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

Conditions

• Metastatic Lung Non-Squamous Non-Small Cell Carcinoma
• Recurrent Lung Non-Squamous Non-Small Cell Carcinoma
• Stage IV Lung Cancer AJCC v8

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Biospecimen Collection — PROCEDURE
  Undergo blood collection
• Cabozantinib S-malate — DRUG
  Given PO
• Computed Tomography — PROCEDURE
  Undergo CT
• Docetaxel — DRUG
  Given IV
• Echocardiography Test — PROCEDURE
  Undergo ECHO
• Gemcitabine Hydrochloride — DRUG
  Given PO
• Nab-paclitaxel — DRUG
  Given IV
• Nivolumab — BIOLOGICAL
  Given IV
• Paclitaxel — DRUG
  Given IV
• Ramucirumab — BIOLOGICAL
  Given IV

Study Details

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.

Key Dates

Start date

Jul 13, 2020

Status verified

Mar 2026

Primary completion

Dec 31, 2026

Completion

Dec 31, 2026

Study Design

Enrollment

117 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Step 1, Arm A (cabozantinib S-malate)
  Patients in Step 1, Arm A receive cabozantinib S-malate PO QD. Cycles repeat every 21 days 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. Patients also undergo ECHO as clinically indicated, CT throughout the trial, and collection of blood on study.
• Experimental: Step 1, Arm B (cabozantinib S-malate, nivolumab)
  Patients in Step 1, Arm B receive cabozantinib S-malate PO QD and nivolumab IV over 30 minutes on day 1. Cycles repeat every 21 days 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. Patients also undergo ECHO as clinically indicated, CT throughout the trial, and collection of blood on study.
• Active Comparator: Step 1, Arm C (standard chemotherapy)
  Patients in Step 1, Arm C receive ramucirumab IV over 30-60 minutes and docetaxel IV over 1 hour on day 1, or docetaxel IV over 1 hour 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 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity and at the discretion of the treating physician. Patients also undergo ECHO as clinically indicated, CT throughout the trial, and collection of blood on study.
• Experimental: Step 2, Arm Z (cabozantinib S-malate, nivolumab)
  Patients in Step 2, Arm Z receive cabozantinib S-malate PO QD and nivolumab IV over 30 minutes on day 1. Cycles repeat every 21 days 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. Patients also undergo ECHO as clinically indicated, CT throughout the trial, and collection of blood on study.

Primary Outcome Measure

Progression-free survival (PFS) for patient population with non-squamous no-small cell lung cancer (NSCLC) [ Time Frame: After 58 events (From time of randomization to documented disease progression [site review of imaging] or death from any cause, whichever occurs first) ]

Locations (612)

Find similar trials in Birmingham, AL

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