Glioblastoma MultiformePhase 1NCT02386826
INC280 Combined With Bevacizumab in Patients With Glioblastoma Multiforme
A Phase 1 study testing INC280 and bevacizumab in people with Glioblastoma Multiforme and Gliosarcoma, run by SCRI Development Innovations, LLC at 5 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme, Gliosarcoma, Colorectal Cancer
- What is being tested?
- INC280 and bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 5 sitesUnited States
- Study dates
- 22 Sep 2015to 23 Aug 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- KEY POINTS:
- 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.
- Dose Expansion Phase:
- Cohort A: Histologic diagnosis of GBM. Patients should have progressed during or after standard 1st-line therapy. Patients scheduled to undergo a repeat primary surgical resection are also eligible. Measurable disease as measured by RANO criteria.
- At least 5 patients must have an alteration of MET [as assessed by fluorescence in situ hybridization (FISH) (c-MET/centromere ratio ≥2, or c-MET gene copy number ≥ 5) or RT-PCR or Met immunohistochemistry (IHC) score of 2-3+ or a mutation].
- Cohort B: Histologic diagnosis of GBM patients who have progressed during or after 2nd-line therapy with bevacizumab or a bevacizumab-based regimen. Measurable disease according to RANO criteria.
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- Cohort C: Histologic diagnosis of GBM by stereotactic biopsy in patients with unresectable brain tumors.
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2 or Karnofsky Performance Scale (KPS) of at least 70%.
- Adequate hematologic, renal and liver function
- Life expectancy ≥ 3 months
- 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.)
Who cannot join
- Prior treatment with bevacizumab for GBM patients eligible for Cohorts A and C. (Prior treatment with bevacizumab is permitted for GBM patients eligible for Cohort B only.)
- Most recent chemotherapy ≤ 21 days to the start of treatment and ≥ Grade 2 chemotherapy-related side effects with the exception of alopecia.
- Use of any investigational drug ≤ 21 days to the start of treatment or 5 half-lives (whichever is shorter) prior to the first dose of INC280 with bevacizumab. For study drugs for which 5 half-lives is ≤ 21 days, a minimum of 10 days between termination of the study drug and the start of treatment is required.
- 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.)
- History of uncontrolled hereditary or acquired bleeding or thrombotic disorders.
- Major surgery ≤ 28 days to the start of treatment, or subcutaneous venous access device placement ≤ 7 days to the start of treatment
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- A serious non healing wound, ulcer, or bone fracture ≤ 28 days to the start of treatment
- 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.
- Leptomeningeal metastases or spinal cord compression due to disease.
- Women of child-bearing potential.
- 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.
- Treatment with proton pump inhibitors within three days prior to study entry.
- Cardiac disease currently or less than 6 months from baseline screening
- 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).
- Currently receiving treatment with therapeutic doses of warfarin sodium. Low molecular weight heparin is allowed.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, 80218
HCA Midwest - Kansas City
Kansas City, Missouri, 64132
Tennessee Oncology PLLC
Nashville, Tennessee, 37203
Yale School of Medicine
New Haven, Connecticut, 06520
Oklahoma University Health Science Center
Oklahoma City, Oklahoma, 73104
About this study
Official title: Phase Ib Study Evaluating the c-Met Inhibitor INC280 in Combination With Bevacizumab in Patients With Glioblastoma Multiforme (GBM)
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.
Read the detailed description
Despite recent advances, glioblastoma multiforme (GBM) remains an incurable malignancy with a short expected survival. 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 determined the optimal dose of the INC280/bevacizumab combination to administer to patients. Enrollment has now expanded in order to treat 3 cohorts of GBM patients: those who progressed after ≥ first-line standard therapy, those who progressed after ≥ second-line therapy with INC280/bevacizumab, and those with unresectable GBM.
