Neoplasms

All Conditions

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Adenocarcinoma, Follicular

Thyroid Diseases

Carcinoma

Thyroid Neoplasms

Carcinoma, Renal Cell

Thyroid Cancer, Papillary

Adenocarcinoma

Endocrine System Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Adenocarcinoma, Papillary

Thyroid Cancer, Follicular

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Papillary Thyroid Carcinoma

Hurthle Cell Thyroid Cancer

Hypoglycemic Agents

All Drugs and Chemicals

Rosiglitazone

All subjects will receive daily XL184, and two single doses of rosiglitazone, 3 weeks apart

one 4 mg dose as a tablet followed by a second 4 mg dose 3 weeks later

rosiglitazone

XL184

The primary objective of this clinical study is to determine whether the inhibition of cytochrome P450 (CYP) isozyme CYP2C8 by XL184 observed in in vitro preclinical studies translates into the potential for clinically significant drug-drug interactions in humans. The study will measure the effect of once daily dosing of XL184 on the pharmacokinetics (PK) of rosiglitazone. The PK of XL184 when combined with rosiglitazone will be evaluated as well.

A specific objective of this study is to determine whether the interaction between XL184 and a drug such as rosiglitazone is sufficiently large enough to necessitate a dosage adjustment when used in combination with XL184, or whether the interaction would require additional therapeutic monitoring.

Rosiglitazone, commonly known as Avandia, is a prescription medicine approved by the FDA used to treat adults with Type 2 (adult-onset or non-insulin dependent) diabetes mellitus (high blood sugar). In this study, subjects will only take 2 doses of rosiglitazone. There is no intention of therapy as a result of taking rosiglitazone in this study.

A Drug-Drug Interaction Study of the Effects of XL184 (Cabozantinib) on Rosiglitazone in Subjects With Solid Tumors

A Phase 1 Drug-Drug Interaction Study of the Effects of XL184 on the Pharmacokinetics of a Single Oral Dose of Rosiglitazone in Subjects With Solid Tumors

To evaluate the effect of multiple daily doses of XL184 on single dose PK of rosiglitazone

To evaluate safety and tolerability of daily oral administration of XL184 and two single doses of rosiglitazone

To evaluate the plasma PK of XL184 after a single dose of rosiglitazone

Exelixis

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphosarcoma

Thyroid Cancer, Medullary

Flavored liquid suspension or gelatin capsules supplied in 25-mg and 100-mg strengths; daily dosing or intermittent schedule (daily dosing followed by dosing holiday in cycles)

The purpose of this study is to determine the best and safest dose of XL184 administered orally. XL184 is a new chemical entity that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration. To determine the highest safe dose, subjects will receive different amounts of the drug. The first group of subjects will receive the lowest dose of XL184. As long as no medically unacceptable side effects are noted, the dose will be increased for the next group. When the maximum tolerated dose (MTD) is reached, at least 20 subjects with Medullary Thyroid Cancer (MTC) will be enrolled to evaluate the effect of XL184 in this population.

Study of XL184 (Cabozantinib) in Adults With Advanced Malignancies

A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL184 Administered Orally to Subjects With Advanced Malignancies

Symptoms and General Pathology

Recurrence

Glioma

Glioblastoma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroepithelioma

cabozantinib, 175 mg, taken orally once per day (qd).

cabozantinib, 125 mg, taken orally once per day (qd).

Gelatin capsules supplied in 25-mg and 100-mg strengths; continuous daily dosing

The purpose of this study is to evaluate the objective response rate and 6-month progression-free survival rate of XL184 in subjects with recurrent or progressive glioblastoma multiforme. XL184 is a new chemical entity that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration.

Study of XL184 (Cabozantinib) in Adults With Glioblastoma Multiforme

A Phase 2 Study of XL184 in Subjects With Progressive or Recurrent Glioblastoma Multiforme in First or Second Relapse

Response and progression were determined per modified MacDonald Criteria and modified RANO criteria for GBM using imaging and clinical features

Duration of response is defined as the time from the first documentation of objective response that was subsequently confirmed at a visit that was ≥ 28 days later to disease progression or death due to any cause.

