Cabozantinib for Advanced Urothelial Cancer

NCT01688999 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 12020512-C-0205
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Cabozantinib is a drug that slows the growth of blood vessels that feed tumors. It is approved for medullary thyroid cancer. However, studies have shown that prostate and ovarian tumors respond to it. Researchers want see if cabozantinib can be a safe and effective treatment for urothelial cancer. Objectives: \- To test the safety and effectiveness of cabozantinib for advanced urothelial cancer. Eligibility: \- Individuals at least 18 years of age who have advanced urothelial cancer that has not responded to standard treatments. Design:

• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Tumor tissue samples will also be collected. Imaging studies will also be performed.
• Participants will take cabozantinib by mouth once per day on each day of a 28-day cycle.
• Treatment will be monitored with frequent blood tests and imaging studies.
• Participants will continue to take the study drug for as long as their cancer does not worsen and side effects are not too severe.

Conditions

Urothelial Carcinoma; Urethral Neoplasms; Urinary Bladder Neoplasms; Kidney Neoplasms

Keywords

Kidney Cancer; Tyrosine Kinase Inhibitor; Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Overall Response

  Complete Response (CR) or Partial Response (PR) to Cabozantinib (XL184) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  Median follow-up was 61.2 months

Secondary Outcomes (4)

• Overall Survival

  Median follow-up was 61.2 months

• Progression Free Survival

  Median follow-up was 61.2 months

• Number of Participants With Grade 4 Toxicity Hypomagnesium Related to Cabozantinib

  Median follow-up was 61.2 months

• Number of Participants With Serious and Non-serious Adverse Events Regardless of Attribution

  Median follow-up was 61.2 months

Study Arms (1)

Cabozantinib

EXPERIMENTAL

Administered orally at a dose of 60 mg once daily on each day of a 28-day cycle.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

60 mg by mouth (PO) daily each 28 day cycle. Treatment continues until toxicity or disease progression.

Also known as: Cometriq

Cabozantinib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort 1 only (urothelial progressive disease)
• Patients must have a histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis. Confirmation may be obtained from any Clinical Laboratory Improvement Amendments (CLIA) certified lab.
• Patients must have progressive metastatic disease. Progressive disease will be defined as new or progressive lesions on cross-sectional imaging.
• Patients must have at least one measurable site of disease
• Cohort 2 only (Bone-only)
• Patients must have a histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis. Confirmation may be obtained from any CLIA certified lab.
• Patients must not have measurable progressive disease
• Patient must have appearance of at least one new bone lesion.
• Cohort 3 (Rare histologies)
• Patient must have a histologically confirmed diagnosis of non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis including but not limited to squamous cell, neuroendocrine, adenocarcinoma including urachal and sarcomatoid. Confirmation may be obtained from any CLIA certified lab.
• Patients must have progressive metastatic disease. Progressive disease will be defined as new or progressive lesions on cross-sectional imaging.
• Patients must have at least one measurable site of disease
• All cohorts
• Patients must have been previously treated, as defined by treatment with at least one prior cytotoxic regimen or agent.
• Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of cabozantinib in patients \<18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.

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 or mitomycin within 6 weeks before the first dose of study treatment.
• Prior treatment with cabozantinib
• Prior treatment with other small molecule inhibitors of Vascular Endothelial Growth Factor Receptors (VEGFR) within less than or equal to 2 years of study enrollment.
• The subject has received radiation therapy:
• to the thoracic cavity or gastrointestinal tract within 3 months before the first dose of study treatment
• to bone or brain metastasis within 14 days before the first dose of study treatment
• to any other site(s) within 28 days before the first dose of study treatment
• The subject has received radionuclide treatment within 6 weeks before the first dose of study treatment
• The subject has received 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, before 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 Common Terminology Criteria in Adverse Events (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, leptomeningeal 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 greater than or equal to 1.3 times the laboratory upper limit of normal (ULN) within 7 days before the first dose of study treatment.
• The subject requires treatment, in therapeutic doses, with oral anticoagulants such as warfarin prior to initiation of protocol therapy. Low dose aspirin (less than or equal to 81 mg/day), lowdose warfarin (less than or equal to 1 mg/day), and low molecular weight heparin (LMWH) are permitted. Subjects will be permitted to use anticoagulation as described if treatment is required while they are enrolled on the protocol.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (6)

• Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49. doi: 10.3322/caac.20006. Epub 2009 May 27.

  PMID: 19474385 BACKGROUND

• McCaffrey JA, Hilton S, Mazumdar M, Sadan S, Kelly WK, Scher HI, Bajorin DF. Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma. J Clin Oncol. 1997 May;15(5):1853-7. doi: 10.1200/JCO.1997.15.5.1853.

  PMID: 9164195 BACKGROUND

• Vaughn DJ, Broome CM, Hussain M, Gutheil JC, Markowitz AB. Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. J Clin Oncol. 2002 Feb 15;20(4):937-40. doi: 10.1200/JCO.2002.20.4.937.

  PMID: 11844814 BACKGROUND

• Apolo AB, Nadal R, Tomita Y, Davarpanah NN, Cordes LM, Steinberg SM, Cao L, Parnes HL, Costello R, Merino MJ, Folio LR, Lindenberg L, Raffeld M, Lin J, Lee MJ, Lee S, Alarcon SV, Yuno A, Dawson NA, Allette K, Roy A, De Silva D, Lee MM, Sissung TM, Figg WD, Agarwal PK, Wright JJ, Ning YM, Gulley JL, Dahut WL, Bottaro DP, Trepel JB. Cabozantinib in patients with platinum-refractory metastatic urothelial carcinoma: an open-label, single-centre, phase 2 trial. Lancet Oncol. 2020 Aug;21(8):1099-1109. doi: 10.1016/S1470-2045(20)30202-3. Epub 2020 Jul 6.

  PMID: 32645282 RESULT

• Folio LR, Turkbey EB, Steinberg SM, Apolo AB. Viable tumor volume: Volume of interest within segmented metastatic lesions, a pilot study of proposed computed tomography response criteria for urothelial cancer. Eur J Radiol. 2015 Sep;84(9):1708-14. doi: 10.1016/j.ejrad.2015.05.026. Epub 2015 Jun 10.

  PMID: 26149529 DERIVED

• Zuo RC, Apolo AB, DiGiovanna JJ, Parnes HL, Keen CM, Nanda S, Dahut WL, Cowen EW. Cutaneous adverse effects associated with the tyrosine-kinase inhibitor cabozantinib. JAMA Dermatol. 2015 Feb;151(2):170-7. doi: 10.1001/jamadermatol.2014.2734.

  PMID: 25427282 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urethral Neoplasms; Urinary Bladder Neoplasms; Kidney Neoplasms

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urethral Diseases; Urologic Diseases; Male Urogenital Diseases; Urinary Bladder Diseases; Kidney Diseases

Results Point of Contact

• Title: Dr. Andrea Apolo
• Organization: National Cancer Institute

apoloab@nih.gov

301-480-0536

Study Officials

• Andrea B Apolo, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 14, 2012
• First Posted: September 20, 2012
• Study Start: September 11, 2012
• Primary Completion: December 11, 2017
• Study Completion: September 14, 2020
• Last Updated: October 18, 2022
• Results First Posted: October 6, 2020

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)