- Being tested
- INC280, bevacizumab
- Keywords
- INC280, c-MET Inhibitors, bevacizumab, Avastin, C-Met proto-oncogene
- Medical subject headings
- Glioblastoma, Gliosarcoma, Colorectal Neoplasms, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INC280Drug
Also called INCB28060
Dose Escalation: INC280 by mouth (PO) twice daily for 28 days according to the following schedule until the maximum tolerated dose (MTD) is determined:
Dose Level 1 (starting dose): 200 mg (divided dose of 100 mg twice per day) Dose Level 2: 400 mg (divided dose of 200 mg twice per day) Dose Level 3: 800 mg (divided dose of 400 mg twice per day)
Dose Expansion: INC280 PO twice daily at the MTD determined in the dose escalation phase
bevacizumabBiological
Also called Avastin
bevacizumab: 10 mg/kg IV every 2 weeks. Patients with unresectable GBM will be given 15 mg/kg IV every 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| INC280 + Bevacizumab | Experimental | 1. Dose Escalation: 18 GBM patients received bevacizumab 10 mg/kg intravenously (IV) once every 2 weeks in combination with INC280 given by mouth (PO) starting at 100 mg twice daily and escalating on a 3+3 escalation pattern until the maximum tolerated dose (MTD) was determined.
2. Dose Expansion: Up to 45 GBM patients enrolled in 3 Cohorts:
Cohort A: 20 GBM patients - progressed during or after standard 1st-line therapy; Cohort B: 15 GBM patients - progressed during or after 2nd-line bevacizumab therapy; Cohort C: 10 unresectable GBM patients.
INC280: PO twice daily at the MTD. Bevacizumab: 10 mg/kg IV once every 2 weeks for Cohorts A and B; 15 mg/kg IV every 4 weeks for Cohort C Treatment cycles will be repeated every 28 days (4 weeks). Receives: Drug: INC280; Biological: bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of INC280
The MTD of INC280 to be administered with standard dose bevacizumab is determined as the highest dose at which ≤1 of 6 patients experiences a dose limiting toxicity (DLT) during one cycle (28 days) of therapy, assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v. 4.0.3
Measured: weekly for 4 weeks
Secondary outcomes (2)
Progression-free Survival
Progression-free survival is measured from Day 1 of study drug administration to disease progression or death on study. Disease progression is assessed by Response Assessment in Neuro-Oncology (RANO) criteria.
Measured: every 8 weeks until treatment discontinuation, expected average of 6 months
Overall Response Rate
Defined as the proportion of patients with confirmed complete response or partial response (CR or PR) assessed according to RANO criteria. CR=complete disappearance of all measurable and non-measurable disease sustained for at least 4 weeks. PR=≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks.
Measured: Every 8 weeks up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2015 (estimated)
- Study start22 Sep 2015
- Primary completion31 Jul 2021
- Study completion23 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Kent C. Shih, M.D., Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02386826
- Sponsor's protocol ID
- SCRI REFMAL 365
- Status last verified
- Sep 2023
- First submitted
- 6 Mar 2015
- Last updated
- 21 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Study Evaluating the c-Met Inhibitor INC280 in Combination With Bevacizumab in Patients With Glioblastoma Multiforme (GBM)
- ClinicalTrials.gov ID
- NCT02386826
- Acronym / sponsor ID
- SCRI REFMAL 365
- Keywords
- INC280, c-MET Inhibitors, bevacizumab, Avastin, C-Met proto-oncogene
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- 22 Sep 2015 (actual)
- Primary completion
- 31 Jul 2021 (actual)
- Study completion
- 23 Aug 2023 (actual)
- First posted
- 12 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Despite recent advances, glioblastoma multiforme (GBM) remains an incurable malignancy with a short expected survival. 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 determined the optimal dose of the INC280/bevacizumab combination to administer to patients. Enrollment has now expanded in order to treat 3 cohorts of GBM patients: those who progressed after ≥ first-line standard therapy, those who progressed after ≥ second-line therapy with INC280/bevacizumab, and those with unresectable GBM.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| INC280 + Bevacizumab | Experimental | Drug: INC280, Biological: bevacizumab1. Dose Escalation: 18 GBM patients received bevacizumab 10 mg/kg intravenously (IV) once every 2 weeks in combination with INC280 given by mouth (PO) starting at 100 mg twice daily and escalating on a 3+3 escalation pattern until the maximum tolerated dose (MTD) was determined. 2. Dose Expansion: Up to 45 GBM patients enrolled in 3 Cohorts: Cohort A: 20 GBM patients - progressed during or after standard 1st-line therapy; Cohort B: 15 GBM patients - progressed during or after 2nd-line bevacizumab therapy; Cohort C: 10 unresectable GBM patients. INC280: PO twice daily at the MTD. Bevacizumab: 10 mg/kg IV once every 2 weeks for Cohorts A and B; 15 mg/kg IV every 4 weeks for Cohort C Treatment cycles will be repeated every 28 days (4 weeks). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
- Dose Expansion Phase:
- Cohort A: Histologic diagnosis of GBM. Patients should have progressed during or after standard 1st-line therapy. Patients scheduled to undergo a repeat primary surgical resection are also eligible. Measurable disease as measured by RANO criteria.
