Glioblastoma MultiformePhase 2NCT02885324
Pilot Study of Cabozantinib for Recurrent or Progressive Central Nervous System Tumors in Children
A Phase 2 study testing Cabozantinib in people with Glioblastoma Multiforme and Anaplastic Astrocytoma, run by Indiana University at 1 site in United States.
Trial summary
This pilot will study the feasibility and exploratory efficacy of using Cabozantinib for recurrent or refractory central nervous system tumors for which there are no curative options. Patients will also be followed for safety, time to progression, event free survival and overall survival Read more about this study
- Who is it for?
- Ages 2 to 21 years
- Conditions the study is for
- Glioblastoma Multiforme, Anaplastic Astrocytoma, Malignant Brain Tumor
- What is being tested?
- Cabozantinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 18 May 2017to 25 Aug 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 2 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: Patients must be ≥2 years and ≤21 years of age
- Diagnosis: Patients with relapsed or refractory central nervous system tumors. Patients must have had histological verification of malignancy at original diagnosis or relapse. Metastatic disease to the spine or primary tumors in the spine are eligible. Patients may be in first, second, or third relapse. Subjects with intrinsic brain stem gliomas may be eligible with or without histological confirmation. Please contact study chair prior to enrollment.
- Disease Status: Patients must have measurable disease. Linear enhancement of leptomeningeal without measurable mass is excluded.
- Therapeutic Options: Patient's current disease state must be one for which there is no accepted standard therapy, no known curative therapy or therapy proven to prolong survival with an acceptable quality of life. For patients in whom surgery is feasible, maximal surgical resection must have occurred.
- Performance Level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix 1). Note: Neurologic deficits in patients must have been relatively stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Subjects must have a reasonable life expectancy of at least 2 months.
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- Prior Therapy
- Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy i. Cytotoxic chemotherapy (including investigational agents) or biologic agents (eg. Cytokines or antibodies): At least 3 weeks after the last dose.
- Nitrosoureas/mitomycin C: At least 6 weeks from the last dose. iii. XRT: At least 14 days after local palliative XRT (small port); At least 150 days must have elapsed if prior TBI, craniospinal XRT or if ≥ 50% radiation of pelvis; At least 42 days must have elapsed if other substantial BM radiation. e.g. Stem cell Infusion without TBI: No evidence of active graft vs. host disease and at least 56 days must have elapsed after transplant or stem cell infusion.
- Organ Function Requirements:
- Adequate bone marrow function defined as: absolute neutrophil count (ANC ≥1000/mm3) i. Platelet count ≥ 100,000/ mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) ii. Patients with bone marrow metastatic disease will not be eligible. b. Adequate renal function defined as: i. Creatinine clearance or radioisotope GFR ≥ 70mL/min/1.73 m² or a serum creatinine based on age/gender as follows:
- Age Maximum Serum Creatinine (mg/dL) Male Female 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4
- ≥ 16 years 1.7 1.4 The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.
- Urine protein: ≤ 30 mg/dL in urinalysis or ≤ 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 hour urine sample.
- Adequate Liver Function Defined as:
- Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age ii. SGPT (ALT) ≤ 110 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
- Serum albumin ≥ 2.8 g/dL. d. Adequate coagulation status defined as: PT and INR ≤ 1.5x ULN e. Adequate pancreatic function defined as: Serum amylase and lipase ≤ 1.5 x ULN f. Adequate blood pressure control defined as: A blood pressure (BP) ≤ the 95th percentile for age, height and gender (Appendix II) despite optimal antihypertensive treatment within 7 days of the first dose of the study treatment. Please note that 3 serial blood pressures should be obtained and averaged to determine baseline BP.
- Central nervous system function defined as: Patients with seizure disorder may be enrolled if receiving non-enzyme inducing anticonvulsants and well controlled. See Appendix III for a list of recommended non-enzyme inducing anticonvulsants.
- Adequate cardiac function defined as: i. No history of congenital QTc syndrome, NYHA Class III or IV congestive heart failure (CHF) ii. No clinical significant cardiac arrhythmias, stroke or myocardial infarction within 6 months prior to enrollment iii. QTc
- ≤ 480 msec. Note: One ECG must be performed for eligibility determination. If the QTc is > 480 msec, two additional ECGs must be performed and the average of the three ECGs will be used to determine eligibility. Patients with Grade 1 prolonged QTc (450-480 msec) at the time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e. electrolytes, medications). See Appendix IV for a list of drugs that prolong QTc.
