Solid TumorsPhase 2NCT00940225
Study of Cabozantinib (XL184) in Adults With Advanced Malignancies
A Phase 2 study testing Cabozantinib in people with Solid Tumors and Cancer, run by Exelixis at 47 sites in 5 countries.
Trial summary
This is a Phase 2 study to evaluate the efficacy and safety of cabozantinib (XL184) in subjects with selected advanced tumor types. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Cancer
- What is being tested?
- Cabozantinib
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 730 participants
- Where
- 47 sitesin 5 countries
- Study dates
- Sep 2009to Jun 2014
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Tissue samples from archival or fresh tissue, or a tissue block of the subject's tumor
- The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- The subject has adequate organ function
- The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document
- Sexually active fertile subjects (male and female), and their partners, must agree to use medically accepted methods of contraception during the course of the study and for 3 months after the last dose of the study drug(s)
- Female subjects of childbearing potential must have a negative pregnancy test at screening
Who cannot join
- 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)
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- 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
Trial locations and contacts
47 sites in 5 countries.
47 sites in 5 countries
United States34 sites
University of Michigan Health System
Ann Arbor, Michigan, 48109
Medical College of Georgia
Augusta, Georgia, 30912
Texas Oncology - Central Austin Cancer Center
Austin, Texas, 78731
Dana Farber Cancer Center
Boston, Massachusetts, 02115
University of Missouri Health Care
Columbia, Missouri, 65203
Mary Crowley Medical Research Center
Dallas, Texas, 75246
Rocky Mountain Cancer Centers
Denver, Colorado, 80218
Wayne State University
Detroit, Michigan, 48201
Duke University Medical Center
Durham, North Carolina, 27710
Fairfax Northern Virginia Hematology Oncology
Fairfax, Virginia, 22031
Florida Cancer Specialists
Fort Myers, Florida, 33916
Cancer Centers of the Carolinas, ITOR
Greenville, South Carolina, 29605
Ohio State University GYN Oncology
Hilliard, Ohio, 43026
University of Texas, M. D., Anderson Cancer Center
Houston, Texas, 77030
Central Indiana Cancer Centers
Indianapolis, Indiana, 46227
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
Kansas City Cancer Center
Lee's Summit, Missouri, 64064
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, 33140
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Yale University School of Medicine
New Haven, Connecticut, 06520
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112
NYU Clinical Cancer Center
New York, New York, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Oklahoma
Oklahoma City, Oklahoma, 73190
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of California Davis Cancer Center
Sacramento, California, 95817
University of California, San Francisco
San Francisco, California, 94115
Pinnacle Oncology of Arizona
Scottsdale, Arizona, 85258
University of Washington
Seattle, Washington, 98109
Midwest Hematology Oncology Consultants
St Louis, Missouri, 63136
Stanford University Medical Center
Stanford, California, 94305
Northwest Cancer Specialists
Tualatin, Oregon, 97062
Cancer Care Associates
Tulsa, Oklahoma, 74104
Tyler Cancer Center
Tyler, Texas, 75702
Belgium5 sites
One Study Location
Brussels
One Study Location
Jette
Multiple Study Locations
Leuven
Study site
Liège
One Study Location
Mons
Israel4 sites
One Study Location
Jerusalem
One Study Location
Tel Aviv
One Study Location
Tel Litwinsky
One Study Location
Ẕerifin
Taiwan3 sites
Multiple Study Locations
Tainan
Chang Gung Medical Foundation, Taoyuan County
Taipei
Study site
Taipei
About this study
Official title: A Randomized Discontinuation Study of XL184 in Subjects With Advanced Solid Tumors
This is a Phase 2 study to evaluate the efficacy and safety of cabozantinib (XL184) in subjects with selected advanced tumor types.
Read the detailed description
The goal of this clinical trial was to learn about the efficacy, safety, and tolerability of cabozantinib against a placebo in subjects with Metastatic Breast Cancer (MBC), Gastric and Gastroesophageal Junction Cancer (GEJ), Hepatocellular Carcinoma (HCC), Melanoma, Non-small Cell Lung Cancer (NSCLC), Ovarian (primary peritoneal or fallopian tube carcinoma), Pancreatic Cancer, Castration-Resistant Prostate Cancer (CRPC), or Small cell Lung Cancer (SCLC) with advanced tumors.
