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Induction Pembrolizumab and Chemotherapy Followed by Pembrolizumab Before Chemoradiation and Pembrolizumab Maintenance Compared to Standard Chemoradiation With Pembrolizumab Followed by Pembrolizumab Maintenance in High-Risk Cervical Cancer

ConditionsLocally Advanced Cervical AdenocarcinomaLocally Advanced Cervical Adenosquamous CarcinomaLocally Advanced Cervical Squamous Cell CarcinomaStage IIIA Cervical Cancer FIGO 2018Stage IIIB Cervical Cancer FIGO 2018Stage IIIC1 Cervical Cancer FIGO 2018Stage IIIC2 Cervical Cancer FIGO 2018Stage IVA Cervical Cancer FIGO 2018
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexFemale
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

This phase III trial compares the addition of induction chemotherapy, with carboplatin, paclitaxel and pembrolizumab, to chemotherapy and radiation, with cisplatin and pembrolizumab followed by pembrolizumab maintenance for the treatment of patients with cervical cancer that has spread to nearby tissue or lymph nodes (locally advanced). Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Adding induction chemotherapy to the usual treatment of chemotherapy and radiation followed by maintenance may be more effective in treating patients with high risk, locally advanced cervical cancer.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients must have pathologically confirmed newly diagnosed cervical cancer. Eligible pathologic types: squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma

IIIA (T3aN0M0)

IIIB (T3bN0M0)

IIIC1(T3aN1M0, T3bN1M0)

Disqualifiers

None

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Brachytherapy

    Radiation

    Undergo brachytherapy

  • Carboplatin

    Drug

    Given IV

  • Chest Radiography

    Procedure/Surgery

    Undergo chest x-ray

  • Cisplatin

    Drug

    Given IV

  • Computed Tomography

    Procedure/Surgery

    Undergo CT scan

  • External Beam Radiation Therapy

    Radiation

    Undergo EBRT

  • Intensity-Modulated Radiation Therapy

    Radiation

    Undergo IMRT

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Paclitaxel

    Drug

    Given IV

  • Pembrolizumab

    Biological/Vaccine

    Given IV

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET scan

Treatment groups

336 Participants
are divided into 2 treatment groups
Group A: Arm 1 (Standard care)Active comparator 10 interventions
Group B: Arm 2 (induction and standard care)Experimental treatment 12 interventions

Trial outcomes

Primary outcomes

1

Progression free survival (PFS)

Analysis will be performed using a one-sided log-rank test stratified by factors declared at randomization when (at least) 190 PFS events are observed in both arms. Patients will be grouped by their randomized treatment for intention-to-treat (ITT) analyses, supported by patients in ITT population. Treatment hazard ratio and confidence will be estimated using Cox proportional hazard models specified with a main effect for the randomized treatment assignment and stratified by factors declared at randomization. PFS at 2 years will be estimated using Kaplan-Meier method for each arm.

Time frame
From randomization to time of progression or death from any cause, whichever occurs first, or date of last contact if neither progression nor death has occurred, up to 7 years

Secondary outcomes

1

Overall survival (OS)

The OS treatment hypothesis test (Arm 2 versus \[vs.\] Arm 1) will be based on a 1-sided log-rank test, stratified by the factors specified at randomization. Comparisons of the OS distributions by treatment arm will be described using Kaplan-Meier methods. Treatment hazard ratio estimates and their 95% confidence intervals will be estimated using a multivariable proportional hazards model specified with main effects for the randomized treatment assignment (Arm 2 vs Arm 1) and stratified by the factors declared at randomization.

Time frame
From randomization to death from any cause, up to 7 years
2

Incidence of adverse events (AEs)

Assessed by Common Terminology Criteria for Adverse Events version 5.0. The nature, frequency, and degree of toxicity will be tabulated at the System Organ Class and AE-specific term levels. Tabulations will show the number and percentage of patients by maximum grade, within the treatment group received, regardless of the randomized treatment assignment. Differences in the level of toxicities by treatment arm will be assessed by classifying them as severe (grade 3 or higher) or not severe (grade 2 or lower) and examining the relative proportion of severe toxicities by Fisher's exact test.

Time frame
Up to 7 years
3

Duration of concurrent chemoradiation therapy (CCRT) completion

Will be summarized and compared using 2-sample Wilcoxon rank sum tests. The proportion of patients with a delayed time to initiate CCRT by 2 weeks or more will be estimated and investigated by Fisher's exact test.

Time frame
From CCRT start date to CCRT end date
4

Number of cycles of cisplatin

Will be summarized and compared using 2-sample Wilcoxon rank sum tests.

Time frame
From 7 days after the last dose of induction chemotherapy to the CCRT start date for Arm 2, the planned CCRT start date to actual CCRT start date for Arm 1

Other outcomes

1

T cell receptor (TCR) expression

Will be summarized by treatment arm, and its correlation with PFS/OS will be investigated using Cox PH model adjusted with main effects for the randomized treatment assignment (Arm 2 vs Arm 1) and stratified by the factors declared at randomization. Repeated measure methods (e.g., linear mixed model) will be used for exploration of TCR evolution/trajectory on treatment.

Time frame
Up to 7 years
2

Tumor microenvironment

The predictive values of each of the pre-treatment tumor microenvironment biomarkers for PFS and OS will be investigated using Cox PH model adjusted with main effects for the randomized treatment assignment (Arm 2 vs Arm 1) and stratified by the factors declared at randomization.

Time frame
At baseline

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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