Cabozantinib in Advanced Solid Malignancies

Study Overview
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Brief Summary
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This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. Investigational means that the drug is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of cancer. It also means that the FDA has not approved the drug for this type of cancer, or for any use outside of research studies. When cancer spreads from the primary tumor, one of the most commons sites it spreads to is bone. When cancer spreads to bone there can be significant symptoms such as pain. Cabozantinib works by blocking signaling that leads to cancer growth as well as blocking the growth of new blood vessels (angiogenesis) that help to feed a tumor. Cabozantinib has been studied or is being studied in research studies as a possible treatment for various types of cancer, including prostate cancer, brain cancer, thyroid cancer, lung cancer and kidney cancer. Previous clinical research studies indicate that cabozantinib may also have activity against cancer once it has spread to the bones. The purpose of this study is to find out if cabozantinib is effective in treating cancer that has spread to the bone.

Detailed Description
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Cabozantinib is a tablet that the subject will take by mouth. The subject will take it once per day. The study treatment with cabozantinib will be divided into 28 day cycles. A member of the study staff will give the subject a drug diary and explain to the subject how to use it to record doses of cabozantinib. This diary will also contain specific instructions about how the subject take cabozantinib. Every 28 days the subject will undergo the following procedures: Physical examination, questions about any side effects the subject may have, blood samples for routine laboratory tests and research tests, urine sample, electrocardiogram (EKG), and questionnaires to measure quality of life and level of pain. Every two months the subject will undergo a CT scan or MRI to evaluate the subjects disease. The investigators would like the subject to return to the study clinic for follow-up procedures about 4-5 weeks after the last dose of cabozantinib. The subject can continue to receive the study drug for as long as their disease does not worsen and the subject do not experience unacceptable side effects.

Official Title
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Phase II Trial of Cabozantinib (XL184) in Patients With Advanced Solid (Non-breast, Non-prostate) Malignancies and Bony Metastases

Conditions
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Lung Cancer, Solid Tumor (Not Breast or Prostate Cancers)

Intervention / Treatment
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* Drug: Cabozantinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic diagnosis of a solid tumor (not breast or prostate) that is metastatic and refractory to or progressed following standard therapies Has bony metastases Agree to use medically accepted methods of contraception Exclusion Criteria: Pregnant or breastfeeding Received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents within 3 weeks of study entry(6 weeks for nitrosoureas/mitomycin C) Received radiation to the thoracic cavity/GI tract (within 3 months of study entry), to bone or brain metastasis (within 14 days) or to any other site within 28 days Received prior treatment with small molecule kinase inhibitor or hormonal therapy within 14 days/5 half-lives Received therapy with another investigational agent within past 28 days Has not recovered from toxicities due to prior therapies Primary brain tumor Active brain metastases or epidural disease Uncontrolled significant intercurrent or recent illness Allergy or hypersensitivity to components of the study treatment formulation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Cabozantinib | Drug: Cabozantinib<br>* 60 mg daily by mouth<br>* Other names: XL184;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Bone Bio-marker Response | Effect of cabozantinib on bone biomarkers of osteoblast and osteoclast activity. The bio-markers of interest were serum C-terminal telopeptide (Ctx), urine N-terminal telopeptide (Ntx), serum (Ntx). Participants were considered to have a response if there was at least a 40% decrease in the bio-marker concentration. | 8 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Skeletal-related Events (SRE) | The number of patients that experience a SRE in patients treated with cabozantinib (SRE defined as pathologic fracture, cord compression, radiation or surgery to bone, hypercalcemia) | 2 years | 
| Quality of Life as Assessed by FACT-G | Quality of life as measured by the Functional Assessment of Cancer Therapy - General (FACT-G). FACT-G assesses patients' physical, social/family, emotional, and functional well-being. The total score can range from 0 to 108, with lower scores indicating higher quality of life. Patients without QOL scores at cycle 3 day 1 had their score from their last assessment carried forward. | From baseline to Cycle 3 Day 1 (approximately 2 months) | 
| Overall Tumor Response Rate | The number of participants with a complete or partial response as measured by bone scan or PET-CT scan using. Response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the Longest Diameter (LD) of target lesions, taking as reference the baseline sum LD | 2 years | 
| MET Amplification in Tumor Sample | Response will be correlated with specific tumor genotype (MET amplification). | 2 years | 
| Response to Cabozantinib in Bone Metastatic Disease | Response to cabozantinib in bone metastatic disease as measured by bone scan or PET-CT scan | 2 years | 
| Time to SRE | Time to SRE in patients treated with cabozantinib (SRE defined as pathologic fracture, cord compression, radiation or surgery to bone, hypercalcemia) | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic, Refractory, Relapsed