Carboplatin and Bevacizumab for Recurrent Ependymoma

NCT01295944 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 16000916-C-0009
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical research study is to learn if the combination of bevacizumab and carboplatin can help to control recurrent ependymoma. The safety of this drug combination will also be studied.

Conditions

Ependymoma; Anaplastic Ependymoma

Keywords

Chemotherapy; Brain Tumor; Spinal Cord Tumor; Malignancy; Neurologic

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants That Have Progressive Free Survival (PFS) After 1 Year

  Percentage of participants that have progressive disease after 1 year. Kaplan-Meier method is used for the analyses of PFS. Progression is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline. Clear worsening of any evaluable disease, or appearance of any new lesion/site, clear clinical worsening or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

  1 year

Secondary Outcomes (6)

• Number of Participants With a (Complete Response (CR) + Partial Response (PR))

  Up to 6 months and 1 week

• Overall Survival (OS)

  The time from treatment start date until date of death or date last known alive, up to 68 months

• Mean Core Symptom Severity With Daily Activities Using the MD Anderson Symptom Inventory for Brain Tumors (MDASI-BT)

  Completed at baseline, before a brain or spine magnetic resonance imaging (MRI)/clinical evaluation, and at cycle 2, cycle 4, and cycle 6 (each cycle is 28 days)

• Mean Core Symptom Severity With Daily Activities Using the MD Anderson Symptom Inventory for Spine Tumors (MDASI-SP) Instrument

  Completed at baseline, before a brain or spine magnetic resonance imaging (MRI)/clinical evaluation, and at cycle 2, cycle 4, and cycle 6 (each cycle is 28 days)

• Mean Symptom Interference With Daily Activities Using the MD Anderson Symptom Inventory for Brain Tumors (MDASI-BT)

  Completed at baseline, before a brain or spine magnetic resonance imaging (MRI)/clinical evaluation, and at cycle 2, cycle 4, and cycle 6 (each cycle is 28 days)

Other Outcomes (1)

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approximately, 112 months and 28 days.

Study Arms (1)

1/Carboplatin and Bevacizumab for Recurrent Ependymoma

EXPERIMENTAL

The total duration of treatment will be 6 cycles. After cycle 6, carboplatin should be discontinued, but bevacizumab may be continued at the discretion of the treating physician.

Drug: Carboplatin; Drug: Bevacizumab

Interventions

Carboplatin DRUG

Carboplatin will be given on day 1 of each cycle; the carboplatin dose should be calculated using the Calvert formula: Carboplatin dose (mg) = target Area Under the Curve (AUC) x (Creatinine clearance (CrCl) + 25; The total duration of treatment will be 6 cycles. After cycle 6, carboplatin should be discontinued.

Also known as: Paraplatin

1/Carboplatin and Bevacizumab for Recurrent Ependymoma

Bevacizumab DRUG

Bevacizumab will be administered on days 1 and 15 of each cycle. Bevacizumab will be administered at a dose of 10 mg/kg; The total duration of treatment will be 6 cycles. After cycle 6, bevacizumab may be continued at the discretion of the treating physician.

