GA NCORP

NCORP Trials

Testing the Addition of the Pill Chemotherapy, Cabozantinib, to the Standard Immune Therapy Nivolumab Compared to Standard Chemotherapy for Non-small Cell Lung Cancer

Status
Active
Cancer Type
Lung Cancer
Unknown Primary
Trial Phase
Phase II
Eligibility
18 Years and older, Male and Female
Study Type
Treatment
NCD ID
NCT04310007
Protocol IDs
EA5191 (primary)
EA5191
NCI-2020-01541
Study Sponsor
ECOG-ACRIN Cancer Research Group

Summary

This phase II trial compares cabozantinib alone and the combination of cabozantinib and nivolumab to standard chemotherapy in the treatment of patients with non-squamous non-small cell lung cancer (NSCLC). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ramucirumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as docetaxel, gemcitabine hydrochloride, paclitaxel, and nab-paclitaxel, 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. Giving cabozantinib alone or in combination with nivolumab may be more effective than standard chemotherapy in treating patients with non-small cell lung cancer.

Objectives

PRIMARY OBJECTIVE:
I. To determine whether cabozantinib alone, or the combination of nivolumab and cabozantinib, as compared to standard chemotherapy alone, extends progression-free survival (PFS) for this patient population with non squamous NSCLC.

SECONDARY OBJECTIVES:
I. To evaluate the progression free survival (PFS) and best overall radiographic response rate of the targeted therapy arm of the trial.
II. To determine the overall survival for each arm of the trial.
III. To evaluate the best overall radiographic response rate for each arm of the trial.
IV. To evaluate and describe the toxicity profile of monotherapy with cabozantinib, and the combination of nivolumab and cabozantinib in this patient population with non-squamous NSCLC.

EXPLORATORY IMAGING OBJECTIVES:
I. To describe time point tumor response assessment, overall best response, progression-free survival and overall survival using the conventional Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and the exploratory revised CHOI criteria with all measurements performed by the central review.
II. To compare the progression-free survival using the RECIST1.1 imaging response assessment measurements by site study personnel to those performed by central review.

EXPLORATORY CORRELATIVE OBJECTIVE:
I. To perform correlative biomarker research on tissue and blood biospecimens collected within this trial.

OUTLINE: Patients without known molecular alterations are randomly assigned to 1 of 3 arms. Patients with known molecular alterations are assigned to Arm B.

ARM A: Patients receive cabozantinib S-malate orally (PO) once daily (QD). Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients may continue to receive therapy after investigator-assessed RECIST 1.1 defined progression, including stable clinical and performance status and have potential for continued clinical benefit.

ARM B: Patients receive cabozantinib S-malate PO QD and nivolumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients may continue to receive therapy after investigator-assessed RECIST 1.1 defined progression, including stable clinical and performance status and have potential for continued clinical benefit.

ARM C:
STEP 1: Patients receive ramucirumab IV over 30-60 minutes and docetaxel IV over 1 hour on day 1, or docetaxel IV over 1 hour on day 1 or on days 1 and 8, or gemcitabine hydrochloride IV on days 1 and 8, or paclitaxel IV over 3 hours on day 1, or nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity and at the discretion of the treating physician. Patients may continue to receive therapy after investigator-assessed RECIST 1.1 defined progression, including stable clinical and performance status and have potential for continued clinical benefit.

STEP 2: Patients receive cabozantinib S-malate PO QD and nivolumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients may continue to receive therapy after investigator-assessed RECIST 1.1 defined progression, including stable clinical and performance status and have potential for continued clinical benefit.

After the completion of study treatment, patients are followed up every 3 months for up to 3 years.