- Informed consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate will be obtained according to institutional guidelines.
- Archival tumor tissue slides must be sent or available, except for patients with intrinsic pontine glioma meeting the remainder of the inclusion criteria.
Who cannot join
- Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogentic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two methods of birth control- a medically accepted barrier method of contraceptive method (e.g., male or female condom) and a second effective method of birth control- during protocol therapy and for at least 4 months after the last dose of cabozantinib. Abstinence is an acceptable method of birth control.
- Concomitant Medications:
- Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible.
- Investigational drugs: Patients who are currently receiving another investigational drug are not eligible.
- Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible.
- CYP3A4 active agents: Patients must not be receiving any of the following potent CYP3A4 inducers or inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort. A list of other known CYP3A4 inducers and inhibitors that should be discontinued prior to initiation of protocol therapy and should be avoided during study therapy if reasonable alternatives exist is included in Appendix V.
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- Patients who are receiving systemic therapeutic treatment anticoagulation are not eligible. Patients receiving prophylactic systemic anticoagulation will be allowed with heparin or LMWH as long as eligibility PT/INR requirements are met. Concomitant anticoagulation with oral anticoagulations (e.g. warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg. Clopidogrel) are not allowed.
- Enzyme-inducing anticonvulsants: Patients must not have received enzyme-inducing anticonvulsants within 14 days prior to enrollment (See Appendix III for a list of unacceptable enzyme inducing anticonvulsants).
- QTc Agents: Patients who are receiving drugs that prolong QTc are not eligible (See Appendix IV for a list of agents).
- Patients must be able to swallow intact tablets. Patients who cannot swallow intact tablets are not eligible.
- Patients with active bleeding are not eligible. Specifically, no clinically significant GI bleeding, GI perforation, intra-abdominal abscess or fistula for 6 months prior to enrollment, no hemoptysis or other signs of pulmonary hemorrhage for 3 months prior to enrollment.
- Patients with evidence of an acute intracranial or intratumoral hemorrhage on CT or MRI are not eligible (patients with evidence of resolving hemorrhage will be eligible).
- Major surgery within 28 days of enrollment. Complete wound healing from major or minor surgery must have occurred prior to enrollment. Minor surgery (including uncomplicated tooth extractions) within 7 days of enrollment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible;
- Concurrent uncontrolled hypertension defined as sustained blood pressure>95% for age, height and gender (systolic or diastolic) despite optimal antihypertensive treatment within 7 days of the first dose of study treatment.
- Patients with any medical or surgical conditions that would interfere with gastrointestinal absorption of this oral agent are not eligible.
- Infection: Patients who have an uncontrolled infection are not eligible.
- Patients who have received a prior solid organ transplantation are not eligible.
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
- Subjects who have received cabozantinib or have an allergy to cabozantinib are excluded. Subjects who have previously received tyrosine kinase inhibitors are allowed.
- Subjects who have not received radiation therapy as part of their prior treatment are excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
Riley Hospital for Children at IU Health
Indianapolis, Indiana, 46202
About this study
This pilot will study the feasibility and exploratory efficacy of using Cabozantinib for recurrent or refractory central nervous system tumors for which there are no curative options. Patients will also be followed for safety, time to progression, event free survival and overall survival
- Being tested
- Cabozantinib
- Keywords
- High Grade Glioma, Cabozantinib, GBM, Children, AA
- Medical subject headings
- Glioblastoma, Astrocytoma, Brain Neoplasms, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabozantinibDrug
Also called XL 184, Cabometyx
Subjects will receive Cabozantinib
| Study group | Role | What they receive |
|---|---|---|
| Cabozantinib | Experimental | Cabozantininb will be taken daily at a dose of 40 mg/m2. Drug cycles will last 28 days and be continuous for up to 12 months of therapy on study. Receives: Drug: Cabozantinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Disease Response
To assess the number of participants with best response of CR, PR, SD or PD. Response criteria are assessed based on the product of the longest diameter and its longest perpendicular diameter.
Complete response (CR): Disappearance of all target lesions Partial response (PR): ≥50% decrease in the sum of the products of the two perpendicular diameters of all target lesions (up to 5), taking as reference the initial baseline measurements Stable disease (SD): Neither sufficient decrease in the sum of the products of the two perpendicular diameters of all target lesions to qualify for PR, nor sufficient increase in a single target lesion to qualify for PD.
Progressive Disease (PD): The appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Measured: 6 months
Secondary outcomes (2)
Overall Survival
To assess the number of participants who survived at 6 months.
