Clinical Trials /

INC280 Combined With Bevacizumab in Patients With Glioblastoma Multiforme

NCT02386826

Description:

The purpose of this study is to determine whether the combination of two agents, INC280 and bevacizumab, is safe and effective when administered to patients with Glioblastoma Multiforme (GBM) who have progressed after receiving prior therapy or who have unresectable GBM.

Related Conditions:
  • Colorectal Carcinoma
  • Glioblastoma
  • Gliosarcoma
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

INC280 Combined With <span class="go-doc-concept go-doc-intervention">Bevacizumab</span> to Evaluate <span class="go-doc-concept go-doc-disease">Glioblastoma</span> Multiforme, Metastatic <span class="go-doc-concept go-doc-disease">Colorectal Cancer</span>, and Metastatic <span class="go-doc-concept go-doc-disease">Renal Cell Carcinoma</span> Patients

Title

  • Brief Title: INC280 Combined With Bevacizumab to Evaluate Glioblastoma Multiforme, Metastatic Colorectal Cancer, and Metastatic Renal Cell Carcinoma Patients
  • Official Title: Phase Ib Study Evaluating the c-Met Inhibitor INC280 in Combination With Bevacizumab in Glioblastoma Multiforme (GBM), Metastatic Colorectal Cancer (mCRC) and Metastatic Renal Cell Carcinoma (mRCC) Patients
  • Clinical Trial IDs

    NCT ID: NCT02386826

    ORG ID: SCRI REFMAL 365

    Trial Conditions

    Glioblastoma Multiforme

    Gliosarcoma

    Colorectal Cancer

    Renal Cell Carcinoma

    Trial Interventions

    Drug Synonyms Arms
    INC280 INCB28060 INC280 with Bevacizumab

    Trial Purpose

    The purpose of this study is to determine whether the combination of two agents, INC280 and
    bevacizumab, are safe and effective when administered to patients who have received prior
    therapy for Glioblastoma Multiforme (GBM), metastatic colorectal cancer (mCRC), or
    metastatic renal cell carcinoma (mRCC) and who have progressed after therapy.

    Detailed Description

    Despite recent advances, glioblastoma multiforme (GBM) remains an incurable malignancy with
    a short expected survival. Treatment options are also limited for patients with metastatic
    colorectal cancer (mCRC) or metastatic renal cell carcinoma (mRCC) who have progressed after
    prior therapies. Novel targeted therapies are being studied to treat these patient
    populations. c-MET signalling promotes invasive growth and has been described in various
    cancers. INC280 is a highly potent and selective c-MET inhibitor which also penetrates the
    blood-brain barrier. In this open-label, multicenter Phase 1b study, investigators will
    first determine the optimal dose of INC280 combined with bevacizumab to administer as
    second-line therapy for GBM/gliosarcoma patients. After the optimal dose of the drug
    combination is determined, enrollment will be expanded to include both GBM and mRCC patients
    who have progressed after first-line therapy, and mCRC patients who have progressed as
    second-line therapy. The study will provide a preliminary safety and pharmacokinetic (PK)
    assessment of the INC280/bevacizumab combination.

    Trial Arms

    Name Type Description Interventions
    INC280 with Bevacizumab Experimental The study is divided into two phases. (1) Dose Escalation Phase: Up to 18 2nd-line GBM and gliosarcoma patients will receive bevacizumab at 10 mg/kg intravenously (IV) once every 2 weeks in combination with INC280. INC 280 will be administered orally (PO) starting at 100 mg twice daily and escalating on a 3+3 escalation pattern until the maximum tolerated dose (MTD) is determined. (2) Dose Expansion Phase: Up to 45 patients will be enrolled across 3 cohorts. Cohort A: 15 patients with 2nd-line GBM or gliosarcoma; Cohort B: 15 patients with 3rd-line mCRC; and Cohort C: 15 patients with 2nd-line mRCC. INC280 will be administered orally (PO) twice daily in each cohort at the MTD determined in the dose escalation phase. INC280 will be combined with bevacizumab administered at 10 mg/kg IV once every 2 weeks. Treatment cycles will be repeated every 28 days (4 weeks). INC280

