Ph. II Treatment of Adults w Primary Malignant Glioma w Irinotecan + Temozolomide

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00616005
First received: February 3, 2008
Last updated: June 17, 2013
Last verified: August 2010
  Purpose

Objective:

To determine activity of combo of Irinotecan + Temozolomide To further characterize any toxicity associated w combo of Irinotecan + Temozolomide


Condition Intervention Phase
Glioblastoma
Drug: Temodar and Irinotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Treatment of Adults With Primary Malignant Glioma With Irinotecan Plus Temozolomide

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity assessment [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 41
Study Start Date: November 2005
Study Completion Date: June 2009
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1
Pts taking EIAEDs
Drug: Temodar and Irinotecan
Temozolomide-orally 200mg/m2 in fasting state 1hr prior to CPT-11 infusion. Temozolomide-day 1 of treatment cycle & every 24hrs thereafter for 5days w treatment cycles repeated every 6wks. Treatment cycles repeated up to maxi of 3 cycles until occurrence of either unacceptable toxicity/evidence of disease progression. CPT-11-intravenously in fasting state over 90min. CPT-11 1hr after Temozolomide administration on day 1 of treatment cycle. CPT-11-days 1, 8, 22, & 29 of 6wk treatment cycle. Treatment cycles may be repeated up to maxi of 3 cycles until occurrence of either unacceptable toxicity/evidence of disease progression. Dose of CPT-11 will be based on whether pt is receiving EIAEDs due to increased drug clearance produced by agents. For pts receiving EIAEDs, CPT-11 dose of 325mg/m2 administered. For pts not receiving EIAEDs, CPT-11 dose of 125mg/m2 administered.
Other Names:
  • Temodar - Temozolomide
  • Irinotecan - Camptosar - CPT11
2
Pts not taking EIAEDs
Drug: Temodar and Irinotecan
Temozolomide-orally 200mg/m2 in fasting state 1hr prior to CPT-11 infusion. Temozolomide-day 1 of treatment cycle & every 24hrs thereafter for 5days w treatment cycles repeated every 6wks. Treatment cycles repeated up to maxi of 3 cycles until occurrence of either unacceptable toxicity/evidence of disease progression. CPT-11-intravenously in fasting state over 90min. CPT-11 1hr after Temozolomide administration on day 1 of treatment cycle. CPT-11-days 1, 8, 22, & 29 of 6wk treatment cycle. Treatment cycles may be repeated up to maxi of 3 cycles until occurrence of either unacceptable toxicity/evidence of disease progression. Dose of CPT-11 will be based on whether pt is receiving EIAEDs due to increased drug clearance produced by agents. For pts receiving EIAEDs, CPT-11 dose of 325mg/m2 administered. For pts not receiving EIAEDs, CPT-11 dose of 125mg/m2 administered.
Other Names:
  • Temodar - Temozolomide
  • Irinotecan - Camptosar - CPT11

Detailed Description:

Objectives of study are to determine activity of combo of Irinotecan + Temozolomide & to further characterize any toxicity associated w combo of Irinotecan + Temozolomide. Temozolomide administered orally at 200mg/m2 in fasting state 1hr prior to CPT-11 infusion. Temozolomide administered on day 1 of treatment cycle & every 24hrs thereafter for 5 days w treatment cycles repeated every 6wks. Treatment cycles may be repeated up to maxi of 3 cycles until occurrence of either unacceptable toxicity/evidence of disease progression. At end of 3rd cycle/if cycles are stopped early for toxicity or progression, subject will undergo radiation therapy. CPT-11 administered intravenously in fasting state over 90min. CPT-11 will begin 1hr after Temozolomide administration on day 1 of treatment cycle. CPT-11 administered on days 1, 8, 22, & 29 of 6wk treatment cycle. Treatment cycles may be repeated up to maxi of 3 cycles until occurrence of either unacceptable toxicity/evidence of disease progression. Dose of CPT-11 will be based on whether pt is receiving CYP3A4-inducing antiepileptic drugs due to increased drug clearance produced by these agents. For pts receiving EIAEDs including phenytoin, fosphenytoin, oxcarbazepine, phenobarbital/ primidone, CPT-11 dose of 325mg/m2 administered. For pts not receiving EIAEDs, CPT-11 dose of125 mg/m2 administered.

Subjects have newly diagnosed histologically proven supratentorial glioblastoma multiforme. Toxicities associated w CPT-11 are anemia, decreased blood counts, diarrhea, constipation, nausea, vomiting, tiredness, fever, mouth sores, dehydration, rash, itching, changes in skin color, swelling, numbness, tingling, dizziness, confusion, low blood pressure, sweating, hot flashes, hair loss, inflammation of liver, flu-like symptoms, decreased urine output, shortness of breath,& pneumonia. Low white blood cell & platelet counts may be associated w risk of infection/bleeding, respectively. Irinotecan has also caused birth defects in animals. Most frequent toxicities in earlier studies have been low white blood cells & diarrhea, & death has been seen from these & other side effects. Temozolomide has been well tolerated by both adults & children w most common toxicity being mild myelosuppression. Other, less likely, potential toxicities include nausea & vomiting, constipation, headache, alopecia, rash, burning sensation of skin, esophagitis, pain, diarrhea, lethargy, hepatotoxicity, anorexia, fatigue & hyperglycemia. Hypersensitivity reactions have not yet been noted w Temozolomide. As in case w many anti-cancer drugs, Temozolomide may be carcinogenic.

  Eligibility

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

Inclusion Criteria:

  • Pts have histologically proven supratentorial GBM
  • Pts have newly diagnosed disease
  • There must be measurable disease on contrast-enhanced magnetic resonance imaging performed <14 days before drug administration. Those who underwent resection must have MRI <72 hrs/ >14 days after surgery
  • Prior Surgical Resection/Biopsy: Although surgical resection is not required, pts must be treated <42 days of surgery or biopsy
  • Age >18 yrs
  • Karnofsky Performance Status >70 percent
  • Serum creatinine < 1.5 x ULN
  • Absolute neutrophil count >1500 cells/microliter; platelet count >100,000 cells/microliter
  • Serum SGOT & total bilirubin <2.5 x ULN
  • Signed informed consent, approved by IRB, will be obtained prior to initiating treatment
  • Pts must agree to practice effective birth control measures while on study & for 2 months after completing therapy

Exclusion Criteria:

  • Pregnant/breast feeding women / women/men w reproductive potential not practicing adequate contraception. This therapy may be associated w potential toxicity to fetus/child that exceeds minimum risks necessary to meet health needs of mother
  • Active infection requiring intravenous antibiotics
  • Known diagnosis of HIV infection
  • Pts w history of another primary malignancy that currently requires active intervention
  • Pts unwilling/unable to comply w protocol due to serious medical/psychiatric condition
  • Pts who underwent surgical resection for GBM <2 weeks of start of treatment
  • Pts who have received prior chemo, biologic therapy, XRT, interstitial brachytherapy/radiosurgery to brain
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00616005

Locations
United States, North Carolina
Duke University Health System
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Pfizer
Investigators
Principal Investigator: David A. Reardon, MD Duke University Health System
  More Information

Additional Information:
No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00616005     History of Changes
Other Study ID Numbers: Pro00012939, 8044
Study First Received: February 3, 2008
Last Updated: June 17, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Glioblastoma
GBM
Brain tumor
Temodar
Temozolomide
Irinotecan
CPT-11
Camptosar
Malignant glioma
Anaplastic astrocytoma
Glioblastoma multiforme

Additional relevant MeSH terms:
Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Irinotecan
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 21, 2014