 3

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.

Conditions

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

Keywords

Cervical Cancer; HIV Infection

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) evaluated using Response Evaluation Criteria in Solid Tumors 1.1

  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.

  The time from registration enrollment to disease recurrence, disease progression, or death for any reason, assessed up to 2 years

Secondary Outcomes (7)

• Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  Up to 2 years

• Progression free survival by stage

  Up to 2 years

• Treatment effect on participants HIV disease status by assessing CD4 counts

  Up to 2 years

• Treatment effect on HIV disease status by assessing HIV viral load

  Up to 2 years

• Cervical cancer recurrence patterns

  Up to 2 years

Other Outcomes (5)

• Evaluation of cervical human papilloma virus (HPV) types

  Up to 2 years

• Persistence of cervical HPV pre-treatment

  Up to 2 years

• Persistence of cervical HPV post-treatment

  Up to 2 years

Study Arms (2)

Arm I (standard care, carboplatin, paclitaxel)

EXPERIMENTAL

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.

Drug: Carboplatin; Drug: Cisplatin; Drug: Paclitaxel; Radiation: Radiation Therapy

Arm II (standard care, active monitoring)

ACTIVE COMPARATOR

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.

Drug: Cisplatin; Procedure: Patient Monitoring; Radiation: Radiation Therapy

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm I (standard care, carboplatin, paclitaxel)

Cisplatin DRUG

Given IV

Also known as: 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

Arm I (standard care, carboplatin, paclitaxel); Arm II (standard care, active monitoring)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm I (standard care, carboplatin, paclitaxel)

Patient Monitoring PROCEDURE

Undergo active monitoring

Also known as: monitor

Arm II (standard care, active monitoring)

Radiation Therapy RADIATION

Undergo radiation

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, Radiation, Radiotherapeutics, RADIOTHERAPY, RT, Therapy, Radiation

Arm I (standard care, carboplatin, paclitaxel); Arm II (standard care, active monitoring)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• AIDS Malignancy Consortium: lead
• National Cancer Institute (NCI): collaborator
• The Emmes Company, LLC: collaborator
• University of Stellenbosch: collaborator
• University of Arkansas: collaborator

Study Sites (3)

Stellenbosch University

Cape Town, South Africa

Location

University of Witwatersrand

Johannesburg, South Africa

Location

Parirenyatwa Hospital

Harare, Zimbabwe

Location

MeSH Terms

Conditions

HIV Infections; Uterine Cervical Neoplasms

Interventions

Carboplatin; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Paclitaxel; Taxes; Remote Patient Monitoring; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Telemedicine; Delivery of Health Care; Patient Care Management; Health Services Administration; Therapeutics; Physical Phenomena

Study Officials

• Ntokozo Ndlovu

  Parirenyatwa Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 6, 2019
• First Posted: February 8, 2019
• Study Start: May 31, 2022
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: June 21, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (2); ZI (1)