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Panitumumab and Irinotecan for Malignant Gliomas

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ClinicalTrials.gov Identifier: NCT01017653
Recruitment Status : Terminated (study did not reach benchmark efficacy rule at 16 subjects)
First Posted : November 20, 2009
Results First Posted : September 4, 2013
Last Update Posted : September 4, 2013
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Annick Desjardins, Duke University

Tracking Information
First Submitted Date  ICMJE November 19, 2009
First Posted Date  ICMJE November 20, 2009
Results First Submitted Date  ICMJE April 30, 2013
Results First Posted Date  ICMJE September 4, 2013
Last Update Posted Date September 4, 2013
Study Start Date  ICMJE February 2010
Actual Primary Completion Date October 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 29, 2013)
6-month Progression-free Survival (PFS) [ Time Frame: 6 months ]
Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause. Macdonald criteria are standard criteria in neuro-oncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of: 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), and 3) concomitant steroid use (as reported by the investigator).
Original Primary Outcome Measures  ICMJE
 (submitted: November 19, 2009)
6-month and median progression-free survival [ Time Frame: 6 months ]
Change History Complete list of historical versions of study NCT01017653 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 29, 2013)
  • One-Year Overall Survival [ Time Frame: 1 year ]
    Percentage of participants surviving 12 months from the start of study treatment. OS was defined as the time from the date of study treatment initiation to the date of the death due to any cause.
  • Safety of Panitumumab in Combination With Irinotecan [ Time Frame: 16 months ]
    Number of participants experiencing a toxicity ≥ grade 3 as graded per CTCAE v.3.0
  • Effect of Panitumumab in Combination With Irinotecan on Corticosteroid Dose [ Time Frame: Baseline and Day 29 ]
    Average change in corticosteroid dose from baseline to the end of cycle 1.
  • Relationship Between Epidermal Growth Factor Receptor (EGF-R) Mutational Analysis and Efficacy or Toxicity [ Time Frame: 16 months ]
    Number of participants with an abnormal fluorescence in situ hybridization (FISH) interpretation that 1) survived < 6 months and 2) experienced a ≥ grade 3 toxicity as graded per CTCAE v.3.0
  • Objective Response Rate [ Time Frame: 16 months ]
    Number of participants with an objective response (complete response or partial response) based on modified Macdonald criteria. A complete response is defined as the disappearance of all enhancing rumor and mass effect, off all corticosteroids, accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks. A partial response is defined as greater than or equal to 50% reduction in tumor size on MR (magnetic resonance) / CT(computed tomography) by bi-dimensional measurement on a stable or decreasing dose of corticosteroids, accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks.
  • Median Overall Survival (OS) [ Time Frame: 18 months ]
    Time in months from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2009)
  • 1 year and median overall survival and radiologic response [ Time Frame: 1 year ]
  • Incidence and severity of > or = to grade 3 toxicity, particularly rash and diarrhea [ Time Frame: 1 year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Panitumumab and Irinotecan for Malignant Gliomas
Official Title  ICMJE Phase II Study of Panitumumab in Combination With Irinotecan for Malignant Gliomas
Brief Summary

This is a phase II study of the combination of panitumumab with irinotecan in malignant glioma patients. The primary objective of the study is to determine the activity of the combination of panitumumab with irinotecan as measured by 6-month progression-free survival. Secondary objectives include the following- to determine the safety of panitumumab in combination with irinotecan in patients with malignant glioma; to determine the effect of panitumumab in combination with irinotecan on corticosteroid dose for each patient; to explore any relationship between epidermal growth factor receptor (EGF-R) mutational analysis and efficacy or toxicity; and, to determine the response rate and overall survival of recurrent glioblastoma (GBM) patients treated with panitumumab in combination with irinotecan.

The patients will have histologically documented grade 4 malignant gliomas (glioblastoma multiforme or gliosarcoma) that have failed at least one prior chemotherapy regimen and all patients will have received radiation therapy. This study will investigate second or greater line of therapy for recurrent grade 4 malignant glioma. The patient population will include 32 patients.

