Ph I Dasatinib + Erlotinib in Recurrent MG

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Genentech
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00609999
First received: January 25, 2008
Last updated: July 15, 2014
Last verified: April 2012
  Purpose

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


Condition Intervention Phase
Glioblastoma
Gliosarcoma
Drug: Erlotinib and Dasatinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Dasatinib Plus Erlotinib in Recurrent Malignant Glioma

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • To determine MTD & DLT of Dasatinib when combined w Erlotinib among pts w Recurrent MG [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To further evaluate safety & tolerability of Dasatinib + Erlotinib [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • To evaluate the PK of Dasatinib when administered w Erlotinib among Recurrent MG pts who are on & not on EIAEDs [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • To evaluate for anti-tumor activity w this regimen in this pt population [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 47
Study Start Date: January 2008
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stratum A
Pts not on EIAEDs
Drug: Erlotinib and Dasatinib
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.
Other Names:
  • Dasatinib
  • Erlotinib
  • Tarceva
  • Sprycel
Experimental: Stratum B
Pts on EIAEDs
Drug: Erlotinib and Dasatinib
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.
Other Names:
  • Dasatinib
  • Erlotinib
  • Tarceva
  • Sprycel

Detailed Description:

Tarceva administered on continuous oral dosing schedule at 150 mg/day for pts not on EIAEDs & 450 mg/day for pts on EIAEDs. Starting dose level of dasatinib will be 100 mg once day via continuous oral daily dosing. Dasatinib will be increased in successive cohorts of enrolled pts. Pts will remain on treatment until excessive toxicity, progressive disease, withdrawal of consent/death.

Pts have confirmed diagnosis of recurrent/progressive WHO gr IV MG / WHO grade III MG. Phase I 3+3 dose escalation design w 2 independently escalated stratum: stratum A-pts not on CYP3A-enzyme inducing anti-epileptic drugs; stratum B-pts on EIAEDs. Assessment of safety will be based mainly on frequency of adverse events, particularly adverse events leading to discontinuation of treatment & on number of significant lab abnormalities.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • Interval <4weeks from prior chemotherapy unless there is unequivocal evidence of tumor progression & pt has recovered from all anticipated toxicities from prior therapy
  • Interval <4weeks from prior investigational agent unless there is unequivocal evidence of tumor progression & pt has recovered from all anticipated toxicities from prior therapy
  • Signed written informed consent including HIPAA according to institutional guidelines. Signed informed consent must be obtained prior to any study specific procedures
  • If sexually active, pts will take contraceptive measures for duration of treatments & for 4 weeks following discontinuation of dasatinib & Erlotinib.
  • Women of childbearing potential must have negative serum or urine pregnancy test within 72 hrs prior to start of study drug administration

Exclusion Criteria:

  • 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
  • Subjects w hypokalemia/hypomagnesemia if it cannot be corrected
  • Prisoners/subjects who are compulsorily detained for treatment of either psychiatric/physical illness
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00609999

Locations
United States, North Carolina
Duke University Health System
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Bristol-Myers Squibb
Genentech
Investigators
Principal Investigator: Annick Desjardins, MD, FRCPC Duke University Health System
  More Information

Additional Information:
No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00609999     History of Changes
Other Study ID Numbers: Pro00002272
Study First Received: January 25, 2008
Last Updated: July 15, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Duke University:
Glioblastoma
Gliosarcoma
GBM
Recurrent MG
Erlotinib
Dasatinib
Brain tumor
Malignant glioma
Tarceva
Sprycel

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Erlotinib
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014