    Eligibility Criteria

    Inclusion Criteria:

    KEY POINTS:

    1. Dose Escalation Phase: Histologic diagnosis of GBM or gliosarcoma. Progressed during
    or after standard 1st-line therapy for GBM. Patients scheduled to undergo a repeat
    primary surgical resection are also eligible. Measurable disease as measured by RANO
    (Response Assessment in Neuro-Oncology) criteria

    2. Dose Expansion Phase:

    Cohort A: Histologic diagnosis of GBM or gliosarcoma. Progressed during or after
    standard 1st-line therapy for GBM. Patients scheduled to undergo a repeat primary
    surgical resection are also eligible. Measurable disease as measured by RANO criteria

    Cohort B: Metastatic colorectal cancer (mCRC) patients after progression on
    2nd-line therapy for advanced disease. Measurable disease as measured by RECIST
    (Response Evaluation Criteria in Solid Tumors) v1.1

    Cohort C: Metastatic renal cell carcinoma (mRCC) (with clear cell component) patients
    after progression on 1st-line therapy for advanced disease. Measurable disease as
    measured by RECIST v 1.1

    At least 5 patients in each of the above 3 cohorts must have alteration of MET [as
    assessed by FISH (c-MET/centromere ratio 2, or c-MET gene copy number 5) or RT-PCR
    or Met IHC score of 2-3+ or a mutation].

    3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2 or
    Karnofsky Performance Scale (KPS) >70%

    4. Adequate hematologic, renal and liver function

    5. Life expectancy 3 months

    6. Availability of archived tumor samples and/or willingness to provide tissue samples
    if resection is done. (Fresh tissue biopsy is not required if archival tissue is not
    available.)

    Exclusion Criteria:

    1. Prior treatment with bevacizumab or any other VEGF or VEGFR inhibitors for GBM
    patients; prior treatment with bevacizumab for mRCC patients. (Prior treatment with
    bevacizumab is permitted for mCRC patients)

    2. Uncontrolled seizures (Patients with a history of seizures are eligible if they are
    currently without seizures on a stable dose of anti-epileptic drugs for 14 days prior
    to enrollment.)

    3. History of uncontrolled hereditary or acquired bleeding or thrombotic disorders.

    4. A serious non healing wound, ulcer, or bone fracture 28 days to the start of
    treatment

    5. Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89)
    administered 28 days or limited field radiation for palliation 7 days prior to
    starting study drug or has not recovered from side effects of such therapy.

    6. Leptomeningeal metastases or spinal cord compression due to disease. (mRCC and mCRC
    patients with stable treated metastases will be allowed to enroll.)

    7. Women of child-bearing potential.

    8. Receiving drugs known to be strong inhibitors or inducers of CYP3A4 and cannot be
    discontinued 7 days prior to the start of INC280 treatment and during the course of
    the study, or medications that are known CYP3A4, CYP1A2, CYP2C8, CYP2C9 or CYP2C19
    substrates with narrow therapeutic index, and cannot be discontinued during the
    course of the study.

    9. Treatment with proton pump inhibitors within three days prior to study entry.

    10. Cardiac disease currently or less than 6 months from baseline screening

    11. Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] >180 mmHg
    or diastolic blood pressure (DBP) >100 mmHg) (patients with values above these levels
    must have their blood pressure (BP) controlled with medication prior to starting
    treatment).

    12. Currently receiving treatment with therapeutic doses of warfarin sodium. Low
    molecular weight heparin is allowed.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of GBM patients with adverse events as a measure of safety and tolerability

    Secondary Outcome Measures

    Progression-free Survival

    Overall Response Rate

    Trial Keywords

    INC280

    c-MET Inhibitors

    bevacizumab

    Avastin

    C-Met proto-oncogene