Trial Outcomes & Findings for Magnetic Resonance Imaging in Measuring the Effect of Cabozantinib in Patients With Castrate Resistant Prostate Cancer (NCT NCT01599793)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

baseline, 2 weeks

Results posted on

2020-03-26

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Enzyme Inhibitor Therapy) 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
Overall Study STARTED	19
Overall Study COMPLETED	17
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Enzyme Inhibitor Therapy) 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
Overall Study Adverse Event	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Enzyme Inhibitor Therapy) n=17 Participants 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
Age, Continuous	68 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	17 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, 2 weeks

Population: 2 individuals had missing values for Ktrans from baseline to 24 weeks

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.

Outcome measures

Outcome measures
Measure	Treatment (Enzyme Inhibitor Therapy) n=15 Participants 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
Change in the Functional MRI Metrics Ktrans Between 2 Weeks and Baseline	0.026 per minute (or min-1) Standard Deviation 0.005

SECONDARY outcome

Timeframe: From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year

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.

Outcome measures

Outcome measures
Measure	Treatment (Enzyme Inhibitor Therapy) n=17 Participants 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
Association of Progression Free Survival (PFS) With Ktrans and ADC	5.100 month Interval 2.9 to 5.7

SECONDARY outcome

Timeframe: baseline, 2 weeks

Population: 6 individual have missing bone lesions data.

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.

Outcome measures

Outcome measures
Measure	Treatment (Enzyme Inhibitor Therapy) n=11 Participants 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
Changes in Bone Scan Response	-0.43750 score on a scale Standard Deviation 0.72744

SECONDARY outcome

Timeframe: baseline, 12 weeks, and 24 weeks

Population: Data on RECIST tumor measurements were not collected

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: At 12 weeks, 4 individual have missing PSA data.

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

Outcome measures

Outcome measures
Measure	Treatment (Enzyme Inhibitor Therapy) n=13 Participants 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
Change of PSA Between 12 Weeks and Baseline	453.04 ng/mL Standard Deviation 998.62

SECONDARY outcome

Timeframe: baseline, 12 weeks, and 24 weeks

Population: data on CTC were not collected

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline,12 weeks

Population: At 12 weeks, 3 individual have missing pain score data.

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.

Outcome measures

Outcome measures
Measure	Treatment (Enzyme Inhibitor Therapy) n=14 Participants 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
Change in Pain Scale Between 12 Weeks and Baseline	-1.35714 score on a scale Standard Deviation 3.77455

Adverse Events

Treatment (Enzyme Inhibitor Therapy)

Serious events: 4 serious events

Other events: 15 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Enzyme Inhibitor Therapy) n=17 participants at risk 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
Blood and lymphatic system disorders Neutrophil count decreased	5.9% 1/17 • Number of events 1 • Adverse events were monitored/assessed every two weeks for the first three months and then every 4 weeks thereafter (until one year). Assessment of toxicities and adverse events were graded according to the Common Toxicity Criteria (CTC), version 4.03.
Respiratory, thoracic and mediastinal disorders hospitalized with pneumaonia (Aspiration)	5.9% 1/17 • Number of events 1 • Adverse events were monitored/assessed every two weeks for the first three months and then every 4 weeks thereafter (until one year). Assessment of toxicities and adverse events were graded according to the Common Toxicity Criteria (CTC), version 4.03.
General disorders Dehydration	5.9% 1/17 • Number of events 1 • Adverse events were monitored/assessed every two weeks for the first three months and then every 4 weeks thereafter (until one year). Assessment of toxicities and adverse events were graded according to the Common Toxicity Criteria (CTC), version 4.03.
Blood and lymphatic system disorders Syncope	5.9% 1/17 • Number of events 1 • Adverse events were monitored/assessed every two weeks for the first three months and then every 4 weeks thereafter (until one year). Assessment of toxicities and adverse events were graded according to the Common Toxicity Criteria (CTC), version 4.03.

Other adverse events

Other adverse events
Measure	Treatment (Enzyme Inhibitor Therapy) n=17 participants at risk 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
General disorders Fatigue	41.2% 7/17 • Number of events 7 • Adverse events were monitored/assessed every two weeks for the first three months and then every 4 weeks thereafter (until one year). Assessment of toxicities and adverse events were graded according to the Common Toxicity Criteria (CTC), version 4.03.
Gastrointestinal disorders mucositis	5.9% 1/17 • Number of events 1 • Adverse events were monitored/assessed every two weeks for the first three months and then every 4 weeks thereafter (until one year). Assessment of toxicities and adverse events were graded according to the Common Toxicity Criteria (CTC), version 4.03.
Gastrointestinal disorders diarrhea	11.8% 2/17 • Number of events 2 • Adverse events were monitored/assessed every two weeks for the first three months and then every 4 weeks thereafter (until one year). Assessment of toxicities and adverse events were graded according to the Common Toxicity Criteria (CTC), version 4.03.
Skin and subcutaneous tissue disorders plantar erythrodysaesthesia	11.8% 2/17 • Number of events 2 • Adverse events were monitored/assessed every two weeks for the first three months and then every 4 weeks thereafter (until one year). Assessment of toxicities and adverse events were graded according to the Common Toxicity Criteria (CTC), version 4.03.
Gastrointestinal disorders elevated transaminases	100.0% 1/1 • Number of events 1 • Adverse events were monitored/assessed every two weeks for the first three months and then every 4 weeks thereafter (until one year). Assessment of toxicities and adverse events were graded according to the Common Toxicity Criteria (CTC), version 4.03.
Gastrointestinal disorders decreased appetite	11.8% 2/17 • Number of events 2 • Adverse events were monitored/assessed every two weeks for the first three months and then every 4 weeks thereafter (until one year). Assessment of toxicities and adverse events were graded according to the Common Toxicity Criteria (CTC), version 4.03.

Additional Information

Russell Szmulewitz, MD

University of Chicago

Phone: 773-702-7609

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place