Cabozantinib in Men With Castration-Resistant Prostate Cancer

NCT01703065 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: 7819NCI-2012-01898P30CA015704
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot clinical trial studies cabozantinib in treating men with castration-resistant prostate cancer. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Adenocarcinoma of the Prostate; Castration-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer

Keywords

Prostate cancer; Bone metastases

Outcome Measures

Primary Outcomes (1)

• Change in Urinary N-telopeptide (uNTX) as a Marker of Bone Metabolism in Non-metastatic Patients

  Median percent change in Urinary N-Telopeptide from baseline compared to after 6 weeks of treatment with Cabozantinib in patients with non-metastatic prostate cancer.

  Baseline and 6 weeks

Secondary Outcomes (4)

• Change in Bone Specific Alkaline Phosphatase as a Marker of Bone Metabolism

  Baseline and at 6 weeks

• Change in Alkaline Phosphatase as a Marker of Bone Metabolism

  Baseline, 6 weeks

• Change in Lactic Acid Dehydrogenase (LDH) as a Marker of Bone Metabolism

  Baseline and at 6 weeks

• Changes in Biomarker Expression in Bone Biopsy Samples

  Baseline and at 6 weeks

Study Arms (2)

Cabozantinib in metastatic CRPC

EXPERIMENTAL

Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.

Drug: Cabozantinib

Cabozantinib in non-metastatic CRPC

EXPERIMENTAL

Non-Metastatic CRPC patients to receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Given orally once a day

Also known as: BMS-907351, Cometriq, XL184, cabozantinib-s-malate

Cabozantinib in metastatic CRPC; Cabozantinib in non-metastatic CRPC

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject has a proven histologic diagnosis of prostate adenocarcinoma, but may have undergone prior surgery and/or radiation.
• The subject must currently have castration resistant prostate cancer defined as 2 serial rising PSAs with a castrate level of testosterone (\<50 ng/dL).
• A subject with non-metastatic CRPC may not have received prior chemotherapy unless in the neoadjuvant or adjuvant setting \> 24 months ago and may not have received prior zoledronic acid or denosumab.
• A subject with metastatic CRPC must have bone metastases accessible for biopsy by CT guidance.
• The subject must be willing to undergo sequential biopsy of bone or bone metastases.
• Subjects must have discontinued additional hormonal (eg bicalutamide, abiraterone, estrogen) therapy prior to the first dose of cabozantinib. No antiandrogen withdrawal period is required.
• Subjects previously treated on another investigational agent must have a 2-week or more washout before starting cabozantinib, depending on the agent, toxicity profile, and half-life. However, such patients may begin tetracycline dosing after consent is signed.
• Subjects who are currently on GnRH agonists or antagonist therapy must continue androgen suppression.
• The subject is ≥18 years old on day of consent.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1.
• Organ and marrow function as follows:
• ANC ≥1500/mm3 without colony stimulating factor support.
• Platelets ≥100,000/mm3.
• Hemoglobin ≥9 g/dL.
• Total bilirubin ≤1.5 x the upper limit of normal (ULN). For subjects with known Gilbert's disease, bilirubin≤3.0 mg/dL.

You may not qualify if:

• The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (eg, cytokines or antibodies) within 3 weeks, or nitrosoureas/ mitomycin C within 6 weeks before the first dose of study treatment.
• Prior treatment with cabozantinib and other met inhibitors.
• Prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, or before the first dose of study treatment.
• The subject has received radiation therapy:
• to the thoracic cavity or gastrointestinal tract within 3 months of the first dose of study treatment.
• to bone or brain metastasis within 14 days of the first dose of study treatment.
• to any other site(s) within 28 days of the first dose of study treatment.
• The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment.
• The subject has received any other type of investigational agent within 28 days before the first dose of study treatment.
• The subject has not recovered to baseline or CTCAE ≤ Grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant AEs.
• The subject has a primary brain tumor.
• The subject has active brain metastases or epidural disease (Note: Subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. Baseline brain scans are not required to confirm eligibility.)
• The subject has prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test results at screening ≥ 1.3 x the laboratory ULN.
• The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (eg, clopidogrel). Low dose aspirin (≤ 81 mg/day), low-dose warfarin (≤ 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted.
• The subject requires chronic concomitant treatment of strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John's Wort). Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.asp; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.

Sponsors & Collaborators

• University of Washington: lead
• Prostate Cancer Foundation: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Seattle Cancer Care Alliance/University of Washington

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Limitations and Caveats

Enrollment goal was 34 evaluable patients. A total of 9 patients were consented and enrolled, 0 non-metastatic and 9 metastatic. Given that fewer patients enrolled than expected, some endpoints are not-evaluable or inconclusive.

Results Point of Contact

• Title: Dr. Celestia Higano, MD
• Organization: University of Washington

thigano@u.washington.edu

206-606-1152

Study Officials

• Celestia S Higano, MD

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Treatment is open label and non-randomized. Split in to two patient populations - metastatic CRPC and non-metastatic CRPC.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Two separate patient population arms (metastatic CRPC and non-metastatic CRPC) but both populations are given the same interventional treatment and the same safety assessments.

Study Record Dates

• First Submitted: October 5, 2012
• First Posted: October 10, 2012
• Study Start: June 18, 2013
• Primary Completion: February 2, 2015
• Study Completion: September 18, 2015
• Last Updated: December 4, 2018
• Results First Posted: December 4, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)