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Trial record 2 of 8 for:    "Cervical Adenocarcinoma" | "Carboplatin"

Standard Chemotherapy and Radiation Therapy With or Without Paclitaxel and Carboplatin in Treating HIV-Positive Women With Locally Advanced Cervical Cancer

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ClinicalTrials.gov Identifier: NCT03834571
Recruitment Status : Not yet recruiting
First Posted : February 8, 2019
Last Update Posted : February 8, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
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, either by killing the 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 or without paclitaxel and carboplatin, may work better in treating HIV-positive patients with advanced cervical cancer.

Condition or disease Intervention/treatment Phase
Cervical Adenocarcinoma Cervical Adenosquamous Carcinoma Cervical Squamous Cell Carcinoma, Not Otherwise Specified FIGO Stage IIB FIGO Stage IIIA FIGO Stage IIIB FIGO Stage IVA HIV Infection Drug: Carboplatin Drug: Cisplatin Drug: Paclitaxel Procedure: Patient Monitoring Radiation: Radiation Therapy Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the efficacy, as defined as 2-year progression-free survival (PFS), of concomitant chemoradiotherapy (CDDP/RT) and antiretroviral therapy (ART) with or without adjuvant therapy in HIV-positive women with locally advanced cervical cancer (LACC) Stage IIB, III, and IVA.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of concomitant CDDP/RT with or without adjuvant chemotherapy in HIV-positive women (on ART) with LACC.

II. To estimate the 2-year PFS of HIV-positive women with LACC treated on study, stratified by stage and nodal status.

III. To estimate the effects of treatment on the participant's HIV disease status by assessing HIV viral load and CD4 counts post completion of cancer therapy.

IV. To describe the cervical cancer recurrence patterns in HIV-positive participants with LACC defined as loco-regional and/or distant recurrences.

V. Determine 2-year overall survival and causes of death (i.e., cancer-related, HIV-related, or other).

VI. To estimate the 2-year PFS of HIV-positive women with LACC treated on study but who did not meet eligibility criteria for randomization, stratified by 1) stage and 2) nodal status.

EXPLORATORY OBJECTIVES:

I. Evaluate the cervical human papillomavirus (HPV) types present in HIV-positive women with cervical cancer.

II. Assess persistence of cervical HPV pre- and post-treatment. III. Assess the presence of HPV in the anus pre- and post-treatment.

OUTLINE:

STANDARD CARE: Patients 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 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, patients are randomized to 1 of 2 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.

Arm II: Patients undergo active monitoring at 3, 6, 9, 12, 18 and 24 months.

After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18 and 24 months.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Concurrent Chemotherapy and Pelvic Radiation Therapy With or Without Paclitaxel and Carboplatin in HIV-Positive Women With Locally Advanced Cervical Cancer (LACC)
Estimated Study Start Date : March 1, 2019
Estimated Primary Completion Date : January 31, 2024
Estimated Study Completion Date : January 31, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Cisplatin
Given IV
Other Names:
  • 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

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Radiation: Radiation Therapy
Undergo radiation
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • irradiation
  • Radiation
  • Radiotherapeutics
  • RADIOTHERAPY
  • RT
  • Therapy, Radiation

Active Comparator: 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.

Drug: Cisplatin
Given IV
Other Names:
  • 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

Procedure: Patient Monitoring
Undergo active monitoring
Other Name: monitor

Radiation: Radiation Therapy
Undergo radiation
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • irradiation
  • Radiation
  • Radiotherapeutics
  • RADIOTHERAPY
  • RT
  • Therapy, Radiation




Primary Outcome Measures :
  1. Progression-free survival (PFS) evaluated using Response Evaluation Criteria in Solid Tumors 1.1 [ Time Frame: 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 :
  1. Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: 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.

  2. Progression free survival by stage [ Time Frame: 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 stage.

  3. Progression free survival by nodal status [ Time Frame: 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 nodal status.

  4. Treatment effect on CD4 counts [ Time Frame: Up to 2 years ]
    Descriptive statistics will be used to describe the effects of treatment on participants' CD4 counts.

  5. Treatment effect on HIV viral load [ Time Frame: Up to 2 years ]
    Descriptive statistics will be used to describe the effects of treatment on participants' HIV viral load.

