Safety and Efficacy of PF-299804 (Dacomitinib), a Pan-HER Irreversible Inhibitor, in Patients With Recurrent Glioblastoma With EGFR Amplification or Presence of EGFRvIII Mutation. A Phase II CT.

NCT01520870 | Completed Phase 2 Results

• 1 other identifier: GEINO 11
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 12

Brief Summary

This multicenter, 2-stage, open-label, phase II trial aims to assess the efficacy and safety of dacomitinib in adult patients with recurrent Glioblastoma (GBM) with EGFR gene amplification and/or EGFRvIII mutation.

Conditions

Glioblastoma; Brain Tumor, Recurrent

Keywords

Dacomitinib; PF-299804; Glioblastoma, Recurrent; EGFR

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) at Six Months (PFS6m)

  Percentage of patients who have progressed / no progress after 6 months of treatment in each of the two cohorts.

  Baseline and after 6 months

Secondary Outcomes (6)

• Safety and Tolerability of Oral Administration of PF-00299804.

  Up to 42 months

• Anti-tumor Response

  Baseline and every 12 weeks

• Overall Survival (OS)

  Up to 42 months

• Response Duration

  Baseline and every 12 weeks

• Changes in the Use of Glucocorticoids

  Baseline and every 12 weeks

Study Arms (1)

PF-299804 (Dacomitinib)

EXPERIMENTAL

Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations.

Drug: PF-299804 (Dacomitinib)

Interventions

PF-299804 (Dacomitinib) DRUG

Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end.

PF-299804 (Dacomitinib)

Eligibility Criteria

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

You may qualify if:

• Ability to understand and sign the informed consent approved by the Ethic Committee.
• Men or women aged greater than or equal to 18.
• Patients with grade IV malignant glioma according to WHO classification (glioblastoma) in first relapse with histologically confirmed diagnosis by the central laboratory. Patients with previous low-grade glioma or anaplastic glioma (anaplastic astrocytoma or anaplastic oligodendroglioma), are not eligible, even if histological assessment demonstrates transformation to GBM.
• Patients in first relapse (or progression) to chemo-radiotherapy and temozolomide-based chemotherapy (Stupp4 scheme).
• All patients must have EGFR gene amplification by in situ hybridization fluorescent (FISH) and / or EGFRvIII mutation by PCR in tumor samples made by the central laboratory (Laboratory of Neuropathology. Hospital Universitario 12 de Octubre).
• For all study cohorts, patients must be at least 15 unstained slides or a block of paraffin-embedded tissue available from a previous biopsy or surgery (archived tumor samples previously).
• All patients must show progressive disease of the brain MRI is as defined in the Criteria RANO.
• Patients must have recovered from previous therapy: 28 days from the completionof any investigational drug and / or the termination of any cytotoxic therapy.
• ECOG performance status less than or equal to 2.
• Adequate bone marrow reserve, hematocrit greater than or equal to 29%, WBC\> 3000 / mcl,ANC greater than or equal to 1,500 cells / ul, platelets greater than or equal a100.000 cells / ul.
• Adequate hepatic function: bilirubin less than or equal to 1.5 times ULN, AST (SGOT) less than or equal to 2.5 x ULN.
• Creatinine within the center ULN or creatinine clearance \> 60 mL/min/1.73 m2 for subjects with creatinine levels above the center ULN.
• The patients in whom resection was made in the first tumor recurrence are eligible in the following cases:
• There is adequate recovery from surgery.
• There must be measurable or evaluable disease after surgery. For an adequate Radiological evaluation of residual disease, MRI must be completed within 72 hours after surgery or 4 weeks after surgery.

You may not qualify if:

• Presence of extra-cranial metastatic disease.
• Concomitant treatment with other investigational drugs.
• Prior treatment with an investigational drug/s known or are suspected to be active by the action of any component of the EGFR tyrosine kinase.
• Surgery of any kind (does not include diagnostic procedures such as minor lymph node biopsy) in the 2 weeks prior to baseline assessments of the disease, or presence of side effects of previous procedures.
• Presence of any clinically significant gastrointestinal abnormality that can affect oral administration, transit or absorption of study drug, such as the inability to take medication by mouth as tablets.
• Presence of any psychiatric or cognitive disorder that limits the understanding or the signature of informed consent and / or jeopardize the fulfillment of the requirements of this protocol.
• Significant or uncontrolled cardiovascular disease, including:
• Myocardial infarction within the previous 12 months
• Uncontrolled angina within the previos 6 months
• Congestive heart failure in the previous 6 months
• Known or suspected congenital long QT syndrome
• History of clinically significant ventricular arrhythmias of any type (as ventricular tachycardia, ventricular fibrillation or torsades de pointes)
• QTc prolongation on electrocardiogram prior to entry (\> 470 msec)
• History of second or third grade heart block (these patients may be eligible if you currently have a pacemaker)
• Heart rate \< 50/minute in the baseline electrocardiogram

Sponsors & Collaborators

• Grupo Español de Investigación en Neurooncología: lead
• Pfizer: collaborator

Study Sites (12)

Hospital Universitari Germans Trias I Pujol de Badalona

Badalona, Barcelona, 08916, Spain

Location

Institut Català D'Oncologia L'Hospitalet (Ico)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitario A Coruña

A Coruña, Coruña (A), 15006, Spain

Location

Hospital Del Mar

Barcelona, 08003, Spain

Location

Hospital de La Santa Creu I Sant Pau

Barcelona, 08025, Spain

Location

Complejo Hospitalario Regional Virgen de Las Nieves

Granada, 18004, Spain

Location

Complejo Hospitalario Universitario Insular-Materno Infantil

Las Palmas de Gran Canaria, 35016, Spain

Location

Hospital Ramón Y Cajal

Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, Spain

Location

Hospital Universitario Y Politécnico La Fe

Valencia, 46009, Spain

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms; Recurrence

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; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Important limitations of our study are the small sample size and the nonrandomized design, which preclude drawing firm conclusions, EGFR amplification, which has been used as a primary laboratory assessment, was tested in the primary tumor, and we have no evidence of the stability of this alteration in the recurrent GBs.

Results Point of Contact

• Title: Pau Doñate
• Organization: MFAR Clinical Research

investigacion@mfar.net

Study Officials

• Juan Sepúlveda, MD

  Hospital 12 de Octubre

  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: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2012
• First Posted: January 30, 2012
• Study Start: February 1, 2012
• Primary Completion: April 1, 2015
• Study Completion: March 9, 2017
• Last Updated: July 6, 2021
• Results First Posted: July 6, 2021

Record last verified: 2021-07

Locations

ES (12)