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NCT00940225 · REGISTRY CONDITION SEARCH

Study of Cabozantinib (XL184) in Adults With Advanced Malignancies

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2024-04-25

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

Bone Scan Response (BSR) - NRE, CRPC

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Progression Free Survival (PFS) - Throughout the Study

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outcome · POSTED

Duration of Bone Scan Response - NRE Cohorts, CRPC Only

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: * 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 * 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 Exclusion Criteria: * 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
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Open Label, cabozantinib, 100 mg, po QD for 12 weeks.
    intervention Names
    1. Drug: Cabozantinib
    label
    Lead-in Stage - cabozantinib (XL184)
    type
    EXPERIMENTAL
  2. description
    Blinded, cabozantinib, 100 mg, po QD until disease progression.
    intervention Names
    1. Drug: Cabozantinib
    label
    Randomized Stage - cabozantinib (XL184)
    type
    EXPERIMENTAL
  3. description
    Blinded, placebo, 100 mg, po QD until disease progression.
    intervention Names
    1. Drug: Placebo
    label
    Randomized Stage - placebo
    type
    PLACEBO_COMPARATOR
  4. description
    Open Label, cabozantinib, for subjects that were on placebo during the randomized stage, 100 mg, po QD until disease progression or unacceptable toxicity.
    intervention Names
    1. Drug: Cabozantinib
    label
    Open-Label Extension - cabozantinib (XL184)
    type
    EXPERIMENTAL
  5. description
    Open Label, cabozantinib, 100 mg, po QD until disease progression or unacceptable toxicity.
    intervention Names
    1. Drug: Cabozantinib
    label
    Non-Randomized Expansion (NRE) Cohort - Castrate Resistant Prostate Cancer (CRPC), 100mg
    type
    EXPERIMENTAL
  6. description
    Open Label, cabozantinib, 39.4, po QD until disease progression or unacceptable toxicity.
    intervention Names
    1. Drug: Cabozantinib
    label
    Non-Randomized Expansion (NRE) Cohort - Castrate Resistant Prostate Cancer (CRPC), 39.4mg
    type
    EXPERIMENTAL
  7. description
    Open Label, cabozantinib, 100 mg, po QD until disease progression or unacceptable toxicity.
    intervention Names
    1. Drug: Cabozantinib
    label
    A. Non-Randomized Expansion (NRE) Cohort - Ovarian
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. A. Non-Randomized Expansion (NRE) Cohort - Ovarian
    2. Lead-in Stage - cabozantinib (XL184)
    3. Non-Randomized Expansion (NRE) Cohort - Castrate Resistant Prostate Cancer (CRPC), 100mg
    4. Non-Randomized Expansion (NRE) Cohort - Castrate Resistant Prostate Cancer (CRPC), 39.4mg
    5. Open-Label Extension - cabozantinib (XL184)
    6. Randomized Stage - cabozantinib (XL184)
    name
    Cabozantinib
    other Names
    1. XL184
    type
    DRUG
  2. arm Group Labels
    1. Randomized Stage - placebo
    name
    Placebo
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
SEQUENTIAL
masking Info
masking
QUADRUPLE
who Masked
  1. PARTICIPANT
  2. CARE_PROVIDER
  3. INVESTIGATOR
  4. OUTCOMES_ASSESSOR
primary Purpose
TREATMENT
Enrollment
count
730
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    Objective Response Rate (ORR) - LEAD IN STAGE, RDT Cohorts and NRE Ovarian Cohort Only
    time Frame
    From initial dose through final study visit up to 44 months
  2. description
    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.
    measure
    Bone Scan Response (BSR) - NRE, CRPC
    time Frame
    From initial dose through final study visit up to 15 months
  3. description
    Progression Free Survival during the Randomized Stage (Randomized Population)
    measure
    Progression-Free Survival (PFS) - Randomized Stage, RDT Cohorts Only
    time Frame
    From initial dose through final study visit up to 44 months
secondary Outcomes
  1. description
    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.
    measure
    Duration of Objective Response (OR) - Responders From Lead-in Stage
    time Frame
    From initial dose through final study visit up to 44 months
  2. description
    Progression-free survival (PFS) from first dose throughout the study was estimated for all subjects (safety population) using a piecewise method.
    measure
    Progression Free Survival (PFS) - Throughout the Study
    time Frame
    From initial dose through final study visit up to 44 months
  3. description
    The duration of BSR per IRF was calculated for CRPC subjects with an objective response (CR or PR) during the study.
    measure
    Duration of Bone Scan Response - NRE Cohorts, CRPC Only
    time Frame
    From initial dose through final study visit up to 15 months
  4. measure
    Overall Survival (OS) - NRE Cohorts, CRPC and Ovarian Only
    time Frame
    From initial dose through final study visit up to 15 months
Full study description
brief Summary
This is a Phase 2 study to evaluate the efficacy and safety of cabozantinib (XL184) in subjects with selected advanced tumor types.
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): 1. 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. 2. 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. 3. 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.
Source references
references
  1. citation
    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
    type
    DERIVED
  2. citation
    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
    type
    DERIVED
  3. citation
    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
    type
    DERIVED
  4. citation
    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
    type
    DERIVED
  5. citation
    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
    type
    DERIVED
  6. citation
    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
    type
    DERIVED
  7. citation
    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
    type
    DERIVED
  8. citation
    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
    type
    DERIVED
  9. citation
    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
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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    Preserved source evidence · Not medical advice