Overall survival (OS) is defined as the time from first dose to death due to any cause.

Cabozantinib 175 mg (L-malate salt weight; 140 mg freebase equivalent) taken orally once per day (qd)

Treatment Group A (175 mg)

Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)

Treatment Group B + Group C (125 mg)

Total

18 to <45

45 to <55

55 to <65

65 to <75

>= 75

Age, Customized

Sex: Female, Male

Race (NIH/OMB)

Exelixis Medical Information

Treatment Group A1 (175 mg) - Naive

Treatment Group B1 (125 mg) - Naive

Treatment Group C1 (125 mg) - Naive

Treatment Group A2 (175 mg) - Pre-Treated

Treatment Group B2 (125 mg) - Pre-Treated

Treatment Group C2 (125 mg) - Pre-Treated

Objective Response Rate (ORR)

Insufficient number of participants with events

Duration of Objective Response (Months)

Progression Free Survival (PFS)

Treatment Group A (175 mg) - Naive

Treatment Group A (175 mg) - Pre-Treated

Treatment Group B (125 mg) - Naive

Treatment Group B (125 mg) - Pre-Treated

Treatment Group C (125 mg) - Naive

Treatment Group C (125 mg) - Pre-Treated

Overall Survival (OS)

Treatment Group B (125 mg)

Treatment Group C (125 mg)

Overall Treatment Period

Extended Post Treatment Follow Up Period

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Neurofibroma, Plexiform

Nerve Sheath Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Neurofibromatosis

Neurofibromatosis Type 1

Cohort A (≥ 16 years - closed to accrual): Starting cabozantinib of 40 mg daily by mouth per cycle. Duration of each cycle is 28 days. Subjects will dose escalate after 2 cycles to 60 mg based on dose tolerability. Subjects who do not tolerate 40 mg will dose reduce to 20 mg. Doses will be capped at 60 mg.

Cohort B (3 - 15 years). The starting cabozantinib dose is 30 mg/m2/day by mouth per cycle. Duration of each cycle is 28 days. Subjects will dose escalate after 2 cycles to 40 mg/m2/day based on dose tolerability. Subjects who do not tolerate 30 mg/m2/day will dose reduce to 23 mg/m2/day. Doses will be capped at 60 mg/day max daily dose

Each cohort will enroll up to 24 evaluable subjects with a target minimum of 17 evaluable subjects per cohort.

This is an open label Phase II clinical trial. For both cohorts, subjects will receive cabozantinib orally in continuous cycles. Each cycle is 28 days. In absence of progressive disease or dose limiting toxicity (DLT), subjects may continue therapy for a total of 24 cycles. Subjects with radiographic response (20% or greater reduction in tumor volume) at the end of 12 cycles can continue on therapy for up to an additional year. However, for Cohort A, subjects who do not achieve 15% reduction in tumor volume after 8 cycles will be considered treatment failure and taken off study. For Cohort B, the criteria that subjects who do not achieve 15% reduction by 8 cycles are considered treatment failure and taken off study was eliminated. Subjects will be carefully monitored for toxicities associated with cabozantinib.

Cabozantinib

Chie-Schin Shih, MD

This study, "A Phase II Study of Cabozantinib (XL l84) for Plexiform Neurofibromas in Subjects with Neurofibromatosis Type I in Children and Adults diagnosed with Neurofibromatosis Type 1 (NF1) and have a type of tumor called a plexiform neurofibroma (PN). Neurofibromas are tumors that develop from the cells and tissues that cover the nerves. Plexiform neurofibromas can be disfiguring, painful, and life-threatening. These types of tumors typically do not respond well to most treatment approaches such as chemotherapy, radiation, and surgery because of their slow growth and location near vital structures of the body such as nerves, blood vessels, and the airway.

