Glioblastoma MultiformePhase 2NCT00704288
Study of XL184 (Cabozantinib) in Adults With Glioblastoma Multiforme
A Phase 2 study testing XL184 in people with Glioblastoma Multiforme, run by Exelixis at 8 sites in United States.
Trial summary
The purpose of this study is to evaluate the objective response rate and 6-month progression-free survival rate of XL184 in subjects with recurrent or progressive glioblastoma multiforme. XL184 is a new chemical entity that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- XL184
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 222 participants
- Where
- 8 sitesUnited States
- Study dates
- May 2008to Dec 2012
- 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 locally determined histologically confirmed diagnosis of Grade 4 astrocytic tumor.
- The subject has received prior standard radiation for Grade 3 or 4 astrocytic tumor.
- The subject has received prior temozolomide therapy for Grade 3 or 4 astrocytic tumor (if in first relapse, the subject must have received temozolomide until progression, intolerance, or completion of planned therapy; if in second relapse, the subject must have received temozolomide until progression, intolerance, or completion of planned therapy either for first-line treatment or for treatment after first relapse).
- The subject is in first or second Grade 4 relapse, defined as having one or two progressions as Grade 4 astrocytic tumor since the original diagnosis of any grade glioma.
- The subject must have a baseline brain MRI scan within 14 days prior to first dose of XL184 while either not receiving glucocorticoids during the 5 days prior to the baseline MRI scan or on a stable dose of glucocorticoids during the 5 days prior to the baseline MRI scan.
- Subjects having undergone recent resection or biopsy of tumor will be eligible as long as all of the following conditions apply: First dose of XL184 occurs at least 28 days after surgery, the subject has recovered from the effects of surgery, and the subject has measurable residual disease.
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- The subject is at least 18 years old.
- The subject has a KPS (Karnofsky Performance Scale) of ≥ 70%.
- The subject is capable of understanding the protocol and has signed the informed consent document.
- The subject has adequate organ and marrow function.
- Sexually active subjects (male and female) must agree to use medically accepted methods of contraception during the course of the study and for 3 months following discontinuation of study drug.
- Female subjects of childbearing potential must have a negative pregnancy test at enrollment.
Who cannot join
- The subject has received non-standard radiation therapy for glioblastoma, non-anti-angiogenic therapy (including investigational agents, small-molecule kinase inhibitors, and biologic agents) or non-cytotoxic hormonal agent within 28 days of the first scheduled dose of XL184 or mitomycin C within 42 days of the first scheduled dose of XL184, other investigational therapy (including agents not specified above) within 28 days of the first scheduled dose of XL184, or prior treatment with nitrosoureas (including carmustine wafer) at any time.
- Some subjects may not have had any prior VEGF- or VEGFR2-based anti-angiogenic therapy (such as bevacizumab, cediranib, or pazopanib).
- Some subjects may not have had bevacizumab within 14 days of the first scheduled dose of XL184.
- The subject is receiving warfarin (or other coumarin derivatives) at study entry and unable to switch to low molecular weight heparin.
- The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin may enter the study.
- The subject is unable to undergo MRI scan (eg, has pacemaker).
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- The subject has received enzyme-inducing anti-epileptic agents within 2 weeks before the first dose of XL184 (eg, carbamazepine, phenytoin, phenobarbital, primidone).
- The subject has not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade ≤ 1 from adverse events (AEs) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered before study enrollment.
- The subject has evidence of wound dehiscence.
- The subject is pregnant or breast-feeding.
- The subject has serious intercurrent illness, such as uncontrolled hypertension, unhealed wounds from recent surgery or cardiac arrhythmias or a recent history of significant disease such as either symptomatic congestive heart failure or unstable angina pectoris within the past 3 months, myocardial infarction within the past 6 months, or active infection requiring systemic treatment/hospitalization within 2 weeks of the first scheduled dose of XL184
- The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding.
- The subject has received any live virus vaccine within 28 days or any inactivated vaccine within 7 days prior to first dose of XL184.
- The subject has had another diagnosis of malignancy (unless nonmelanoma skin cancer, in situ carcinoma of the cervix, or a malignancy diagnosed ≥ 2 years previously) or currently has evidence of malignancy (unless non-melanoma skin cancer or in situ carcinoma of the cervix).
- The subject has a known allergy or hypersensitivity to any of the components of the XL184 formulations.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
University of Virginia Health System
Charlottesville, Virginia, 22908
Henry Ford Health System
Detroit, Michigan, 48202
Duke University, The Preston Robert Tisch Brain Tumor Center
Durham, North Carolina, 27710
University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030
University of California, Los Angeles
Los Angeles, California, 90095
University of California, San Francisco
San Francisco, California, 94143
University of Washington
Seattle, Washington, 98195
About this study
Official title: A Phase 2 Study of XL184 in Subjects With Progressive or Recurrent Glioblastoma Multiforme in First or Second Relapse
The purpose of this study is to evaluate the objective response rate and 6-month progression-free survival rate of XL184 in subjects with recurrent or progressive glioblastoma multiforme. XL184 is a new chemical entity that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration.
