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A Phase 1, Open-Label, Dose Escalation Study of ANG1005 in Patients With Malignant Glioma

This study has been completed.
Sponsor:
Information provided by:
Angiochem Inc
ClinicalTrials.gov Identifier:
NCT00539344
First received: October 2, 2007
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

This is a phase 1, multi-centre, sequential cohort, open-label, dose-escalation study of the safety, tolerability, and PK of ANG1005 in patients with recurrent or progressive malignant glioma. ANG1005 will be given by IV infusion once every 21 days (1 treatment cycle). Each patient will participate in only 1 dose group and will receive up to 6 cycles of treatment provided there is no evidence of tumor progression, there is recovery to ≤Grade 1 or baseline nonhematologic, ANG1005-related toxicity (except alopecia), the absolute neutrophil count is ≥1.5 x 109/L, and the platelet count is ≥100 x 109/L.


Condition Intervention Phase
Recurrent or Progressive Malignant Glioma
Drug: ANG1005
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Phase 1, Open-Label, Dose Escalation Study of ANG1005 in Patients With Malignant Glioma

Resource links provided by NLM:


Further study details as provided by Angiochem Inc:

Primary Outcome Measures:
  • To characterize the safety and tolerability of intravenously administered ANG1005 in patients with malignant glioma. [ Time Frame: On-going ] [ Designated as safety issue: Yes ]
  • To identify the maximum tolerated dose (MTD) of ANG1005 in patients with malignant glioma. [ Time Frame: End of dose escalation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To examine the pharmacokinetics (PK) of ANG1005. [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • To confirm the safety and tolerability of ANG1005 at the MTD. [ Time Frame: End of dose escalation ] [ Designated as safety issue: Yes ]
  • To assess the immunogenicity of ANG1005. [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • To obtain preliminary information about the antitumor activity of ANG1005 in patients with malignant glioma. [ Time Frame: On-going ] [ Designated as safety issue: No ]
  • To obtain preliminary information about whether or not ANG1005 crosses the blood- brain barrier into malignant glioma tumors (Sub-study). [ Time Frame: On-going ] [ Designated as safety issue: No ]

Enrollment: 63
Study Start Date: October 2007
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: ANG1005
IV infusion once every 21 days

Detailed Description:

This is a phase 1, multi-centre, sequential cohort, open-label, dose-escalation study of the safety, tolerability, and PK of ANG1005 in patients with recurrent or progressive malignant glioma. ANG1005 will be given by IV infusion once every 21 days (1 treatment cycle). Each patient will participate in only 1 dose group and will receive up to 6 cycles. Patients may receive additional cycles of ANG1005 if there is no evidence of tumor progression, there is recovery to ≤Grade 1 or baseline nonhematologic, ANG1005-related toxicity (except alopecia), the absolute neutrophil count is ≥1.5 x 109/L, and the platelet count is ≥100 x 109/L.

Initially, cohorts of 1 - 3 patients will be enrolled into each dose group. Dose escalation by dose doubling will be done for the first 3 dose groups followed by a modified Fibonacci dose escalation scheme with increases of 67%, 50%, 40% and 33% thereafter. If > 1 patient in a cohort experience an emergent ≥ Grade 2 drug-related toxicity during the first treatment cycle, then a minimum of 3 patients will be enrolled into that, and all subsequent cohort(s) and dose doubling will be stopped if applicable.

If > 1 patient in a cohort experience a dose limiting toxicity (DLT) during the first treatment cycle, defined as any of the following that are both treatment-emergent and at least possibly related to ANG1005: i) Any Grade 3 or 4 nonhematologic toxicity, ii) Febrile neutropenia, iii) Grade 4 neutropenia of ≥7 days duration, and/or iv) Any Grade 4 thrombocytopenia, then dose escalation will stop and prior doses will be explored as the maximum tolerated dose (MTD), that dose-level at which ≤1 of 6 patients in a cohort develop an emergent DLT).