The main questions this study aimed to answer were:
- What is the efficacy of cabozantinib in subjects with advanced solid tumors?
- What is the safety and efficacy of cabozantinib at two starting dose levels 100 milligrams (mg) once daily (po QD) and 39.4 mg po QD? Please note: that the 39.4 mg, po QD was only used in the Non-Randomized Expansion (NRE) part of the study
There were three stages to the Randomized Discontinuation Trial (RDT):
- The Lead in Stage: This stage enrolled eligible patients with advanced solid tumors who received open-label cabozantinib at 100 mg once daily for 12 weeks.
- The Randomized Stage: Subjects who demonstrated stable disease (SD) at the end of 12 weeks of the Lead-in Stage were randomized to receive cabozantinib or placebo (a look-alike substance that contains no active drug) in a blinded manner. After randomization, when a patient developed progressive disease (PD), study treatments were discontinued and the treatment blind was broken. If the subject was on a placebo, the subject was offered the opportunity to receive cabozantinib. If the subject was already on cabozantinib, the subject entered the Post-Treatment Period where they were followed until death.
- Open-Label Extension: Subjects who were deemed with partial response (PR) or complete response (CR) at Week 12 of the Lead-In Stage were not randomized but allowed to participate in the "Open Label Extension". Patients were given the cabozantinib treatment of 100 mg, po QD.
The emerging data supported enrollment in an open-label, Non-Randomized Expansion cohort (NRE). These cohorts targeted patients with prostate and ovarian cancers. For the patients with prostate, they were assigned to either 100 mg, po QD or 39.4 mg, po QD.
- Conditions
- Solid Tumors, Cancer
- Being tested
- Cabozantinib, Placebo
- 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
- Medical subject headings
- Neoplasms, Breast Neoplasms, Melanoma, Carcinoma, Hepatocellular, Small Cell Lung Carcinoma, Carcinoma, Non-Small-Cell Lung, Ovarian Neoplasms, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabozantinibDrug
Also called XL184
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Lead-in Stage - cabozantinib (XL184) | Experimental | Open Label, cabozantinib, 100 mg, po QD for 12 weeks. Receives: Drug: Cabozantinib |
| Randomized Stage - cabozantinib (XL184) | Experimental | Blinded, cabozantinib, 100 mg, po QD until disease progression. Receives: Drug: Cabozantinib |
| Randomized Stage - placebo | Placebo comparator | Blinded, placebo, 100 mg, po QD until disease progression. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Cabozantinib |
| A. Non-Randomized Expansion (NRE) Cohort - Ovarian | Experimental | Open Label, cabozantinib, 100 mg, po QD until disease progression or unacceptable toxicity. Receives: Drug: Cabozantinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
Measured: From initial dose through final study visit up to 44 months
Secondary outcomes (4)
Duration of Objective Response (OR) - Responders From Lead-in Stage
Duration of objective response was defined as the time from the tumor assessment that first documented PR or CR that was subsequently confirmed at least 28 days later until the date of documented progression. There were either few or no responders in the Gastric/GEJ, SCLC, and pancreatic cohorts so these cohorts are excluded.
Measured: From initial dose through final study visit up to 44 months
Progression Free Survival (PFS) - Throughout the Study
Progression-free survival (PFS) from first dose throughout the study was estimated for all subjects (safety population) using a piecewise method.
Measured: From initial dose through final study visit up to 44 months
Duration of Bone Scan Response - NRE Cohorts, CRPC Only
The duration of BSR per IRF was calculated for CRPC subjects with an objective response (CR or PR) during the study.
Measured: From initial dose through final study visit up to 15 months
Overall Survival (OS) - NRE Cohorts, CRPC and Ovarian Only
Measured: From initial dose through final study visit up to 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2009 (estimated)
- Study startSep 2009
- Primary completionMay 2013
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by ExelixisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 730 participants (actual)
Sponsor and investigators
- Lead sponsor
- Exelixis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00940225
- Sponsor's protocol ID
- XL184-203
- Status last verified
- Dec 2023
- First submitted
- 12 Jul 2009
- Last updated
- 25 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 37185961Schoffski 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.
PubMed 29059635Vergote 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.
PubMed 28755607Kelley 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.
PubMed 28426123Tolaney 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.
PubMed 27714541Leibowitz-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.
PubMed 26762579Smith 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.
PubMed 25225437Basch 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.
PubMed 24631409Smith 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.
PubMed 23169517