Also known as: Avastin

1/Carboplatin and Bevacizumab for Recurrent Ependymoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven intra-cranial or spinal ependymoma or anaplastic ependymoma. There must be pathologic or imaging confirmation of tumor progression or regrowth.
• The patient must have at least 1 block of tissue or 15 unstained slides at a minimum available for central pathology review and molecular profiling of the tissue sample.
• All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have signed an authorization for the release of their protected health information.
• Patients must be greater than or equal to 18 years old.
• Patients must have a Karnofsky performance status of \> 60.
• Patients must have adequate bone marrow function (white blood cell (WBC) greater than or equal to 3,000/microliter, absolute neutrophil count (ANC) greater than or equal to 1,500/mm\^3, platelet count of greater than to equal to 100,000/mm\^3, and hemoglobin greater than or equal to 10 gm/dl), adequate liver function (Serum glutamic oxaloacetic transaminase (SGOT) \[aspartate aminotransferase (AST) \<92.5 Units/L\] and bilirubin less than or equal to 1.5 mg/dL), and adequate renal function (creatinine \< 1.5 mg/dL and calculated creatinine clearance greater than or equal to 60 cc/min) before starting therapy. Eligibility level for hemoglobin may be reached by transfusion.
• Patients must have shown unequivocal radiographic evidence for tumor progression by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
• At the time of registration: Patients must have recovered from the toxic effects of prior therapy: greater than or equal to 28 days from any investigational agent, greater than or equal to 28 days from prior cytotoxic therapy, greater than or equal to 14 days from vincristine, greater than or equal to 42 days from nitrosoureas, greater than or equal to 21 days from procarbazine administration, and greater than or equal to 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of non-cytotoxic agents should be directed to the Principal Investigator.
• Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
• They have recovered from the effects of surgery.
• A minimum of 28 days have elapsed from the day of surgery to the day of registration Step 2.
• For core or needle biopsy, a minimum of 7 days must have elapsed prior to registration Step 2.
• Residual disease following resection of recurrent ependymoma is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a CT/ MRI should be done no later than 96 hours in the immediate post-operative period or at least 4 weeks post-operatively, within 14 days prior to consent. If the within 96-hour after surgery scan is more than 14 days before consent the scan needs to be repeated. If the steroid dose is increased between the date of imaging and consent, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.
• Patients must have failed prior radiation therapy\* and must have an interval of greater than or equal to 42 days from the completion of radiation therapy to study entry. Note: Patients with an indication for craniospinal radiotherapy (i.e., extensive leptomeningeal disease) but have refused palliative craniospinal radiotherapy are eligible.
• Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either positron emission tomography (PET) or Thallium scanning, MR spectroscopy, or surgical/pathological documentation of disease.

You may not qualify if:

• Patients with any significant medical illnesses that in the investigators opinion cannot be adequately controlled with appropriate therapy or would compromise the patients ability to tolerate this therapy.
• Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma insitu of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
• Patients with an active infection or serious intercurrent medical illness.
• Patients found to be pregnant/breast feeding. Patients must not be pregnant because animal studies show that carboplatin and bevacizumab are teratogenic
• Patients with any disease that will obscure toxicity or dangerously alter drug metabolism.
• Patients who have received prior therapy with bevacizumab, or related drugs (previous therapy with carboplatin is allowed).
• Inadequately controlled hypertension (defined as systolic blood pressure \>150 millimeters of mercury (mmHg) and/or diastolic blood pressure \> 100 mmHg) despite antihypertensive medication.
• New York Heart Association (NYHA) Grade II or greater congestive heart failure.
• History of myocardial infarction or unstable angina within 12 months prior to Day 1.
• History of stroke or transient ischemic attack.
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1.
• History of hemoptysis (greater than or equal to 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1.
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation). (To be eligible, Prothrombin time/international normalized ratio (prothrombin time (PT) international normalized ratio (INR)) should be \< 1.4 for patients not on warfarin.)
• Patients receiving full-dose anticoagulants therapy (e.g., warfarin or Low-molecular-weigh (LMW) heparin) and does not meet both of the following criteria:
• No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices).

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Massachusetts General Hospital/Dana Farber

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Ependymoma; Brain Neoplasms; Spinal Cord Neoplasms; Neoplasms; Neurologic Manifestations

Interventions

Carboplatin; Bevacizumab

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Kevin Camphausen
• Organization: National Cancer Institute

camphauk@mail.nih.gov

240-760-6205

Study Officials

• Kevin Camphausen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 11, 2011
• First Posted: February 15, 2011
• Study Start: April 27, 2011
• Primary Completion: September 23, 2020
• Study Completion: May 14, 2021
• Last Updated: August 5, 2025
• Results First Posted: December 28, 2021

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be shared before publication and at the time of publication or shortly thereafter.
• Access Criteria: Data will be shared through an National Institutes of Health funded or approved public repository (clinicaltrials.gov); Biomedical Translational Research Information System (BTRIS), and approved outside collaborators under appropriate individual agreements.

Locations

US (2)