- Conditions
- Glioblastoma Multiforme
- Being tested
- XL184
- Keywords
- GBM, Malignant gliomas
- Medical subject headings
- Glioblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XL184Drug
Gelatin capsules supplied in 25-mg and 100-mg strengths; continuous daily dosing
| Study group | Role | What they receive |
|---|---|---|
| Group A cabozantinib 175 mg | Experimental | cabozantinib, 175 mg, taken orally once per day (qd). Receives: Drug: XL184 |
| Group B cabozantinib 125 mg | Experimental | cabozantinib, 125 mg, taken orally once per day (qd). Receives: Drug: XL184 |
| Group C 125 mg | Experimental | cabozantinib, 125 mg, taken orally once per day (qd). Receives: Drug: XL184 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
Response and progression were determined per modified MacDonald Criteria and modified RANO criteria for GBM using imaging and clinical features
Measured: 8 weeks until progressive disease
Secondary outcomes (3)
Duration of Objective Response (Months)
Duration of response is defined as the time from the first documentation of objective response that was subsequently confirmed at a visit that was ≥ 28 days later to disease progression or death due to any cause.
Measured: Assessed during periodically scheduled visits until progressive disease
Progression Free Survival (PFS)
Response and progression were determined per modified MacDonald Criteria and modified RANO criteria for GBM using imaging and clinical features
Measured: Assessed during periodically scheduled visits until progressive disease
Overall Survival (OS)
Overall survival (OS) is defined as the time from first dose to death due to any cause.
Measured: Assessed during periodically scheduled visits until progressive disease
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2008 (estimated)
- Study startMay 2008
- Primary completionJun 2012
- Study completionDec 2012
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 (5)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 222 participants (actual)
Sponsor and investigators
- Lead sponsor
- Exelixis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00704288
- Sponsor's protocol ID
- XL184-201
- Status last verified
- Jan 2024
- First submitted
- 20 Jun 2008
- Last updated
- 5 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Ellingson BM, Hagiwara A, Morris CJ, Cho NS, Oshima S, Sanvito F, Oughourlian TC, Telesca D, Raymond C, Abrey LE, Garcia J, Aftab DT, Hessel C, Rachmilewitz Minei T, Harats D, Nathanson DA, Wen PY, Cloughesy TF. Depth of Radiographic Response and Time to Tumor Regrowth Predicts Overall Survival Following Anti-VEGF Therapy in Recurrent Glioblastoma. Clin Cancer Res. 2023 Oct 13;29(20):4186-4195. doi: 10.1158/1078-0432.CCR-23-1235.
PubMed 37540556Ellingson BM, Aftab DT, Schwab GM, Hessel C, Harris RJ, Woodworth DC, Leu K, Chakhoyan A, Raymond C, Drappatz J, de Groot J, Prados MD, Reardon DA, Schiff D, Chamberlain M, Mikkelsen T, Desjardins A, Holland J, Ping J, Weitzman R, Wen PY, Cloughesy TF. Volumetric response quantified using T1 subtraction predicts long-term survival benefit from cabozantinib monotherapy in recurrent glioblastoma. Neuro Oncol. 2018 Sep 3;20(10):1411-1418. doi: 10.1093/neuonc/noy054.
PubMed 29660005Cloughesy TF, Drappatz J, de Groot J, Prados MD, Reardon DA, Schiff D, Chamberlain M, Mikkelsen T, Desjardins A, Ping J, Holland J, Weitzman R, Wen PY. Phase II study of cabozantinib in patients with progressive glioblastoma: subset analysis of patients with prior antiangiogenic therapy. Neuro Oncol. 2018 Jan 22;20(2):259-267. doi: 10.1093/neuonc/nox151.
PubMed 29036345Wen PY, Drappatz J, de Groot J, Prados MD, Reardon DA, Schiff D, Chamberlain M, Mikkelsen T, Desjardins A, Holland J, Ping J, Weitzman R, Cloughesy TF. Phase II study of cabozantinib in patients with progressive glioblastoma: subset analysis of patients naive to antiangiogenic therapy. Neuro Oncol. 2018 Jan 22;20(2):249-258. doi: 10.1093/neuonc/nox154.
PubMed 29016998Ellingson BM, Harris RJ, Woodworth DC, Leu K, Zaw O, Mason WP, Sahebjam S, Abrey LE, Aftab DT, Schwab GM, Hessel C, Lai A, Nghiemphu PL, Pope WB, Wen PY, Cloughesy TF. Baseline pretreatment contrast enhancing tumor volume including central necrosis is a prognostic factor in recurrent glioblastoma: evidence from single and multicenter trials. Neuro Oncol. 2017 Jan;19(1):89-98. doi: 10.1093/neuonc/now187. Epub 2016 Aug 31.
PubMed 27580889