Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Lung Neoplasms

Carcinoma

Brain Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Patients will receive cabozantinib at 60 mg orally once daily and continue on treatment until disease progression, death or unacceptable adverse events.

Treatment cycles are 4 weeks in duration

cabozantinib

Liza Villaruz, MD

This is an open-label phase II clinical trial designed to allow a preliminary assessment of the efficacy and safety of cabozantinib in unselected Non-Small Cell Lung Cancer (NSCLC) patients with metastases to the brain and in the subset of patients with c-MET amplified Non-Small Cell Lung Cancer with metastases to the brain. Previously treated patients with non-squamous NSCLC who have had brain metastases at any point in their treatment history are eligible for enrollment on this clinical trial. Patients with clinically asymptomatic untreated brain metastases will be allowed on trial at the discretion of the treating investigator. Patients who have undergone treatment for their brain metastases with Whole-Brain Radiation Therapy (WBRT), stereotactic radiosurgery (SRS) or surgery must be clinically stable and recovered from all procedures at the time of study enrollment.

This is a Phase 2, single-arm, open-label study of cabozantinib in subjects with molecularly unselected Non-Small Cell Lung Cancer (NSCLC) with metastases to the brain and in patients with c-MET amplified Non-Small Cell Lung Cancer (NSCLC) with metastases to the brain.

Patients will receive cabozantinib at 60 mg orally once daily and continue on treatment until disease progression, death or unacceptable adverse events. Treatment cycles are 4 weeks in duration.

The primary endpoint is Overall Response Rate (ORR) in both the unselected NSCLC population and the molecularly selected patients on the basis of c-MET amplification.

Trial of Cabozantinib (XL184) in Non-Small Cell Lung Cancer With Brain Metastases

A Single-Arm Phase II Clinical Trial of Cabozantinib (XL184) in Patients With Previously Treated Non-Small Cell Lung Cancer (NSCLC) With Brain Metastases With and Without C Met Amplification

The proportion of response-evaluable patients who achieve Complete Response (CR) or Partial Response (PR) as best response by RECIST v1.1 criteria. Per RECIST v1.1, Complete Response (CR) is defined as disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

Proportion of response-evaluable patients that experienced Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) as best response (RECIST v1.1 criteria) per the total study population criteria. Per RECIST v1.1, Complete Response (CR) is defined as disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Stable Disease (SD) is defined as, neither sufficient shrinkage (compared to baseline) to qualify for partial or complete response (CR or PR) nor sufficient increase (taking as reference the smallest sum of diameters at baseline or while on study, whichever is smallest) to qualify for progressive disease (PD).

Progression-free survival is the time measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression), whichever occurs first, with progression defined by RECIST v 1.1. Progressive disease (PD) is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

The length of time from the start of treatment that patients remain alive, until death from any cause.

Time from initiation of study treatment to disease progression per RECIST v1.1, excluding death from causes unrelated to the disease. As defined by RECIST v 1.1. Progressive disease (PD) is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Worst Grade of Adverse Events Reported as assessed by the investigator. Severity/grade defined by the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Subjects monitored continuously for Adverse Events (AE's) throughout the study and for 30 days after the last dose of study treatment.

Exelixis

Assistant Professor of Medicine

Serious Adverse Events are defined as grade 3 and higher toxicity events, per CTCAE v4.0

Cabozantinib - 60 mg orally, once daily (4 weeks treatment cycles)

Treatment until disease progression, death or unacceptable adverse events.

Cabozantinib (XL184)

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

c-Met, also called tyrosine-protein kinase Met or hepatocyte growth factor receptor (HGFR), is a protein that in humans is encoded by the MET gene. Over-expression of c-Met protein has been associated with poor prognosis in some solid tumors.

c-MET amplification

Histology

Stage 0. Cancer in situ; the cancer is only located in the place of origin.

Stage I. Small tumor with no deep growth into surrounding tissues; no spread to the lymph nodes or other body parts.

Stage II and Stage III. Larger cancers or tumors that have grown more deeply into surrounding tissue and may have spread to lymph nodes (only).

Stage IV. Cancer has spread to other body organs (metastasis).

Stage of Disease

Barbara Stadterman, MPH MCCR

Patients evaluable for response: Received at least one dose of study drug, and, underwent at least one radiologic scan follow-up.

Overall Response

As no patients who received at least one dose of study drug and underwent at least one follow-up radiologic scan were able to be evaluated later than 15 weeks, this endpoint cannot be assessed.

Disease Control Rate (DCR)

Only one patient was assessed as having disease progression.

Progression-free Survival (PFS)

All patients

c-MET positive patients (only)

"All patients" includes all 5 of the patients for whom survival data were available, regardless of c-MET status. "c-MET positive patients" (only) does not include patients for who c-MET status was not positive.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Trial of Cabozantinib (XL184) in Non-Small Cell Lung Cancer With Brain Metastases	NCT02132598	Non Small Cell ... Metastases to t...	cabozantinib	18 Years -	University of Pittsburgh
Trial of Cabozantinib (XL184) in Non-Small Cell Lung Cancer With Brain Metastases	NCT02132598	Non Small Cell ... Metastases to t...	cabozantinib	18 Years -	University of Pittsburgh

Spots Global Cancer Trial Database for metastases to the brain