The primary objective is to determine the response rate of NF1 patients with plexiform neurofibromas treated with Cabozantinib therapy using MRI scans. The objective response rate to cabozantinib is defined as ≥ 20% reduction in tumor volume at the end of 12 cycles.

There are two cohorts: Cohort A is for patients ≥ 16 years of age and Cohort B is for patients 3 - 15 years of age. Cohort A is closed to enrollment but this study will open to Cohort B patients. This phase II open label study will evaluate adults and children with NF1 and plexiform neurofibromas treated with cabozantinib (XL184). This study will enroll subjects who either meet clinical diagnostic criteria or have an identified pathogenetic NF1 mutation. Subjects on study must have clinically significant plexiform neurofibroma defined as potentially life-threatening, impinging on vital structures or significantly impairing the quality of life from pain or other symptoms. Patients must not have lesions suspicious for malignant tumors such as MPNSTs (malignant peripheral nerve sheath tumors) and suspicious tumors must be proven negative by histopathology prior to enrollment on study. Since Cohort A is closed to accrual, this study will be open to Cohort B, patients 3 - 15 years of age that meet eligibility criteria.

For Cohort A, the study will be a Simon two-stage study design. It will be a single-arm open-label study of cabozantinib and the primary endpoint is the objective response rate (ORR) to cabozantinib at 1 year. In the first stage, 9 evaluable subjects will be accrued. If there is at least 1 response, accrual will continue to the second stage and an additional 8 evaluable subjects will be enrolled. To allow for 25% unevaluable subjects, a maximum of 24 subjects will be enrolled. Radiographic response will be evaluated as the primary endpoint with 20% volumetric MRI response of the target lesion being the threshold criteria for tumor response. A target lesion will be selected at time of enrollment and tumor evaluations will occur serially while on study.

For Cohort B, a minimum of 17 evaluable subjects will be enrolled. To allow for up to 25% unevaluable subjects, a minimum of 24 subjects will be enrolled. Based on preliminary response data and minimal toxicity in Cohort A, a 2-stage design is not felt to be necessary for Cohort B.

In Cohort A, all subjects will start cabozantinib at 40 mg. The published maximum tolerated dose (MTD) for Cabozantinib is 140 mg and the current recommended dose in Phase 3 clinical trials for subjects with medullary thyroid cancer is 100 mg. Doses of 40 mg and 60 mg continue to show efficacy in on-going phase 2 and phase 3 trials with reduced toxicity. Subjects who tolerate 40 mg for 2 cycles will escalate to 60 mg. The rationale for this is that the majority of subjects who develop toxicity do so after \>2 weeks on drug as cabozantinib has a long half-life. Subjects who experience dose-limiting toxicity at 40 mg will dose reduce to 20 mg when their toxicities resolve. Subjects without toxicity at 40mg will increase to 60mg. Subjects who experience toxicity at 60 mg will dose reduce to 40 mg. This dosing schema is designed to maximize safety and tolerability in this new population of patients.

In Cohort B, subjects will start at 30 mg/m2/day dosing. Dose will be escalated at cycle 3 if tolerated to 40 mg/m2. Subjects who experience DLT at 40 mg/m2/day will dose reduce to 30 mg/m2/day. Subjects who experience DLT at 30 mg/m2/day will dose reduce to 23 mg/m2day. Actual dosing will be based on the dosing nomogram.

Dosing will be continuous, with 28 days defined as a cycle and each cycle reporting period is day 1 to day 28. In the absence of progressive disease or dose limiting toxicity (DLT), subjects may continue on therapy for a total of 12 total cycles. Subjects who have a radiographic response (20% or greater reduction in tumor volume) on therapy at the end of 12 cycles can continue on therapy for up to an additional year. The maximum duration for treatment under this study design is 24 cycles. However, subjects who do not achieve at least 15% reduction in index tumor volume after 8 cycles (\~8 months) will be considered treatment failures and taken off study. Subjects entered on the trial will be carefully monitored for the development of cabozantinib associated toxicities, and target modifications and interruptions will be performed.