Measured: 6 months
Number of Participants With Progression Free Survival
To assess the number of participants who had progression free survival at 6 months.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2016 (estimated)
- Study start18 May 2017
- Primary completion25 Aug 2020
- Study completion25 Aug 2020
Why it stopped: Failure to meet accrual goals.
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.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Scott Coven, Indiana University
- Investigators
- Scott Coven, DO, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02885324
- Sponsor's protocol ID
- IUSCC-0601
- Status last verified
- Oct 2022
- First submitted
- 24 Aug 2016
- Last updated
- 6 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Cabozantinib for Recurrent or Progressive Central Nervous System Tumors in Children
- ClinicalTrials.gov ID
- NCT02885324
- Acronym / sponsor ID
- IUSCC-0601
- Keywords
- High Grade Glioma, Cabozantinib, GBM, Children, AA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Failure to meet accrual goals.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- 18 May 2017 (actual)
- Primary completion
- 25 Aug 2020 (actual)
- Study completion
- 25 Aug 2020 (actual)
- First posted
- 31 Aug 2016 (estimated)
- Results
- Posted 15 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot will study the feasibility and exploratory efficacy of using Cabozantinib for recurrent or refractory central nervous system tumors for which there are no curative options. Patients will also be followed for safety, time to progression, event free survival and overall survival
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cabozantinib | Experimental | Drug: CabozantinibCabozantininb will be taken daily at a dose of 40 mg/m2. Drug cycles will last 28 days and be continuous for up to 12 months of therapy on study. |
Who may qualify
- Ages
- 2 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (22 listed)
- Age: Patients must be ≥2 years and ≤21 years of age
- Diagnosis: Patients with relapsed or refractory central nervous system tumors. Patients must have had histological verification of malignancy at original diagnosis or relapse. Metastatic disease to the spine or primary tumors in the spine are eligible. Patients may be in first, second, or third relapse. Subjects with intrinsic brain stem gliomas may be eligible with or without histological confirmation. Please contact study chair prior to enrollment.
- Disease Status: Patients must have measurable disease. Linear enhancement of leptomeningeal without measurable mass is excluded.
- Therapeutic Options: Patient's current disease state must be one for which there is no accepted standard therapy, no known curative therapy or therapy proven to prolong survival with an acceptable quality of life. For patients in whom surgery is feasible, maximal surgical resection must have occurred.
- Performance Level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix 1). Note: Neurologic deficits in patients must have been relatively stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
Key exclusion criteria (20 listed)
- Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogentic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two methods of birth control- a medically accepted barrier method of contraceptive method (e.g., male or female condom) and a second effective method of birth control- during protocol therapy and for at least 4 months after the last dose of cabozantinib. Abstinence is an acceptable method of birth control.
- Concomitant Medications:
- Patients must be able to swallow intact tablets. Patients who cannot swallow intact tablets are not eligible.
- Patients with active bleeding are not eligible. Specifically, no clinically significant GI bleeding, GI perforation, intra-abdominal abscess or fistula for 6 months prior to enrollment, no hemoptysis or other signs of pulmonary hemorrhage for 3 months prior to enrollment.
- Patients with evidence of an acute intracranial or intratumoral hemorrhage on CT or MRI are not eligible (patients with evidence of resolving hemorrhage will be eligible).
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 |
|---|---|---|
| CabozantinibAlso: XL 184, CabometyxSubjects will receive Cabozantinib | Drug | Cabozantinib |
Primary outcome
Number of Participants With Disease Response
Time frame: 6 months
To assess the number of participants with best response of CR, PR, SD or PD. Response criteria are assessed based on the product of the longest diameter and its longest perpendicular diameter. Complete response (CR): Disappearance of all target lesions Partial response (PR): ≥50% decrease in the sum of the products of the two perpendicular diameters of all target lesions (up to 5), taking as reference the initial baseline measurements Stable disease (SD): Neither sufficient decrease in the sum of the products of the two perpendicular diameters of all target lesions to qualify for PR, nor sufficient increase in a single target lesion to qualify for PD. Progressive Disease (PD): The appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
2 secondary outcomes
Overall Survival
Time frame: 6 months
Number of Participants With Progression Free Survival
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Scott Coven, DO principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cabozantinib in people with Glioblastoma Multiforme and Anaplastic Astrocytoma, run by Indiana University at 1 site 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 22 inclusion and 20 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: stopped early, as of the sponsor's last update on 6 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Disease Response (time frame: 6 months). 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 6 Oct 2022.