  6. Cervical cancer recurrence patterns [ Time Frame: 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.

  7. Overall survival (OS) [ Time Frame: 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.

  8. Progression free survival (PFS) in women not meeting criteria for randomization by stage [ Time Frame: 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 stage.

  9. Progression free survival (PFS) in women not meeting criteria for randomization by nodal status [ Time Frame: 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 nodal status.


Other Outcome Measures:
  1. Evaluation of cervical human papilloma virus (HPV) types [ Time Frame: Up to 2 years ]
    Counts and binomial proportions will be used to evaluate the cervical HPV types present in the HIV-positive women with cervical cancer.

  2. Persistence of cervical HPV pre-treatment [ Time Frame: Up to 2 years ]
    McNemar's test will be used to assess persistence of cervical HPV pre-treatment.

  3. Persistence of cervical HPV post-treatment [ Time Frame: Up to 2 years ]
    McNemar's test will be used to assess persistence of cervical HPV post-treatment.

  4. Presence of HPV in the anus pre-treatment [ Time Frame: Up to 2 years ]
    McNemar's test will be used to assess the presence of HPV in the anus pre-treatment.

  5. Presence of HPV in the anus post-treatment [ Time Frame: Up to 2 years ]
    McNemar's test will be used to assess the presence of HPV in the anus post-treatment.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

ELIGIBILITY FOR STUDY ENROLLMENT:

  • Participants with 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, IIIA, IIIB, or IVA

    • Following clinical staging, nodal status will be confirmed by one of the following: 1) computerized tomography (CT) scan (node size greater than or equal to 15 mm short axis diameter) or positron emission tomography (PET)/CT avid (if available at site), 2) fine needle biopsy, 3) extra peritoneal biopsy, or 4) laparoscopic biopsy as per local standard clinical procedures in women with LACC. HIV-positive women with LACC with or without positive pelvic and/or low para-aortic lymph nodes (L3 and below) are eligible for the trial
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%)
  • 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, it is recommended the participant be switched to a non-ritonavir/ cobicistat-based regimen
  • 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
  • Ability to understand and the willingness to provide informed consent
  • Life expectancy of greater than 6 months

ELIGIBILITY FOR RANDOMIZATION

  • Absolute neutrophil count: >= 1,500/mm^3 (1.5 x 10^9/L) (within 4-8 weeks post CDDP/RT)
  • Platelets: >= 100,000/mm^3 (100 x 10^9/L) (within 4-8 weeks post CDDP/RT)
  • CD4 T-cell > 100 cells/uL (within 4-8 weeks post CDDP/RT)
  • HIV viral load < 400 copies (within 4-8 weeks post CDDP/RT)
  • ECOG performance status =< 2 (Karnofsky >= 50%)

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03834571


Contacts
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Contact: Ntokozo Ndlovu, MBChB, MMed 263-4-731000 ext 2264 ntokozosgo@gmail.com

Locations
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South Africa
Stellenbosch University Not yet recruiting
Cape Town, South Africa
Contact: Hannah Simonds    +27219384727    hsimonds@sun.ac.za   
Principal Investigator: Hannah Simonds, MBChB MRCP FRCR         
University of Witwatersrand Not yet recruiting
Johannesburg, South Africa
Contact: Vinay Sharma    +27724717644    vinay.sharma@wits.ac.za   
Principal Investigator: Mariza Tunmer, MBChB         
Zimbabwe
Parirenyatwa Hospital Not yet recruiting
Harare, Zimbabwe
Principal Investigator: Ntokozo Ndlovu, MBChB, MMed         
Sponsors and Collaborators
AIDS Malignancy Consortium
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Ntokozo Ndlovu Parirenyatwa Hospital

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Responsible Party: AIDS Malignancy Consortium
ClinicalTrials.gov Identifier: NCT03834571     History of Changes
Other Study ID Numbers: AMC-102
NCI-2018-01903 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AMC-102 ( Other Identifier: AIDS Malignancy Consortium )
AMC-102 ( Other Identifier: CTEP )
UM1CA121947 ( U.S. NIH Grant/Contract )
First Posted: February 8, 2019    Key Record Dates
Last Update Posted: February 8, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
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Carboplatin
Carcinoma
Carcinoma, Squamous Cell
Adenocarcinoma
HIV Infections
Uterine Cervical Neoplasms
Carcinoma, Adenosquamous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Neoplasms, Complex and Mixed
Paclitaxel
Albumin-Bound Paclitaxel
Cisplatin