The investigational nature and objectives of this trial, the procedures and treatment involved, the risks, discomforts, and benefits, and potential alternatives therapies will be carefully explained to the subject and/or subject's parent(s) or guardian, if subject is a child,by the site Principal Investigator or designated associate investigator. When appropriate, pediatric patients will be included in all discussions. A signed informed consent document will be obtained prior to determining eligibility and entry criteria to this trial. Subjects entered on this trial will be treated with therapeutic intent and response to therapy will be closely monitored. This protocol involves greater than minimal risk but presents the potential for direct benefit to individual subjects

Schedule of study evaluations are summarized below:

Pre-Study:

* Medical history, physical exam with vital signs, blood pressure, and pulse oximetry
* Performance status to assess your ability to perform everyday tasks
* Laboratory tests including blood and urine tests for routine safety tests
* Urine pregnancy test for females of childbearing age
* Electrocardiogram (EKG) to monitor the electrical activity of the heart
* MRI of neurofibromas
* Completion of health-related questionnaires on quality of life, pain assessment, and PN symptom checklist (upon study entry)
* Research blood draws ( 2 tablespoons) to evaluate the tumor's response to treatment and the action of cabozantinib in the body over a period of time (Upon study entry on Cycle 1 Day 1, predose and 4-hours post dose)

During Study Treatment:

End of Cycles 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24 or Early Termination (additional visit that is not within the specified times mentioned.)

* Medical History
* Physical exam with vital signs, blood pressure and pulse oximetry
* Performance Status
* Review of Subject Diary
* Urine pregnancy test for females of childbearing age at end of cycles 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24
* Electrocardiogram (EKG) to monitor the electrical activity of the heart at end of cycles 1, 2, 4, 6, 9, 12, 16, 20, 24

End of Cycles 1 - 24, or Early Termination

* Laboratory tests including blood and urine tests for routine safety tests

End of Cycles 4, 8, 12, 18, 24, or Early Termination

* MRI of neurofibromas
* Completion of health-related questionnaires on quality of life, pain assessment, and PN symptom checklist

Cycles 1, 2, 3, 4

* Research blood draws ( 2 tablespoons) to evaluate the tumor's response to treatment and the action of cabozantinib in the body over a period of time

Phone Calls will be made at the end of cycles 13, 15, 17, 19, 21, and 23 to assess drug compliance and toxicity

The protocol PI and clinical coordinator will review the subject eligibility, study progress, safety issues, protocol deviations and adverse events. A Data Safety Monitoring Board (DSMB) and a medical monitor has been established for the purpose of ensuring data compliance and regular monitoring of this trial. The medical monitor is a qualified physician and is not associated with this particular protocol. The medical monitor is specifically required to review all unanticipated problems involving risk to subjects or others, serious adverse events and deaths associated with the protocol and provide an unbiased written report of the event.

An early stopping rule will be invoked for both cohorts to potentially prevent accrual of subjects onto the study in the event that Cabozantinib is associated with a higher than acceptable rate of dose-limiting toxicity (DLT) requiring removal from study (set at 10% or higher) during the first 2 cycles. Toxicity will be continuously monitored. If at any time \>2 of the first 10 subjects or 4 or more of the first 15 total subjects are removed for DLT, then accrual will be stopped until the DSMB reviews safety and efficacy data for the study and recommends termination or despite the DLT (because of the benefit:risk assessment or other reasoning) recommends reopening recruitment. Boundaries for DSMB for consideration of terminating each cohort (both cohort A and B) would be the same.

The sample size for this trial is based on the safety and feasibility factors. The data needed is based on risk versus benefit. For feasibility, we expect at least efficacy of a 25% response rate. For safety reasons, subjects who do not achieve at least a 15% reduction in tumor volume will not be continued beyond 8 courses, as the likelihood of achieving a response (20% reduction in tumor volume) by 12 months is minimal. These subjects will be discontinued from the trial and counted in an "Intent to Treat" analysis as evaluable and as failures.

