Phase I Study of ABT-510 in Combination With Bevacizumab in Advanced Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
Phase I Study of ABT-510 in Combination With Bevacizumab in Advanced Solid Tumors
OBJECTIVES:
Primary
- Determine the recommended phase II dose for the combination of ABT-510 plus bevacizumab
in patients with advanced solid tumors.
- Evaluate dose-limiting toxicities and non dose-limiting toxicities of this combination.
Secondary
- Collect preliminary data on the clinical activity of this combination (tumor response
rate, progression-free survival, and rate of stable disease > 6 months).
OUTLINE: This is a dose-escalation study. Patients are sequentially enrolled with the first
9-18 patients assigned to part 1 and the next 20 patients assigned to part 2 of the study.
- Part 1: Patients receive ABT-510 subcutaneously (SC) twice daily on days 1-28 and
bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.
Cohorts of patients receive escalating doses of ABT-510 and bevacizumab until the
recommended phase II dose is determined. Patients in part 2 are treated at the recommenced
phase II dose.
- Part 2: The first 10 patients are assigned to group 1. The next 10 patients are
assigned to group 2.
- Group 1: Patients receive ABT-510 SC twice daily beginning on day 1 and
bevacizumab IV once every 14 days beginning on day 15.
- Group 2: Patients receive ABT-510 SC twice daily beginning on day 15 and
bevacizumab IV once every 14 days beginning on day 1.
In both groups, treatment continues in the absence of disease progression or unacceptable
toxicity.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 38 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed advanced solid tumor
- Refractory to standard therapy or for which there is no standard therapy
- No known brain metastases
- Patients with primary malignancies known to metastasize to the brain (such as
lung cancer, breast cancer, renal cell cancer, sarcoma, carcinoma of unknown
primary, melanoma, or head and neck cancers) or patients with symptoms of brain
metastases should have a brain MRI within 28 days of enrollment to confirm the
absence of CNS metastases
- Contrast CT scan is acceptable for patients who are unable to undergo a
brain MRI
- No squamous cell carcinoma of the lung
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- PT/INR/PTT ≤ 1.2 times ULN
- AST/ALT ≤ 2.5 times ULN (5 times ULN if known hepatic metastases)
- Urine protein:creatinine ≤ 1.0 (spot urine sample)
- Creatinine clearance ≥ 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during the study and for up to 4
months after study completion
- No New York Heart Association class III or IV heart disease
- No angina requiring nitrates
- No myocardial infarction in the past 6 months
- No cerebrovascular accident or transient ischemic attack in the past 6 months
- No thrombosis within 3 months
- No poorly controlled hypertension (i.e., blood pressure > 160/100 mm Hg)
- No ventricular arrhythmia requiring medication
- No poorly controlled or clinically significant atherosclerotic vascular disease
- No coagulopathy
- No presence of bleeding diathesis
- No non-healing wounds
- No gastrointestinal (GI) perforation within past 6 months
- No acute GI bleed requiring transfusion or invasive intervention within the past 6
months
- No hemoptysis greater than 1 tablespoon within 6 months
- No other major bleeding event
- No history of intra-abdominal fistula or abscess within the past 6 months
- No uncontrolled intercurrent illness
- No history of intolerance to bevacizumab or ABT-510
- No ongoing or active infection
- No psychiatric illness or social situations that would limit safety or compliance
with study requirements
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 3 months
after study participation
PRIOR CONCURRENT THERAPY:
- No angioplasty in the past 6 months
- No cardiac or vascular stenting in the past 6 months
- Patients with prostate cancer who are already receiving androgen deprivation therapy
(i.e., leuprolide or goserelin) for longer than 3 months may continue on this therapy
during the study
- No major surgery within past 28 days
- No other investigational agents within the past 28 days
- No chemotherapy for cancer within past 21 days
- No biologic therapy for cancer within past 21 days
- No radiation therapy within past 21 days
- No hormonal therapy within past 21 days
- No minor surgical procedures within past 14 days
- Initiation or adjustment of blood pressure (BP) medication is permitted prior to
study entry
- Must have 3 consecutive BP readings less than 150/90 mm Hg
- Each reading must be separated by a minimum of 24 hours
- No concurrent use of therapeutic anticoagulation
- Prophylactic low-dose anticoagulation for indwelling catheter is permitted
provided PT/PTT is within normal limits
- No use of antiplatelet agents other than aspirin (< 325 mg/day) or standard dose
nonsteroidal anti-inflammatory drugs
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Herbert I. Hurwitz, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Duke Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000449951
NCT ID:
NCT00276562
Start Date:
May 2005
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