Once the MTD is established, approximately 14 patients will be enrolled at that dose-level in order to further assess the safety and tolerability of ANG1005, the PK profile of ANG1005 at the MTD, and the preliminary anti-tumor activity of ANG1005 in patients with malignant glioma.

Approximately 8 additional patients who are scheduled for debulking surgery for recurrent disease may be enrolled into a separate sub-study to obtain preliminary information about whether or not ANG1005 crosses the blood-brain barrier into malignant glioma tumors. These patients will receive ANG1005 prior to surgery at the dose level established to be safe and tolerable at that time and may continue to receive additional cycles of ANG1005 following surgery, if appropriate.

  Eligibility

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

Inclusion Criteria:

  1. Written informed consent
  2. Histologically confirmed malignant glioma
  3. Radiologically confirmed progression of malignant glioma
  4. Patients must, in the opinion of the investigator, be ineligible for current standard of care treatment
  5. No evidence of acute intracranial/intratumoral hemorrhage
  6. Male and female patients
  7. Age ≥18 years
  8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  9. An expected survival of at least 3 months
  10. Measurable disease according to Macdonald response criteria
  11. Male and female subjects who are not surgically sterile or post-menopausal must agree to use reliable methods of birth control for the duration of the study and for 90 days after the last dose of study drug administration; male partners of female subjects should use condoms for the duration of the study, and for 90 days after the last dose of study drug administration

Exclusion Criteria:

  1. Chemotherapy, radiotherapy (except palliative radiation delivered to <20% of bone marrow), or investigational agents within 4 weeks before the first dose of study drug. Biologic therapy (such as 13-cis-retinoic acid, thalidomide, tamoxifen, celebrex, erlotinib, imatinib, vorinostat, and lapatinib) and immunotherapy (such as interferon a or b, cdx-110 (EGFR vIII vaccine), interleukin 2, thalidomide) within 1 week before the first dose of study drug. Bevacizumab within 6 weeks before the first dose of study drug
  2. Pregnant or lactating females
  3. Any acute viral, bacterial, or fungal infection that requires parenteral therapy within 14 days prior to study treatment
  4. Known severe hypersensitivity to paclitaxel
  5. Severe toxicity with previous taxane treatment
  6. Patients being treated with P450 CYP 3A4 or CYP 2C8 enzyme-inducing anti-convulsant drugs within 14 days prior to treatment with study drug
  7. Patients with inadequate hematological, liver, and renal function
  8. Known or suspected acute or chronic active Hepatitis B, or Hepatitis C or HIV/AIDS
  9. Patients with unstable or uncompensated respiratory, cardiac, hepatic or renal disease or any other organ system dysfunction, medical condition, or laboratory abnormality which, in the opinion of the investigator, would either comprise the patient's safety or interfere with the evaluation of the test material
  10. Evidence of persistent Grade 2 or greater neurotoxicity
  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: NCT00539344

Locations
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, New York
Irving Comprehensive Cancer Center, Columbia University Medical Center
New York, New York, United States, 10032
United States, Texas
University of Texas, MD Anderson Cancer Center
Houston, Texas, United States, 77030
UT Health Science Center at the Cancer Therapy and Research Center (CTRC)
San Antonio, Texas, United States, 78229
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
Angiochem Inc
  More Information

Additional Information:
Publications:
Responsible Party: Jean-Paul Castaigne, MD - President & CEO, Angiochem Inc.
ClinicalTrials.gov Identifier: NCT00539344     History of Changes
Other Study ID Numbers: ANG1005-CLN-01, FDA
Study First Received: October 2, 2007
Last Updated: July 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Angiochem Inc:
Glioblastoma multiforme
Anaplastic astrocytoma
Anaplastic oligodendroglioma

Additional relevant MeSH terms:
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors

ClinicalTrials.gov processed this record on November 27, 2014