All analyses for outcome results will be based on evaluable subjects. Definitions of evaluable include: 1.) Evaluation for toxicity (subject who received at least one dose of study drug and removed from treatment for toxicity are evaluable. Any subject who completed one full cycle of therapy is evaluable for toxicity); 2.)Evaluation for response (subjects who have completed at least two cycles of therapy and have had their first follow-up MRI evaluation. Subjects who did not respond and are later found to have a target tumor other than a plexiform neurofibroma (e.g. malignant peripheral nerve sheath tumor) are not evaluable for response).

Cohort A: Single-arm open label two-stage Simon optimal study design Cohort B: Single-arm open-label study design

Cabozantinib for Plexiform Neurofibromas (PN) in Subjects With NF1 in Children and Adults

A Phase II Study of Cabozantinib (XL184) for Plexiform Neurofibromas in Subjects With Neurofibromatosis Type 1 in Children and Adults

We will estimate the objective response rate (ORR) as defined by 20% volumetric MRI response of the target lesion to cabozantinib at 12 months in adolescents and adults with Neurofibromatosis type 1 (NF1) plexiform neurofibromas by volumetric MRI imaging.

This is the number of participants with one or more adverse events.

University of Alabama at Birmingham

Principal Investigator

Cohort A (≥ 16 years - closed to accrual): Starting cabozantinib of 40 mg daily by mouth per cycle. Duration of each cycle is 28 days. Subjects will dose escalate after 2 cycles to 60 mg based on dose tolerability. Subjects who do not tolerate 40 mg will dose reduce to 20 mg. Doses will be capped at 60 mg.

Each cohort A and B will enroll up to 24 evaluable subjects with a target minimum of 17 evaluable subjects per cohort.

Cabozantinib: This is an open label Phase II clinical trial. Subjects will receive cabozantinib orally in continuous 28 day cycles. In absence of progressive disease or dose limiting toxicity (DLT), subjects may continue therapy for a total of 24 cycles. Subjects with 20% or greater reduction in tumor volume at the end of 12 cycles can continue on therapy for up to an additional year. For Cohort A, subjects who do not achieve 15% reduction in tumor volume after 8 cycles will be considered treatment failure and taken off study.

Cohort A

Cohort B (3 - 15 years). The starting cabozantinib dose is 30 mg/m2/day by mouth per cycle. Duration of each cycle is 28 days. Subjects will dose escalate after 2 cycles to 40 mg/m2/day based on dose tolerability. Subjects who do not tolerate 30 mg/m2/day will dose reduce to 23 mg/m2/day. Doses will be capped at 60 mg/day max daily dose

Each cohort A and B will enroll up to 24 evaluable subjects with a target minimum of 17 evaluable subjects per cohort.

Cabozantinib: This is an open label Phase II clinical trial. Subjects will receive cabozantinib orally in continuous 28 day cycles. In absence of progressive disease or dose limiting toxicity (DLT), subjects may continue therapy for a total of 24 cycles. Subjects with 20% or greater reduction in tumor volume at the end of 12 cycles can continue on therapy for up to an additional year. For Cohort B, the criteria that subjects who do not achieve 15% reduction by 8 cycles are considered treatment failure and taken off study was eliminated.

Cohort B

There are two cohorts. Cohort A had 23 subjects at baseline and Cohort B had 22 subjects at baseline. The overall total was 45 subjects at baseline.

Age, Continuous

Ethnicity (NIH/OMB)

Overall Study

Evaluable subjects for tumor volume in mm\^\^3

There are two cohorts with different numbers of evaluable subjects in each.

Volumetric Response

Karen Cole-Plourde, Program Director -NFCTC

Cohort A (≥ 16 years - closed to accrual): Starting cabozantinib of 40 mg daily by mouth per cycle. Duration of each cycle is 28 days. Subjects will dose escalate after 2 cycles to 60 mg based on dose tolerability. Subjects who do not tolerate 40 mg will dose reduce to 20 mg. Doses will be capped at 60 mg.

