A Phase 1, Open-Label, Dose Escalation Study of ANG1005 in Patients With Advanced Solid Tumors and Metastatic Brain Cancer
18 Years
N/A
Both
Advanced Solid Tumors With and Without Brain Metastases
Trial Information
A Phase 1, Open-Label, Dose Escalation Study of ANG1005 in Patients With Advanced Solid Tumors and Metastatic Brain Cancer
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).
Inclusion Criteria:
1. Written informed consent
2. 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
3. Patients enrolled into the expanded MTD cohort must have shown unequivocal evidence
of brain metastases
4. Male and female patients.
5. Age ≥18 years
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
7. An expected survival of at least 3 months
8. Measurable disease according to RECIST criteria; patients with brain metastases must
have at least one measurable lesion in the brain, according to RECIST criteria
9. 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. Treatment 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, 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label
Outcome Measure:
To characterize the safety and tolerability of intravenously administered ANG1005 in patients with advanced solid tumors and metastatic brain cancer.
Outcome Time Frame:
On-going
Safety Issue:
Yes
Authority:
United States: Food and Drug Administration
Study ID:
ANG1005-CLN-02
NCT ID:
NCT00539383
Start Date:
October 2007
Completion Date:
March 2010
Related Keywords:
- Advanced Solid Tumors With and Without Brain Metastases
- Lung cancer
- Breast cancer
- Melanoma
- Hepatocellular carcinoma
- Brain metastases
- Brain Neoplasms
- Neoplasm Metastasis
- Neoplasms
Name | Location |
|---|---|
| Gabrail Cancer Center | Canton, Ohio 44718 |
| University of Texas, MD Anderson Cancer Center | Houston, Texas 77030 |
| UT Health Science Center, Cancer Therapy and Research Center | San Antonio, Texas 78229 |
