Study of Cabozantinib (XL184) in Adults With Advanced Malignancies

NCT00940225 | Completed Phase 2 Results DMC

• 1 other identifier: XL184-203
• Study Type: interventional
• Target: 730
• Locations: 5 countries
• Sites: 47

Brief Summary

This is a Phase 2 study to evaluate the efficacy and safety of cabozantinib (XL184) in subjects with selected advanced tumor types.

Conditions

Solid Tumors; Cancer

Keywords

Metastatic Breast Cancer (MBC); Melanoma; Stomach or Gastroesophageal Junction Carcinoma (GEJ); Hepatocellular Carcinoma (HCC); Small Cell Lung Cancer (SCLC); Non-Small Cell Lung Cancer (NSCLC); Ovarian Cancer; Pancreatic Cancer; Prostate Cancer

Outcome Measures

Primary Outcomes (3)

• Objective Response Rate (ORR) - LEAD IN STAGE, RDT Cohorts and NRE Ovarian Cohort Only

  Objective response rate (ORR) per modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.0 per investigator The analysis of ORR in the RDT Cohorts were defined as the proportion of subjects with a best overall response of confirmed complete response (CR) or partial response (PR) per mRECIST 1.0 during the 12-week Lead-In Stage. In the NRE Ovarian Cohort, mRECIST 1.1 was used. ORR for the NRE CRPC Cohorts was not a primary objective and is therefore not captured in the table below.

  From initial dose through final study visit up to 44 months

• Bone Scan Response (BSR) - NRE, CRPC

  The reduction of bone scan lesion area (BSLA) by \> 30% was used as the quantitative measure of BSR. BSR was a primary outcome measure for only the NRE CRPC Cohorts.

  From initial dose through final study visit up to 15 months

• Progression-Free Survival (PFS) - Randomized Stage, RDT Cohorts Only

  Progression Free Survival during the Randomized Stage (Randomized Population)

  From initial dose through final study visit up to 44 months

Secondary Outcomes (4)

• Duration of Objective Response (OR) - Responders From Lead-in Stage

  From initial dose through final study visit up to 44 months

• Progression Free Survival (PFS) - Throughout the Study

  From initial dose through final study visit up to 44 months

• Duration of Bone Scan Response - NRE Cohorts, CRPC Only

  From initial dose through final study visit up to 15 months

• Overall Survival (OS) - NRE Cohorts, CRPC and Ovarian Only

  From initial dose through final study visit up to 15 months

Study Arms (7)

Lead-in Stage - cabozantinib (XL184)

EXPERIMENTAL

Open Label, cabozantinib, 100 mg, po QD for 12 weeks.

Drug: Cabozantinib

Randomized Stage - cabozantinib (XL184)

EXPERIMENTAL

Blinded, cabozantinib, 100 mg, po QD until disease progression.

Drug: Cabozantinib

Randomized Stage - placebo

PLACEBO COMPARATOR

Blinded, placebo, 100 mg, po QD until disease progression.

Drug: Placebo

Open-Label Extension - cabozantinib (XL184)

EXPERIMENTAL

Open Label, cabozantinib, for subjects that were on placebo during the randomized stage, 100 mg, po QD until disease progression or unacceptable toxicity.

Drug: Cabozantinib

Non-Randomized Expansion (NRE) Cohort - Castrate Resistant Prostate Cancer (CRPC), 100mg

EXPERIMENTAL

Open Label, cabozantinib, 100 mg, po QD until disease progression or unacceptable toxicity.

Drug: Cabozantinib

Non-Randomized Expansion (NRE) Cohort - Castrate Resistant Prostate Cancer (CRPC), 39.4mg

EXPERIMENTAL

Open Label, cabozantinib, 39.4, po QD until disease progression or unacceptable toxicity.

Drug: Cabozantinib

A. Non-Randomized Expansion (NRE) Cohort - Ovarian

EXPERIMENTAL

Open Label, cabozantinib, 100 mg, po QD until disease progression or unacceptable toxicity.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Also known as: XL184

A. Non-Randomized Expansion (NRE) Cohort - Ovarian; Lead-in Stage - cabozantinib (XL184); Non-Randomized Expansion (NRE) Cohort - Castrate Resistant Prostate Cancer (CRPC), 100mg; Non-Randomized Expansion (NRE) Cohort - Castrate Resistant Prostate Cancer (CRPC), 39.4mg; Open-Label Extension - cabozantinib (XL184); Randomized Stage - cabozantinib (XL184)

Placebo DRUG

Randomized Stage - placebo

Eligibility Criteria

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

You may qualify if:

• The subject has a cytologically or histologically and radiologically confirmed, advanced, recurrent, or metastatic solid tumor of the nine types listed below:
• Pancreatic Cancer
• Castration-Resistant Prostate Cancer (CRPC)
• Hepatocellular Carcinoma (HCC)
• Gastric or Gastroesophageal Junction Cancer
• Melanoma
• Small Cell Lung Cancer (SCLC)
• Ovarian cancer, primary peritoneal or fallopian tube carcinoma
• Breast cancer that is one of the following subtypes: estrogen receptor positive breast cancer, estrogen receptor/progesterone receptor/HER2-negative (triple-negative), or inflammatory (regardless of receptor status) disease histology
• Non-Small Cell Lung Cancer (NSCLC)
• Certain requirements for prior therapies may apply
• The subject has documented progressive disease at screening
• Subjects having any tumor type of other than CRPC must have at least one lesion that is not within a previously irradiated field and is measurable on CT or MRI scan
• The subject has recovered to baseline or CTCAE ≤ Grade 1 from toxicities related to prior treatment (some exceptions apply)
• The subject is ≥ 18 years old on the day of consent

You may not qualify if:

• The subject has experienced clinically-significant hematemesis or hemoptysis of \>0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
• The subject has a cavitating pulmonary lesion(s) or a pulmonary lesion abutting or encasing a major blood vessel
• Certain restrictions on prior treatments apply
• The subject has known symptomatic or uncontrolled brain metastases or epidural disease
• The subject has prothrombin time/International Normalized Ratio (PT/INR) or partial thromboplastin time (PTT) test results that are above (1.3x)the laboratory upper limit of normal
• The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or Coumadin-related agents, heparin, thrombin or FXa inhibitors, and antiplatelet agents (low-dose aspirin (≤81 mg/day), low-dose warfarin (≤1mg/day, and prophylactic low molecular weight heparin (LMWH) are permitted)
• The subject has a corrected QT interval(QTcF)\>500 ms at screening
• The subject has uncontrolled, significant intercurrent illness
• The subject is unable to swallow capsules
• The subject is pregnant or breastfeeding
• The subject has a previously-identified allergy or hypersensitivity to components of the study treatment formulation
• The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
• The subject has had another diagnosis of malignancy requiring systemic treatment within the last two years, unless non-melanoma skin cancer, in-situ carcinoma of the cervix, or superficial bladder cancer

Sponsors & Collaborators

• Exelixis: lead

Study Sites (47)

Pinnacle Oncology of Arizona

Scottsdale, Arizona, 85258, United States

Location

University of California Davis Cancer Center

Sacramento, California, 95817, United States

Location

University of California, San Francisco

San Francisco, California, 94115, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33916, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Medical College of Georgia

Augusta, Georgia, 30912, United States

Location

Central Indiana Cancer Centers

Indianapolis, Indiana, 46227, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Dana Farber Cancer Center

Boston, Massachusetts, 02115, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

University of Missouri Health Care

Columbia, Missouri, 65203, United States

Location

Kansas City Cancer Center

Lee's Summit, Missouri, 64064, United States

Location

Midwest Hematology Oncology Consultants

St Louis, Missouri, 63136, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

NYU Clinical Cancer Center

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University GYN Oncology

Hilliard, Ohio, 43026, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73190, United States

Location

Cancer Care Associates

Tulsa, Oklahoma, 74104, United States

Location

Northwest Cancer Specialists

Tualatin, Oregon, 97062, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Cancer Centers of the Carolinas, ITOR

Greenville, South Carolina, 29605, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Texas Oncology - Central Austin Cancer Center

Austin, Texas, 78731, United States

Location

Mary Crowley Medical Research Center

Dallas, Texas, 75246, United States

Location

University of Texas, M. D., Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Tyler Cancer Center

Tyler, Texas, 75702, United States

Location

Fairfax Northern Virginia Hematology Oncology

Fairfax, Virginia, 22031, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

One Study Location

Brussels, Belgium

Location

One Study Location

Jette, Belgium

Location

Multiple Study Locations

Leuven, Belgium

Location

Unknown Facility

Liège, Belgium

Location

One Study Location

Mons, Belgium

Location

One Study Location

Jerusalem, Israel

Location

One Study Location

Tel Aviv, Israel

Location

One Study Location

Tel Litwinsky, Israel

Location

One Study Location

Ẕerifin, Israel

Location

Multiple Study Locations

Tainan, Taiwan

Location

Chang Gung Medical Foundation, Taoyuan County

Taipei, Taiwan

Location

Unknown Facility

Taipei, Taiwan

Location

One Study Location

London, United Kingdom

Location

Related Publications (9)

• Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

  PMID: 37185961 DERIVED

• Schoffski P, Gordon M, Smith DC, Kurzrock R, Daud A, Vogelzang NJ, Lee Y, Scheffold C, Shapiro GI. Phase II randomised discontinuation trial of cabozantinib in patients with advanced solid tumours. Eur J Cancer. 2017 Nov;86:296-304. doi: 10.1016/j.ejca.2017.09.011. Epub 2017 Oct 20.