- At least 5 patients must have an alteration of MET [as assessed by fluorescence in situ hybridization (FISH) (c-MET/centromere ratio ≥2, or c-MET gene copy number ≥ 5) or RT-PCR or Met immunohistochemistry (IHC) score of 2-3+ or a mutation].
- Cohort B: Histologic diagnosis of GBM patients who have progressed during or after 2nd-line therapy with bevacizumab or a bevacizumab-based regimen. Measurable disease according to RANO criteria.
Key exclusion criteria (15 listed)
- Prior treatment with bevacizumab for GBM patients eligible for Cohorts A and C. (Prior treatment with bevacizumab is permitted for GBM patients eligible for Cohort B only.)
- Most recent chemotherapy ≤ 21 days to the start of treatment and ≥ Grade 2 chemotherapy-related side effects with the exception of alopecia.
- Use of any investigational drug ≤ 21 days to the start of treatment or 5 half-lives (whichever is shorter) prior to the first dose of INC280 with bevacizumab. For study drugs for which 5 half-lives is ≤ 21 days, a minimum of 10 days between termination of the study drug and the start of treatment is required.
- 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.)
- History of uncontrolled hereditary or acquired bleeding or thrombotic disorders.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INC280Also: INCB28060Dose Escalation: INC280 by mouth (PO) twice daily for 28 days according to the following schedule until the maximum tolerated dose (MTD) is determined: Dose Level 1 (starting dose): 200 mg (divided dose of 100 mg twice per day) Dose Level 2: 400 mg (divided dose of 200 mg twice per day) Dose Level 3: 800 mg (divided dose of 400 mg twice per day) Dose Expansion: INC280 PO twice daily at the MTD determined in the dose escalation phase | Drug | INC280 + Bevacizumab |
| bevacizumabAlso: Avastinbevacizumab: 10 mg/kg IV every 2 weeks. Patients with unresectable GBM will be given 15 mg/kg IV every 4 weeks. | Biological | INC280 + Bevacizumab |
Primary outcome
Maximum Tolerated Dose (MTD) of INC280
Time frame: weekly for 4 weeks
The MTD of INC280 to be administered with standard dose bevacizumab is determined as the highest dose at which ≤1 of 6 patients experiences a dose limiting toxicity (DLT) during one cycle (28 days) of therapy, assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v. 4.0.3
2 secondary outcomes
Progression-free Survival
Time frame: every 8 weeks until treatment discontinuation, expected average of 6 months
Overall Response Rate
Time frame: Every 8 weeks up to 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kent C. Shih, M.D. study chair
SCRI Development Innovations, LLC
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing INC280 and bevacizumab in people with Glioblastoma Multiforme and Gliosarcoma, run by SCRI Development Innovations, LLC at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of INC280 (time frame: weekly for 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2023.