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Cervical AdenocarcinomaPhase 2NCT03834571

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

A Phase 2 study testing Carboplatin, Cisplatin and Paclitaxel in people with Cervical Adenocarcinoma and Cervical Adenosquamous Carcinoma, run by AIDS Malignancy Consortium at 3 sites in 2 countries.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Carboplatin, Cisplatin and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
3 sitesin 2 countries
Study dates
31 May 2022to Jan 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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)
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  • 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.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

South Africa2 sites

  • Stellenbosch University

    Cape Town

  • University of Witwatersrand

    Johannesburg

Other trials in South Africa

Zimbabwe1 site

  • Parirenyatwa Hospital

    Harare

Other trials in Zimbabwe

About this study

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)

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.

Read the 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.

Being tested
Carboplatin, Cisplatin, Paclitaxel, Patient Monitoring, Radiation Therapy
Keywords
Cervical Cancer, HIV Infection
Medical subject headings
HIV Infections, Uterine Cervical Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • Patient MonitoringProcedure or surgery

    Also called monitor

    Undergo active monitoring

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Irradiate, Irradiated, irradiation

    Undergo radiation

Study groups in NCT03834571
Study groupRoleWhat they receive
Arm I (standard care, carboplatin, paclitaxel)ExperimentalSTANDARD 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.
Receives: Drug: Carboplatin; Drug: Cisplatin; Drug: Paclitaxel; Radiation: Radiation Therapy
Arm II (standard care, active monitoring)Active comparatorSTANDARD 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.
Receives: Drug: Cisplatin; Procedure: Patient Monitoring; Radiation: Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (7)

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

    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.

    Measured: Up to 2 years

  2. Progression free survival by stage

    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.

    Measured: Up to 2 years

  3. Treatment effect on participants HIV disease status by assessing CD4 counts

    Descriptive statistics will be used to describe the effects of treatment on participants' HIV disease status by assessing CD4 counts.

    Measured: Up to 2 years

  4. Treatment effect on HIV disease status by assessing HIV viral load

    Descriptive statistics will be used to describe the effects of treatment on participants' HIV disease status by assessing HIV viral load.

    Measured: Up to 2 years

  5. Cervical cancer recurrence patterns

    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.

    Measured: Up to 2 years

  6. Overall survival (OS)

    The Kaplan Meier method and corresponding 95% confidence interval will be used to estimate the overall survival. The causes of death will be listed.

    Measured: From entry to protocol to death; or for living participants, the date of last contact, assessed up to 2 years

  7. Progression free survival (PFS) in women not meeting criteria for randomization by stage

    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.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2019
  2. Study start31 May 2022 (estimated)
  3. Primary completionJan 2025 (estimated)
  4. Study completionJan 2025 (estimated)

Why it stopped: Not approved by CTEP

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03834571
Sponsor's protocol ID
AMC-102
Other IDs
NCI-2018-01903, AMC-102, AMC-102, UM1CA121947
Status last verified
Jun 2022
First submitted
6 Feb 2019
Last updated
21 Jun 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carboplatin, Cisplatin and Paclitaxel in people with Cervical Adenocarcinoma and Cervical Adenosquamous Carcinoma, run by AIDS Malignancy Consortium at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 21 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in South Africa, Zimbabwe. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03834571.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2022.

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