  PMID: 29059635 DERIVED

• Vergote IB, Smith DC, Berger R, Kurzrock R, Vogelzang NJ, Sella A, Wheler J, Lee Y, Foster PG, Weitzman R, Buckanovich RJ. A phase 2 randomised discontinuation trial of cabozantinib in patients with ovarian carcinoma. Eur J Cancer. 2017 Sep;83:229-236. doi: 10.1016/j.ejca.2017.06.018. Epub 2017 Jul 26.

  PMID: 28755607 DERIVED

• Kelley RK, Verslype C, Cohn AL, Yang TS, Su WC, Burris H, Braiteh F, Vogelzang N, Spira A, Foster P, Lee Y, Van Cutsem E. Cabozantinib in hepatocellular carcinoma: results of a phase 2 placebo-controlled randomized discontinuation study. Ann Oncol. 2017 Mar 1;28(3):528-534. doi: 10.1093/annonc/mdw651.

  PMID: 28426123 DERIVED

• Tolaney SM, Nechushtan H, Ron IG, Schoffski P, Awada A, Yasenchak CA, Laird AD, O'Keeffe B, Shapiro GI, Winer EP. Cabozantinib for metastatic breast carcinoma: results of a phase II placebo-controlled randomized discontinuation study. Breast Cancer Res Treat. 2016 Nov;160(2):305-312. doi: 10.1007/s10549-016-4001-y. Epub 2016 Oct 6.

  PMID: 27714541 DERIVED

• Leibowitz-Amit R, Pintilie M, Khoja L, Azad AA, Berger R, Laird AD, Aftab DT, Chi KN, Joshua AM. Changes in plasma biomarkers following treatment with cabozantinib in metastatic castration-resistant prostate cancer: a post hoc analysis of an extension cohort of a phase II trial. J Transl Med. 2016 Jan 13;14:12. doi: 10.1186/s12967-015-0747-y.

  PMID: 26762579 DERIVED

• Smith MR, Sweeney CJ, Corn PG, Rathkopf DE, Smith DC, Hussain M, George DJ, Higano CS, Harzstark AL, Sartor AO, Vogelzang NJ, Gordon MS, de Bono JS, Haas NB, Logothetis CJ, Elfiky A, Scheffold C, Laird AD, Schimmoller F, Basch EM, Scher HI. Cabozantinib in chemotherapy-pretreated metastatic castration-resistant prostate cancer: results of a phase II nonrandomized expansion study. J Clin Oncol. 2014 Oct 20;32(30):3391-9. doi: 10.1200/JCO.2013.54.5954. Epub 2014 Sep 15.

  PMID: 25225437 DERIVED

• Basch E, Autio KA, Smith MR, Bennett AV, Weitzman AL, Scheffold C, Sweeney C, Rathkopf DE, Smith DC, George DJ, Higano CS, Harzstark AL, Sartor AO, Gordon MS, Vogelzang NJ, de Bono JS, Haas NB, Corn PG, Schimmoller F, Scher HI. Effects of cabozantinib on pain and narcotic use in patients with castration-resistant prostate cancer: results from a phase 2 nonrandomized expansion cohort. Eur Urol. 2015 Feb;67(2):310-8. doi: 10.1016/j.eururo.2014.02.013. Epub 2014 Feb 20.

  PMID: 24631409 DERIVED

• Smith DC, Smith MR, Sweeney C, Elfiky AA, Logothetis C, Corn PG, Vogelzang NJ, Small EJ, Harzstark AL, Gordon MS, Vaishampayan UN, Haas NB, Spira AI, Lara PN Jr, Lin CC, Srinivas S, Sella A, Schoffski P, Scheffold C, Weitzman AL, Hussain M. Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial. J Clin Oncol. 2013 Feb 1;31(4):412-9. doi: 10.1200/JCO.2012.45.0494. Epub 2012 Nov 19.

  PMID: 23169517 DERIVED

MeSH Terms

Conditions

Neoplasms; Breast Neoplasms; Melanoma; Carcinoma, Hepatocellular; Small Cell Lung Carcinoma; Carcinoma, Non-Small-Cell Lung; Ovarian Neoplasms; Pancreatic Neoplasms; Prostatic Neoplasms

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Pancreatic Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Exelixis Medical Information
• Organization: Exelixis, Inc.

druginfo@exelixis.com

855-292-3935

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2009
• First Posted: July 15, 2009
• Study Start: September 1, 2009
• Primary Completion: May 1, 2013
• Study Completion: June 1, 2014
• Last Updated: April 25, 2024
• Results First Posted: April 25, 2024

Record last verified: 2023-12

Locations

BE (5); TW (3); GB (1); IL (4); US (34)