A Phase 1, Open-Label, Dose Escalation Study of ANG1005 in Patients With Advanced Solid Tumors and Metastatic Brain Cancer - Full Text View

Sponsor:	Angiochem Inc
Information provided by:	Angiochem Inc
ClinicalTrials.gov Identifier:	NCT00539383

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 solid tumors (with or without brain metastases). 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
Advanced Solid Tumors With and Without Brain Metastases	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 Advanced Solid Tumors and Metastatic Brain Cancer

Resource links provided by NLM:

MedlinePlus related topics: Brain Cancer Cancer

U.S. FDA Resources

Further study details as provided by Angiochem Inc:

Primary Outcome Measures:

To characterize the safety and tolerability of intravenously administered ANG1005 in patients with advanced solid tumors and metastatic brain cancer. [ Time Frame: On-going ] [ Designated as safety issue: Yes ]
To identify the maximum tolerated dose (MTD) of ANG1005 in patients with advanced solid tumors and metastatic brain cancer. [ 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 on the antitumor activity of ANG1005 in patients with advanced solid tumors with brain metastases. [ Time Frame: On-going ] [ Designated as safety issue: No ]

Enrollment:	56
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 solid tumors (with or without brain metastases). 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 or more patients 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 solid tumors (with or without brain metastases).

Eligibility

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

Criteria

Inclusion Criteria:

Written informed consent
Histologically or cytologically confirmed metastatic or advance-stage solid tumor that has progressed following standard therapy or for which, in the opinion of the Investigator, no standard effective therapy is available; patients without brain metastases may be enrolled into the dose-escalation part of the study
Patients enrolled into the expanded MTD cohort must have shown unequivocal evidence of brain metastases
Male and female patients.
Age ≥18 years
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
An expected survival of at least 3 months
Measurable disease according to RECIST criteria; patients with brain metastases must have at least one measurable lesion in the brain, according to RECIST criteria
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:

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
Pregnant or lactating females
Any acute viral, bacterial, or fungal infection that requires parenteral therapy within 14 days prior to study treatment
Known severe hypersensitivity to paclitaxel
Severe toxicity with previous taxane treatment
Treatment with P450 CYP 3A4 or CYP 2C8 enzyme-inducing anti-convulsant drugs within 14 days prior to treatment with study drug
Patients with inadequate hematological, liver, and renal function
Known or suspected acute or chronic active Hepatitis B, Hepatitis C, or HIV/AIDS
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
Evidence of persistent Grade 2 or greater neurotoxicity

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00539383

Locations

United States, Ohio
Gabrail Cancer Center
Canton, Ohio, United States, 44718
United States, Texas
University of Texas, MD Anderson Cancer Center
Houston, Texas, United States, 77030
UT Health Science Center, Cancer Therapy and Research Center
San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Angiochem Inc

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Jean-Paul Castaigne, MD - President & CEO, Angiochem Inc.
ClinicalTrials.gov Identifier:	NCT00539383 History of Changes
Other Study ID Numbers:	ANG1005-CLN-02, FDA
Study First Received:	October 3, 2007
Last Updated:	June 3, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Angiochem Inc:

Lung cancer
Breast cancer
Melanoma
Hepatocellular carcinoma
Brain metastases

Additional relevant MeSH terms:

Brain Neoplasms
Neoplasm Metastasis
Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site

Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplastic Processes
Pathologic Processes

ClinicalTrials.gov processed this record on May 22, 2012