Each cohort A and B will enroll up to 24 evaluable subjects with a target minimum of 17 evaluable subjects per cohort.

Cabozantinib: This is an open label Phase II clinical trial. For both cohorts, subjects will receive cabozantinib orally in continuous cycles. Each cycle is 28 days. In absence of progressive disease or dose limiting toxicity (DLT), subjects may continue therapy for a total of 24 cycles. Subjects with radiographic response (20% or greater reduction in tumor volume) at the end of 12 cycles can continue on therapy for up to an additional year. For Cohort A, subjects who do not achieve 15% reduction in tumor volume after 8 cycles will be considered treatment failure and taken off study.

Cohort B (3 - 15 years). The starting cabozantinib dose is 30 mg/m2/day by mouth per cycle. Duration of each cycle is 28 days. Subjects will dose escalate after 2 cycles to 40 mg/m2/day based on dose tolerability. Subjects who do not tolerate 30 mg/m2/day will dose reduce to 23 mg/m2/day. Doses will be capped at 60 mg/day max daily dose

Each cohort A and B will enroll up to 24 evaluable subjects with a target minimum of 17 evaluable subjects per cohort.

Cabozantinib: This is an open label Phase II clinical trial. For both cohorts, subjects will receive cabozantinib orally in continuous cycles. Each cycle is 28 days. In absence of progressive disease or dose limiting toxicity (DLT), subjects may continue therapy for a total of 24 cycles. Subjects with radiographic response (20% or greater reduction in tumor volume) at the end of 12 cycles can continue on therapy for up to an additional year. For Cohort B, the criteria that subjects who do not achieve 15% reduction by 8 cycles was eliminated.

There were a total of 19 evaluable subjects from Cohort A and 21 for Cohort B.

The Change in Tumor Size Based on Radiographic Assessment

Cohort A (≥ 16 years - closed to accrual): Starting cabozantinib of 40 mg daily by mouth per cycle. Duration of each cycle is 28 days. Subjects will dose escalate after 2 cycles to 60 mg based on dose tolerability. Subjects who do not tolerate 40 mg will dose reduce to 20 mg. Doses will be capped at 60 mg.

Each cohort A and B will enroll up to 24 evaluable subjects with a target minimum of 17 evaluable subjects per cohort.

Cabozantinib: This is an open label Phase II clinical trial. For both cohorts, subjects will receive cabozantinib orally in continuous cycles. Each cycle is 28 days. In absence of progressive disease or dose limiting toxicity (DLT), subjects may continue therapy for a total of 24 cycles. Subjects with radiographic response (20% or greater reduction in tumor volume) at the end of 12 cycles can continue on therapy for up to an additional year. However, for Cohort A, subjects who do not achieve 15% reduction in tumor volume after 8 cycles will be considered treatment failure and taken off study.

Number of Participants With Adverse Events

Cohort A (≥ 16 years - closed to accrual): Starting cabozantinib of 40 mg daily by mouth per cycle. Duration of each cycle is 28 days. Subjects will dose escalate after 2 cycles to 60 mg based on dose tolerability. Subjects who do not tolerate 40 mg will dose reduce to 20 mg. Doses will be capped at 60 mg.

Each cohort A and B will enroll up to 24 evaluable subjects with a target minimum of 17 evaluable subjects per cohort.

Cabozantinib: This is an open label Phase II clinical trial. Subjects will receive cabozantinib orally in continuous 28 day cycles. In absence of progressive disease or dose limiting toxicity (DLT), subjects may continue therapy for a total of 24 cycles. Subjects with 20% or greater reduction in tumor volume at the end of 12 cycles can continue on therapy for up to an additional year. However, for Cohort A, subjects who do not achieve 15% reduction in tumor volume after 8 cycles will be considered treatment failure and taken off study.

