Bevacizumab and Erlotinib After Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma

NCT00720356 | Completed Phase 2 Results DMC

• 3 other identifiers: NU 07C3BTTC08-01STU00002792
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 9

Brief Summary

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bevacizumab together with erlotinib may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with erlotinib works after radiation therapy and temozolomide in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult glioblastoma; adult gliosarcoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival (OS) will be measured from the start of treatment until death from any cause. At data cut off patients remaining alive will be censored at the last known date of contact.

  From start of treatment, during treatment and every 3 months following the end of treatment until death. Median follow up at time of OS data was 33 months.

Secondary Outcomes (4)

• Progression-free Survival at 12 Months

  At 12 months from start of treatment

• Response Rate (RR)

  From the start of treatment, every 2 cycles (1 cycle = 28 days) during treatment until progressive disease

• Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population

  From the start of treatment, at the beginning of every cycle (1 cycle = 28 days) during treatment until 30 days after completion of treatment for up to 49 cycles.

• Progression Free Survival at 18 Months

  At 18 months from start of treatment

Other Outcomes (2)

• Changes in Tumor Blood Flow Based on MR Perfusion

  Prior to study treatment (after surgery, but before radiation), just before study treatment (within 14 days prior to first treatment) and then every 2 cycles during study treatment, where 1 cycle equals 28 days for a maximum of 49 cycles.

• Gene Methylation Studies (Optional)

  At baseline and then plasma only will be collected every odd cycle (1 cycle = 28 days) during treatment for a maximum of 49 cycles.

Study Arms (1)

Treatment

EXPERIMENTAL

erlotinib and bevacizumab

Drug: bevacizumab; Drug: erlotinib hydrochloride

Interventions

bevacizumab DRUG

10mg/kg administered intravenously every 2 weeks

Also known as: Avastin

Treatment

erlotinib hydrochloride DRUG

150 mg/daily orally

Also known as: erlotinib, CP-358, 774, Tarceva

Treatment

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed newly diagnosed glioblastoma multiforme (GBM) or gliosarcoma * Undergoing or plan to undergo treatment with radiotherapy and concurrent temozolomide for 6 weeks * Unmethylated MGMT promoter status must be determined before completing radiotherapy * Tumor must be MGMT negative to receive bevacizumab and erlotinib hydrochloride * Patients who are post biopsy or tumor resection allowed provided a post-operative MRI is done no more than 96 hours after surgery (in order for an accurate assessment to be done post radiotherapy): * Evaluable or measurable disease after resection of recurrent tumor is not mandated for eligibility * Patients who started radiotherapy and temozolomide prior to study entry are eligible as long as the gene methylation status is determined before starting bevacizumab and erlotinib hydrochloride * Radiotherapy plans need to be verified to confirm the treatment plan meets the study requirement based on the PI assessment * No progressive disease based on MRI or CT scan per the investigators assessment PATIENT CHARACTERISTICS: * Karnofsky performance status 70-100% * Life expectancy \> 12 weeks * WBC \> 3,000/μL * ANC \> 1,500/mm³ * Platelet count \> 100,000/mm³ * Hemoglobin \> 10 g/dL * SGOT/SGPT \< 3 times upper limit of normal (ULN) * Bilirubin \< 3 times ULN * Creatinine \< 1.5 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after completion of study treatment * No significant medical illness that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy, would compromise the patient's ability to tolerate this therapy, or any disease that will obscure toxicity or dangerously alter drug metabolism * No proteinuria at screening, as demonstrated by either of the following: * Urine protein:creatinine (UPC) ratio \< 1.0 * Urine dipstick for proteinuria \< 2+ OR ≤ 1g protein by 24-hour urine collection * No inadequately controlled hypertension (defined as systolic blood pressure \> 150 mm Hg and/or diastolic blood pressure \> 100 mm Hg) on antihypertensive medications * No history of hypertensive crisis or hypertensive encephalopathy * No New York Heart Association class II-IV congestive heart failure * No history of myocardial infarction or unstable angina within 6 months prior to study enrollment * No history of stroke or transient ischemic attack within 6 months of study enrollment * No symptomatic peripheral vascular disease * No significant vascular disease (i.e., aortic aneurysm or aortic dissection) * No evidence of bleeding diathesis or coagulopathy * No significant traumatic injury within 28 days prior to study enrollment * No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment * No serious, nonhealing wound, ulcer, or bone fracture * No known HIV positivity * HIV testing is not required for study participation * No history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years PRIOR CONCURRENT THERAPY: * No chemotherapy is allowed prior to starting radiotherapy and temozolomide, including polifeprosan 20 with carmustine implant (Gliadel wafers) * No major surgical procedure or open biopsy within 28 days prior to study enrollment or the anticipation of need for major surgical procedure during the course of the study * No core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment * Concurrent nonenzyme-inducing anticonvulsants allowed * More than 2 weeks (before starting erlotinib hydrochloride and bevacizumab) since prior and no concurrent enzyme-inducing anticonvulsant * No other concurrent experimental agents * Not concurrently participating in other clinical trials

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Northwestern University: lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (9)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

M.D. Anderson Cancer Center at Orlando

Orlando, Florida, 32806-2134, United States

Location

Northwestern University, Northwestern Medical Faculty Foundation

Chicago, Illinois, 60611-3013, United States

Location

Evanston Hospital

Evanston, Illinois, 60201-1781, United States

Location

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Neuro-Oncology Associates at Baylor University Medical Center, Dallas

Dallas, Texas, 75246, United States

Location

M.D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

The Methodist Hospital Neurological Institute

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 19024, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma

Interventions

Bevacizumab; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Jeffery Raizer, MD
• Organization: Northwestern University

Jeffrey.Raizer@nm.org

312-503-4724

Study Officials

• Jeffrey J. Raizer, MD

  Robert H. Lurie Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: July 19, 2008
• First Posted: July 22, 2008
• Study Start: July 7, 2009
• Primary Completion: June 24, 2014
• Study Completion: July 5, 2018
• Last Updated: October 26, 2018
• Results First Posted: October 26, 2018

Record last verified: 2018-10

Locations

US (9)