Cabozantinib Clinical Trials

What Is Cabozantinib?

Cabozantinib is an FDA-approved medication for progressive, metastatic medullary thyroid cancer and certain types of renal cell carcinoma. It is a type of drug known as a tyrosine kinase inhibitor. Cabozantinib works by targeting several proteins, including MET, vascular endothelial growth factor receptor 1-3 (VEGFR1-3), RET, AXL, FLT3, and KIT. By blocking these specific proteins, it helps to slow the growth of tumor cells and inhibit the formation of new blood vessels that tumors need to grow. This medication is also being extensively investigated for its potential use in other advanced cancers.

Uses and Conditions Under Study

Cabozantinib is approved for specific cancers and is being studied in a wide range of other conditions, primarily various types of cancer. Research involving cabozantinib includes 251 trials with a total enrollment of 37,854 participants.

• Kidney Cancers: Cabozantinib is approved for renal cell carcinoma (RCC), the most common form of kidney cancer. It is being studied in conditions such as Renal Cell Carcinoma (25 trials), Metastatic Renal Cell Carcinoma (14 trials), Stage IV Renal Cell Cancer AJCC v8 (13 trials), Clear Cell Renal Cell Carcinoma (10 trials), and Stage III Renal Cell Cancer AJCC v8 (10 trials). This medication helps by targeting pathways involved in tumor growth and blood vessel formation in these cancers.
• Liver Cancers: For advanced hepatocellular carcinoma (HCC), cabozantinib has shown promise in extending survival for patients who have progressed on other treatments like sorafenib. It is being investigated in Hepatocellular Carcinoma (14 trials) and Advanced Hepatocellular Carcinoma (6 trials).
• Other Solid Tumors: Cabozantinib is also being explored for its potential in other cancers. This includes Prostate Cancer (8 trials), where studies have shown prostate tumors may respond to it, and Colorectal Cancer (7 trials), where it aims to improve outcomes for metastatic disease. Additionally, it is being studied in a broader category of Cancer (6 trials) to assess individualized treatment strategies for advanced solid and hematological malignancies.

Dosing

Cabozantinib is available in both oral capsule and tablet forms, and in some studies, it has been administered intravenously (IV). For oral administration, it is typically taken once a day and must be swallowed whole, not crushed. Patients are often advised to take it on an empty stomach, avoiding food or drink (other than water) for 2 hours before and 1 hour after taking the medication.

The dosage of cabozantinib can vary significantly depending on the specific condition being treated and the design of the clinical trial. Doses studied range from 20 mg, 25 mg, 40 mg, 60 mg, 75 mg, 100 mg, 125 mg, to 140 mg. For example, some initial study groups have started with 20 mg, while other trials have investigated doses like 60 mg daily or 40 mg daily in combination with other therapies such as nivolumab or atezolizumab. The specific dose a participant receives in a study is determined by the trial protocol and may be adjusted based on individual response and tolerability.

Side Effects

In clinical trials involving patients with advanced malignancies, Cabozantinib was associated with several side effects. The most common side effect was diarrhea, experienced by 54.1% of patients taking Cabozantinib, compared to 23.6% on placebo. Other common side effects included:

• Fatigue: 43.9% of patients on Cabozantinib experienced fatigue, compared to 32.0% on placebo.
• Palmar-plantar erythrodysaesthesia syndrome (hand-foot syndrome): 39.2% of patients on Cabozantinib experienced this, compared to 5.3% on placebo.
• Increased aspartate aminotransferase (a liver enzyme): 39.1% of patients on Cabozantinib had elevated levels, compared to 16.3% on placebo.
• Increased alanine aminotransferase (another liver enzyme): 37.3% of patients on Cabozantinib had elevated levels, compared to 15.8% on placebo.
• Decreased appetite: 36.8% of patients on Cabozantinib experienced this, compared to 19.0% on placebo.
• Hypertension (high blood pressure): 32.5% of patients on Cabozantinib experienced this, compared to 12.0% on placebo.
• Nausea: 30.1% of patients on Cabozantinib experienced nausea, compared to 20.4% on placebo.

Clinical Trial Results

Advanced Malignancies (NCT00940225)

In a study of adults with various advanced cancers, Cabozantinib demonstrated improvements in progression-free survival (PFS) compared to placebo in several tumor types. For patients with castrate-resistant prostate cancer (CRPC), the median PFS was 5.5 months with Cabozantinib compared to 1.4 months with placebo. Significant improvements in median PFS were also observed in metastatic breast cancer (6.9 months vs 1.1 months), ovarian cancer (4.9 months vs 1.4 months), and small cell lung cancer (5.5 months vs 1.5 months) when treated with Cabozantinib compared to placebo. No difference in median PFS was observed for non-small cell lung cancer.

Overall survival (OS) for CRPC was 11.1 months for patients receiving 100 mg Cabozantinib, and 8.5 months for ovarian cancer patients on 100 mg Cabozantinib. Objective response rates (ORR) varied by cancer type in the lead-in stage of the study, with the highest rates seen in ovarian cancer (21.7% of participants), metastatic breast cancer (13.6%), and non-small cell lung cancer (10%).

Bone scan response (BSR) in CRPC was observed in 74.2% of participants receiving 100 mg Cabozantinib, with a median duration of 5.2 months.

Castrate-Resistant Prostate Cancer (NCT01347788, NCT01428219)

In a study focusing on CRPC (NCT01347788), partial responses in bone scans from baseline to week 6 were observed in 9 participants in Cohort 1, 1 participant in Cohort 2, and 6 participants in the Expansion Cohort. Another study (NCT01428219) showed that 77.3% of participants remained progression-free at 12 weeks with Cabozantinib. The median time to PSA progression was 6 weeks.

Metastatic Hormone-Receptor-Positive Breast Cancer (NCT01441947)

In a trial for women with metastatic hormone-receptor-positive breast cancer, Cabozantinib led to a bone scan response rate of 38.5%. However, no participants achieved an overall objective response by RECIST v1.1 criteria. The median overall survival was 19.6 months, and the median progression-free survival was 4.3 months.

Currently Recruiting Trials