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

Recurrent or Progressive Malignant Glioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00539344
• Other study ID #: ANG1005-CLN-01
• Secondary ID: FDA
• Status: Completed
• Phase: Phase 1
• First received: October 2, 2007
• Last updated: July 30, 2014
• Start date: October 2007
• Est. completion date: March 2010

Study information

• Verified date: July 2014
• Source: Angiochem Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Glioma
• Recurrent or Progressive Malignant Glioma

Intervention

Drug:
• ANG1005
IV infusion once every 21 days

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Henry Ford Health System	Detroit	Michigan
United States	University of Texas, MD Anderson Cancer Center	Houston	Texas
United States	Irving Comprehensive Cancer Center, Columbia University Medical Center	New York	New York
United States	UT Health Science Center at the Cancer Therapy and Research Center (CTRC)	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Angiochem Inc

Country where clinical trial is conducted

United States, 

References & Publications (1)

Drappatz J, Brenner A, Wong ET, Eichler A, Schiff D, Groves MD, Mikkelsen T, Rosenfeld S, Sarantopoulos J, Meyers CA, Fielding RM, Elian K, Wang X, Lawrence B, Shing M, Kelsey S, Castaigne JP, Wen PY. Phase I study of GRN1005 in recurrent malignant glioma — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To characterize the safety and tolerability of intravenously administered ANG1005 in patients with malignant glioma.		On-going	Yes
Primary	To identify the maximum tolerated dose (MTD) of ANG1005 in patients with malignant glioma.		End of dose escalation	Yes
Secondary	To examine the pharmacokinetics (PK) of ANG1005.		End of study	No
Secondary	To confirm the safety and tolerability of ANG1005 at the MTD.		End of dose escalation	Yes
Secondary	To assess the immunogenicity of ANG1005.		End of study	No
Secondary	To obtain preliminary information about the antitumor activity of ANG1005 in patients with malignant glioma.		On-going	No
Secondary	To obtain preliminary information about whether or not ANG1005 crosses the blood- brain barrier into malignant glioma tumors (Sub-study).		On-going	No

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