Ph I Dasatinib + Erlotinib in Recurrent MG

NCT00609999 | Completed Phase 1 DMC

• 1 other identifier: Pro00002272
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

Primary: To determine maximum tolerated dose \& dose limiting toxicity of dasatinib when combined w erlotinib among pts w recurrent MG Secondary: To further evaluate safety \& tolerability of dasatinib + erlotinib To evaluate pharmacokinetics of dasatinib when administered w erlotinib among recurrent MG pts who are on \& not on CYP-3A enzyme inducing anti-epileptic drugs To evaluate for anti-tumor activity with this regimen in this patient population

Conditions

Glioblastoma; Gliosarcoma

Keywords

Glioblastoma; Gliosarcoma; GBM; Recurrent MG; Erlotinib; Dasatinib; Brain tumor; Malignant glioma; Tarceva; Sprycel

Outcome Measures

Primary Outcomes (1)

• To determine MTD & DLT of Dasatinib when combined w Erlotinib among pts w Recurrent MG

  12 months

Secondary Outcomes (3)

• To further evaluate safety & tolerability of Dasatinib + Erlotinib

  12 months

• To evaluate the PK of Dasatinib when administered w Erlotinib among Recurrent MG pts who are on & not on EIAEDs

  12 months

• To evaluate for anti-tumor activity w this regimen in this pt population

  12 months

Study Arms (2)

Stratum A

EXPERIMENTAL

Pts not on EIAEDs

Drug: Erlotinib and Dasatinib

Stratum B

EXPERIMENTAL

Pts on EIAEDs

Drug: Erlotinib and Dasatinib

Interventions

Erlotinib and Dasatinib DRUG

You will begin study drug regimen on day 1 of cycle 1 w Dasatinib. If you are undergoing Dasatinib pharmacokinetic blood analysis, Dasatinib will be taken alone until initial PK assessments are collected. Erlotinib will be begin after initial Dasatinib PK assessments are collected \& will continue to be administered w Dasatinib on continuous daily dosing schedule. Initial Dasatinib PK assessments will be collected over 24hrs between days 3-7 of cycle 1 \& at end of cycle 1. If you are not undergoing Dasatinib PK collections you will begin both Dasatinib \& Erlotinib together on day 1 of cycle 1. Both drugs will be given in continuous daily oral manner. Cycle is defined as Dasatinib \& Erlotinib given daily for 28 days for purpose of scheduling evaluations.

Also known as: Dasatinib, Erlotinib, Tarceva, Sprycel

Stratum A; Stratum B

Eligibility Criteria

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

You may qualify if:

• Diagnosis of recurrent/progressive WHO grade IV MG or WHO grade III MG. Pts with prior low-grade glioma are eligible if histologic assessment demonstrates transformation to WHO grade III / IV MG
• \>18 yrs
• Karnofsky Performance Status \>70 percent
• Pts presenting in 1st, 2nd / 3rd relapse. Prior therapy must have included external beam XRT
• Adequate bone marrow, liver \& renal function as assessed by following:
• Hemoglobin\>9.0g/dl
• ANC\>1,500/mm3
• Platelet count\>100,000/mm3
• Total bilirubin\<1.5 x ULN
• ALT \& AST\<2.5 x ULN
• INR\<1.5 or PT/PTT within normal limits. Pts receiving anti-coagulation treatment w low-molecular weight heparin allowed to participate, oral warfarin is not permitted
• Creatinine\<1.5 x ULN
• Serum Na, K+, Mg2+, Phosphate \& Ca2+ \>LLN
• Interval\<2 wks between prior surgical resection \& initiation of study regimen
• Interval \<12 weeks from completion of standard, daily XRT, unless one of following occurs: new area of enhancement on MRI imaging that is outside XRT field; biopsy proven recurrent tumor; / radiographic evidence of progressive tumor on 2 consecutive scans \>4 wks apart.

You may not qualify if:

• No prior dasatinib / oral EGFR-inhibitor therapy
• Pregnancy/breast feeding
• History of significant concurrent illness
• \>3 prior episodes of progressive disease
• Significant cardiac disease
• Excessive risk of bleeding as defined by stroke \<6 months, history of CNS / intraocular bleed,/ septic endocarditis.
• Concurrent severe and/or uncontrolled medical disease that could compromise participation in study including any of following: pleural / pericardial effusion of any grade; uncontrolled diabetes; uncontrolled hypertension; active clinically serious infection \>CTCAEv3 Gr2 requiring active intervention; history of clinically-significant bleeding diathesis or coagulopathy including platelet function disorder or acquired bleeding disorder within 1yr; impairment of GI function /GI disease that may significantly alter absorption of study regimen; ongoing or recent significant gastrointestinal bleeding
• Thrombolic or embolic events such as cerebrovascular accident including transient ischemic attacks \<6 months
• Any hemorrhage/bleeding event \>CTCAEv3AE Gr3 within 4wks of 1st dose of study drug
• Serious non-healing wound, ulcer, /bone fracture
• Major surgery, open biopsy /significant traumatic injury \<4 weeks of 1st study drug
• Known HIV infection/chronic Hepatitis B/C
• Pt is \<3yrs free of another primary malignancy except: if other primary malignancy is either not currently clinically significant/does not require active intervention. Existence of any other malignant disease is not allowed.
• Pts unwilling to/unable to comply with protocol including ability to swallow whole pills/presence of any malabsorption syndrome
• Concurrent administration of warfarin, rifampin/St. John's Wort

Sponsors & Collaborators

• Duke University: lead
• Bristol-Myers Squibb: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at DUKE

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms; Glioma

Interventions

Erlotinib Hydrochloride; Dasatinib

Condition Hierarchy (Ancestors)

Astrocytoma; 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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Pyrimidines

Study Officials

• Annick Desjardins, MD, FRCPC

  Duke Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2008
• First Posted: February 7, 2008
• Study Start: January 1, 2008
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: July 16, 2014

Record last verified: 2012-04

Locations

US (1)