PF-00299804 in Adult Patients With Relapsed/Recurrent Glioblastoma

NCT01112527 | Completed Phase 2 DMC

• 2 other identifiers: 09-468WS573383
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 4

Brief Summary

There are three arms to this study (A, B and C) The purpose of this research study during Arm A is to see how much of PF-00299804 gets into the brain tumor. For many brain tumors, one reason that chemotherapy drugs might not be effective is that the drug may not be able to get into the brain tumor and kill the cancer cells. We will determine how much PF-00299804 gets into the brain tumor by obtaining a sample of the tumor from the surgery that the participant already has scheduled. The purpose of this research study during Arm B and C, is to determine how well PF-00299804 works in killing cancer cells. PF-00299804 works by binding to specific proteins found on the surface of some cancer cells that promote a growth signal. Blocking this signal from reaching its target on the cancer cells may slow or stop the cancer from growing.

Conditions

Glioblastoma; GBM; Glioblastoma Multiforme

Keywords

PF-00299804

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  Assess progression-free survival at six months in patients with recurrent GBM and EGFR amplification in archival tumor material who are treated with continuous daily dosing of PF-00299804 (Arm B)

  2 years

Secondary Outcomes (3)

• Ability of PF-00299804 to cross the blood-brain barrier

  2 years

• Safety and tolerability

  2 years

• Anti-tumor response

  2 years

Study Arms (3)

Arm A

EXPERIMENTAL

Patients with Glioblastoma that has returned or grown after chemotherapy or radiation treatment and who will be having a standard operation to remove the tumor.

Drug: PF-00299804

Arm B

EXPERIMENTAL

Participants with glioblastoma at first recurrence who are not surgical candidates and who have not had prior anti-VEGF therapy.

Drug: PF-00299804

Arm C

EXPERIMENTAL

Participants with glioblastoma who are not surgical candidates and who are at first recurrence from a therapeutic regimen containing bevacizumab.

Drug: PF-00299804

Interventions

PF-00299804 DRUG

Taken orally once a day

Arm A; Arm B; Arm C

Eligibility Criteria

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

You may qualify if:

• years of age or older
• Histologically confirmed diagnosis of a recurrent primary WHO grade IV malignant glioma (glioblastoma). Patients with recurrent disease whose diagnostic pathology confirmed glioblastoma will not need re-biopsy. Patients with prior low-grade glioma or anaplastic glioma are eligible if histologic assessment demonstrates transformation to GBM.
• Evidence of EGFR gene amplification by fluorescence in situ hybridization (FISH) in archival tumor material.
• Patients must have at least 15 unstained slides or 1 tissue block (frozen or paraffin embedded) available from a prior biopsy or surgery.
• For Arm A: patients must be at first recurrence of GBM, must not have had previous anti-VEGF therapy, and must be candidates for surgical partial or gross-total resection.
• For Arm B: patients must be at first recurrence of GBM and must not have had prior anti-VEGF therapy.
• For Arm C: patients may have had an unlimited number of prior therapies for GBM, however must be at first recurrence from a therapeutic regimen containing bevacizumab
• Progressive disease on contrast-enhanced brain CT or MRI as defined by McDonald Criteria, or have documented recurrent glioblastoma on diagnostic biopsy.
• Prior to enrollment, there must be an interval of at least 2 weeks between prior surgical resection (1 week for intracranial biopsy) and adequate wound healing.
• Interval of at least 12 weeks from prior radiotherapy unless there is either: a) histopathologic confirmation of recurrent tumor, or b) new enhancement on MRI outside of XRT treatment field.
• Patients must have sufficient time to recover from prior therapy.
• Karnofsky Performance Score 70% or greater
• Adequate hematologic and liver function as outlined in the protocol
• Creatinine within normal institutional limits
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation and for at least 3 months thereafter.

You may not qualify if:

• Presence of extra-cranial metastatic disease
• Participants may not be receiving any other investigational agents
• Prior investigational therapy with an agent that is known or proposed to be active by action on any component of the EGFR tyrosine kinase, IGF1R, mTor, orc-MET pathways
• Patients who have been previously treated with an anti-VEGF agent will be excluded from Arm A and Arm B.
• Patients must not have received prior Gliadel wafers
• Any surgery (not including minor diagnostic procedures such as lymph node biopsy) within 2 weeks of baseline disease assessments; or not fully recovered from any side effects of previous procedures.
• Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drug.
• Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this protocol
• Patients with known interstitial lung disease
• Uncontrolled or significant cardiovascular disease
• Any patient with a history of significant cardiovascular disease, even if currently controlled, or who has signs or symptoms suggesting impaired left ventricular function in the judgment of the investigator must have a screening left ventricular ejection fraction evaluation by ECHO or MUGA. Patients with LVEF measurements below local institutional lower limit of normal or less then 50% will not be eligible.
• Individuals with a history of a different malignancy are ineligible except for the circumstances outlined in the protocol
• Patients who have had prior stereotactic radiotherapy, convection enhanced delivery or brachytherapy as gliosis/scarring from these modalities may limit delivery
• Patients will not be eligible if they present with leptomeningeal dissemination
• Pregnant women

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Dana-Farber Cancer Institute: collaborator
• Brigham and Women's Hospital: collaborator
• Henry Ford Hospital: collaborator
• Pfizer: collaborator

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

dacomitinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Tracy T. Batchelor, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 27, 2010
• First Posted: April 28, 2010
• Study Start: April 1, 2010
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: August 16, 2018

Record last verified: 2018-08

Locations

US (4)