The patients will undergo a baseline magnetic resonance imaging (MRI) as well as a MRI after every six-week cycle to determine response and progression. After 16 patients with recurrent GBM are treated, an interim analysis will be conducted. The most common side effects associated with panitumumab have been dermatological (skin) problems such as erythema (redness of the skin), acneiform rash (skin eruptions of the face), skin exfoliation, pruritus (itching), skin fissures (skin tears), xerosis (dryness of the eye, skin, or mouth), and rash. The most common side effects associated with irinotecan have been decreased blood counts of platelets (increased risk of bleeding), white blood cells (increased risk of infection), red blood cells (anemia); diarrhea, constipation, nausea, vomiting, tiredness, fever, mouth sores, dehydration (excessive loss of body fluids), rash, itching, changes in skin color, swelling, numbness, tingling, dizziness, confusion, low blood pressure, sweating, hot flashes, hair loss, inflammation of the liver, flu-like symptoms, decreased urine output, shortness of breath, and pneumonia (inflammatory disease of the lungs).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malignant Glioma of Brain
Intervention  ICMJE
  • Drug: Irinotecan
    Irinotecan: for those patients on an enzyme-inducing anti-epileptic drug (EIAED), irinotecan will be dosed at 340 mg/m2 every other week. For those not on an EIAED, irinotecan will be dosed at 125 mg/m2. Treatment on both drugs will continue until tumor progression or unacceptable toxicity.
    Other Names:
    • Camptosar
    • CPT-11
  • Drug: Panitumumab
    Panitumumab, 6 mg/kg, as an intravenous infusion every other week. Treatment on both drugs will continue until tumor progression or unacceptable toxicity.
    Other Name: Vectibix
Study Arms  ICMJE Experimental: Panitumumab and irinotecan
Interventions:
  • Drug: Irinotecan
  • Drug: Panitumumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: December 4, 2012)
16
Original Estimated Enrollment  ICMJE
 (submitted: November 19, 2009)
32
Actual Study Completion Date  ICMJE October 2011
Actual Primary Completion Date October 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must have histologically confirmed diagnosis of primary malignant glioma (glioblastoma multiforme or gliosarcoma). Patients with recurrent disease whose diagnostic pathology confirmed grade IV malignant glioma (glioblastoma multiforme or gliosarcoma) will not need re-biopsy.
  • Age ≥ 18 years.
  • Evidence of measurable recurrent or residual primary central nervous system (CNS) neoplasm on contrast-enhanced MRI
  • An interval of at least 4 weeks between prior surgical resection, or major surgery requiring general anesthesia or 1 week between prior biopsy or minor surgical procedures and study enrollment. The subjects must have recovered from all surgery related toxicities.
  • An interval of at least 12 weeks between prior radiotherapy or 4 weeks from prior monthly chemotherapy, or 7 days from daily chemotherapy.
  • The lab values following the prior chemotherapy must return to the baseline prior to study enrollment.
  • Karnofsky ≥ 70%.
  • Hematocrit ≥ 29%, absolute neutrophil count (ANC) ≥ 1,500 cells/μl, platelets ≥ 125,000 cells/μl.
  • Serum creatinine ≤ 1.5 mg/dl, serum magnesium, potassium, calcium, chloride, and sodium ≥ the lower limit of normal, serum glutamic-oxaloacetic transaminase (SGOT) and bilirubin ≤ 1.5 times upper limit of normal.
  • Signed informed consent approved by the Institutional Review Board prior to patient entry.
  • If sexually active, patients will take contraceptive measures for the duration of the treatments, and for 6 months afterwards.

Exclusion Criteria:

  • Pregnancy or breast feeding
  • Co-medication that may interfere with study results; e.g. immuno¬suppressive agents other than corticosteroids.
  • Active infection requiring intravenous antibiotics.
  • uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) homozygous for the 7/7 genotype.
  • Pre-existing diarrhea greater than Grade 1.

Panitumumab-Specific Concerns:

[Subjects meeting any of the following criteria are ineligible for study entry]

  • Prior anti-epidermal growth factor receptor (EGFr) antibody therapy or treatment with small molecule EGFr inhibitors
  • Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrollment.
  • History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
  • History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with the study participation or investigational product(s) administration or may interfere with the interpretation of the results.
  • Subject unwilling or unable to comply with study requirements
  • Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
  • Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment.
  • Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection(testing is not required in the absence of clinical suspicion)
  • Patients with a history of deep venous thrombosis, pulmonary embolism or on therapeutic anti-coagulation.
  • Known allergy or hypersensitivity to any component of the study treatment(s)
  • Active infection requiring systemic intravenous treatment of any uncontrolled infections ≤14 days prior to enrollment/randomization.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01017653
Other Study ID Numbers  ICMJE Pro00015447
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Annick Desjardins, Duke University
Study Sponsor  ICMJE Annick Desjardins
Collaborators  ICMJE Amgen
Investigators  ICMJE
Principal Investigator: Annick Desjardins, MD, FRCPC Duke University
PRS Account Duke University
Verification Date July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP