Trials / Completed

CompletedNCT03738228

Atezolizumab Before and/or With Chemoradiotherapy in Immune System Activation in Patients With Node Positive Stage IB2, II, IIIB, or IVA Cervical Cancer

Anti PD-L1 (Atezolizumab) as an Immune Primer and Concurrently With Extended Field Chemoradiotherapy for Node Positive Locally Advanced Cervical Cancer

Status: Completed
Phase: Phase 1
Study type: Interventional
Enrollment: 40 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: Female
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I trial studies how well atezolizumab before and/or with standard of care chemoradiotherapy works in immune system activation in patients with stage IB2, II, IIIB, or IVA cervical cancer that has spread to the lymph nodes. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab before and/or with chemoradiotherapy may lower the chance of tumors growing or spreading.

Detailed description

PRIMARY OBJECTIVES: I. To determine whether differences in sequencing of atezolizumab and chemoradiation result in differential immune activation, as determined by clonal expansion of T cell receptor beta (TCRB) repertoires in peripheral blood on day 21. SECONDARY OBJECTIVES: I. To investigate the feasibility of administration of the anti PD-L1 antibody (atezolizumab) as an immune primer and concurrent with chemoradiation (CRT) therapy in patients with locally advanced cervical cancer. II. To determine the nature and degree of toxicity of the anti PD-L1 antibody (atezolizumab) administered as an immune primer and concurrent with chemoradiation (CRT) therapy in patients with locally advanced cervical cancer. III. To examine the changes in T cell receptor (TCR) clonality, diversity, and frequency in peripheral blood and tissue and correlate this with clinical outcomes, such as the exploratory response assessment on the post-treatment positron emission tomography (PET)-computed tomography (CT) scan and 2-year disease-free survival (DFS). IV. To assess the predictive value of baseline and on-treatment PD-L1 expression in the tissue in each treatment arm for clinical outcomes using post-treatment PET-CT scan and 2-year DFS as the outcome measures. EXPLORATORY OBJECTIVES: I. To explore baseline and on-treatment blood and tissue biomarkers that could predict response to the combination therapy, as correlated to the exploratory clinical endpoint of the week 12 (day 140) PET-CT scan and 2-year DFS. II. To explore the response assessment on the exploratory and optional post-treatment week 12 (day 140) PET-CT scan and the clinical 2-year disease free survival (DFS). OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on days -21, 0, and 21 in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care cisplatin chemotherapy IV over 90 minutes on days 0, 7, 14, 21, 28, and 35. Beginning on day 0, patients also receive standard of care radiation therapy once daily (Monday-Friday) for a total of 25 fractions with image guided brachytherapy beginning in week 4, 5, or at the end of radiation therapy. ARM B: Patients receive atezolizumab IV over 30-60 minutes on days 0, 21, and 42 in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care cisplatin chemotherapy, radiation therapy, and image guided brachytherapy as in Arm A. After completion of study treatment, patients are followed up at 1 and 3 months, and then every 3 months for 2 years.

Conditions

Interventions

Type	Name	Description
DRUG	Atezolizumab	Given IV
RADIATION	Brachytherapy	Undergo standard of care image guided brachytherapy
DRUG	Cisplatin	Given IV
RADIATION	Radiation Therapy	Undergo standard of care radiation therapy

Timeline

Start date: 2019-01-07
Primary completion: 2022-05-01
Completion: 2025-09-12
First posted: 2018-11-13
Last updated: 2025-11-12
Results posted: 2023-07-20

Locations

16 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT03738228. Inclusion in this directory is not an endorsement.