Cohort B (3 - 15 years). The starting cabozantinib dose is 30 mg/m2/day by mouth per cycle. Duration of each cycle is 28 days. Subjects will dose escalate after 2 cycles to 40 mg/m2/day based on dose tolerability. Subjects who do not tolerate 30 mg/m2/day will dose reduce to 23 mg/m2/day. Doses will be capped at 60 mg/day max daily dose.

Each cohort A and B will enroll up to 24 evaluable subjects with a target minimum of 17 evaluable subjects per cohort.

Cabozantinib: This is an open label Phase II clinical trial. Subjects will receive cabozantinib orally in continuous 28 day cycles. In absence of progressive disease or dose limiting toxicity (DLT), subjects may continue therapy for a total of 24 cycles. Subjects with 20% or greater reduction in tumor volume at the end of 12 cycles can continue on therapy for up to an additional year. For Cohort B, the criteria that subjects who do not achieve 15% reduction by 8 cycles are considered treatment failure and taken off study was eliminated.

Prostatic Neoplasms

Neoplasm Metastasis

Genital Neoplasms, Male

Genital Diseases

Genital Diseases, Male

Prostatic Diseases

Neoplastic Processes

Enzyme Inhibitors

Patients receive cabozantinib PO QD. Treatment continues in the absence of disease progression or unacceptable toxicity.

cabozantinib

laboratory biomarker analysis

magnetic resonance imaging

Russell Szmulewitz

This study is being done to help researchers understand more about prostate cancer that has spread to the bones by using the newest magnetic resonance imaging (MRI) techniques and to better understand the effect of an experimental drug called XL184 (or cabozantinib) on bone disease. The other purposes of the study are to better understand the effect of XL184 on prostate cancer progression, bone pain, and on any cancer cells that patients may have circulating within the blood (called circulating tumor cells)

PRIMARY OBJECTIVES:

I. To determine effect of XL184 on the functional MRI metrics Ktrans and apparent diffusion coefficient (ADC) within castrate resistant prostate cancer bone metastases.

SECONDARY OBJECTIVES:

I. To quantify progression free survival in men with castrate resistant prostate cancer (CRPC) treated with XL184 according to Prostate Cancer Working Group criteria.

II. To correlate and changes in MRI based functional metrics with bone scan, prostate specific antigen (PSA), Response Evaluation Criteria in Solid Tumors (RECIST) response criteria, circulating tumor cells (CTC) number and with changes in pain.

III. To explore c-MET, phospho-c-MET staining on circulating tumor cells as a predictive biomarker for response and duration of response to XL-184.

OUTLINE:

Patients receive cabozantinib orally (PO) once daily (QD). Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Magnetic Resonance Imaging in Measuring the Effect of Cabozantinib in Patients With Castrate Resistant Prostate Cancer

A Phase II Study of MRI Based Functional Imaging for the Evaluation of Bone Metastasis in Men With Castrate Resistant Prostate Cancer Receiving XL184

Ktrans is a measurement calculating the volume transfer constant of the contrast reagent and essentially is a measurement of vascular perfusion.

To determine the effect of XL184 on the functional MRI metrics Ktrans, Ktrans parameters were measured at baseline, two week time-point, 12 weeks, and 24 weeks for disease monitoring. Change between baseline and 2 weeks reported.

Time to progression or progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

The approximate survival after standard therapies in this setting is bleak and in the order of months.

Too few events for a meaningful statistical analysis; no significant results were obtained in Cox regression analyses.

Therefore, we calculated the median PFS time and its 95% confidence interval.

Bone Scan Response at weeks 2, 12, and 24 were collected. Change between baseline and 2 weeks are reported Bone Scan Response were measured as increase, decrease, or stable of bone lesions and scored as 1, -1, or 0, respectively, where higher values represent a worse outcome.

The protocol proposed to collect RECIST tumor measurements at weeks 0, 12, and 24.

However, the data were not collected

PSA at weeks 0, 12, and 24 were collected. Change between baseline and 12 weeks are reported

The protocol proposed to collect CTC measurements at weeks 0, 12, and 24. However, the data were not collected

Pain scores are measured at baseline and weeks 12, and 24. Change between baseline and 12 weeks are reported .

In the pain score ranged from 0 to 10. 10 denotes most pain.

NorthShore University HealthSystem

University of Chicago

Assessment of toxicities and adverse events were graded according to the Common Toxicity Criteria (CTC), version 4.03.

Patients receive cabozantinib PO QD. Treatment continues in the absence of disease progression or unacceptable toxicity.

cabozantinib: Given PO

laboratory biomarker analysis: Correlative studies

magnetic resonance imaging: Undergo MRI

Treatment (Enzyme Inhibitor Therapy)

United States

Region of Enrollment

Russell Szmulewitz, MD

The least square means of ktrans at different time points (baseline, 2 weeks, 12 weeks, 24 weeks) are estimated by a linear mixed model. Comparison of means at different time points were performed. The primary result reported below is for the difference of means between 2 weeks and baseline.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Drug-Drug Interaction Study of the Effects of XL184 (Cabozantinib) on Rosiglitazone in Subjects With Solid Tumors	NCT01100619	Papillary Thyro... Follicular Thyr... Huerthle Cell T... Renal Cell Carc...	rosiglitazone XL184	18 Years -	Exelixis
Study of XL184 (Cabozantinib) in Adults With Advanced Malignancies	NCT00215605	Lymphoma Cancer Thyroid Carcino...	XL184	18 Years -	Exelixis
Study of XL184 (Cabozantinib) in Adults With Glioblastoma Multiforme	NCT00704288	Glioblastoma Mu...	XL184	18 Years -	Exelixis
Cabozantinib for Plexiform Neurofibromas (PN) in Subjects With NF1 in Children and Adults	NCT02101736	NF1 Neurofibromatos... Plexiform Neuro...	Cabozantinib	3 Years -	University of Alabama at Birmingham
Magnetic Resonance Imaging in Measuring the Effect of Cabozantinib in Patients With Castrate Resistant Prostate Cancer	NCT01599793	Bone Metastases Castrate-resist... Recurrent Prost... Stage IV Prosta...	cabozantinib laboratory biom... magnetic resona...	-	University of Chicago
Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer	NCT00704730	Thyroid Cancer	XL184 Placebo	18 Years -	Exelixis
Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib	NCT01908426	Hepatocellular ...	Cabozantinib ta... Placebo tablets	18 Years -	Exelixis
Cabozantinib for Adults With Advanced Soft Tissue Sarcoma	NCT01755195	Refractory Soft...	Cabozantinib	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Cabozantinib for Plexiform Neurofibromas (PN) in Subjects With NF1 in Children and Adults	NCT02101736	NF1 Neurofibromatos... Plexiform Neuro...	Cabozantinib	3 Years -	University of Alabama at Birmingham
Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer	NCT00704730	Thyroid Cancer	XL184 Placebo	18 Years -	Exelixis
Safety Study of XL184 (Cabozantinib) in Combination With Temozolomide and Radiation Therapy in the Initial Treatment of Adults With Glioblastoma	NCT00960492	Glioblastoma Giant Cell Glio... Gliosarcoma	XL184 temozolomide temozolomide Radiation Thera... temozolomide	18 Years -	Exelixis
Cabozantinib for Adults With Advanced Soft Tissue Sarcoma	NCT01755195	Refractory Soft...	Cabozantinib	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Study of Multiple Doses and Regimens of XL184 (Cabozantinib) in Subjects With Grade IV Astrocytic Tumors in First or Second Relapse	NCT01068782	Astrocytic Tumo...	XL184	18 Years -	Exelixis

Spots Global Cancer Trial Database for xl184

Every month we try and update this database with for xl184 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for xl184

Every month we try and update this database with for xl184 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for xl184 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.