A Phase I Study of ABT-510 in Combination With Bevacizumab in Advanced Solid Tumors

NCT00586092 | Completed Phase 1

• 1 other identifier: Pro00008797
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine the recommended Phase II dose for the combination of ABT-510 plus bevacizumab in patients with advanced solid tumors and to evaluate dose limiting toxicities and non-dose limiting toxicities of this combination. The secondary objectives are to collect preliminary data on the effect of the combination of ABT-510 plus bevacizumab versus each agent individually on dermal wound angiogenesis in a skin biopsy and to collect preliminary data on the clinical activity of this combination (tumor response rate, progression-free survival, rate of stable disease \> 6 months).

Conditions

Solid Tumors

Keywords

Phase I; Phase 1; avastin; bevacizumab; ABT-510; solid tumors; angiogenesis

Outcome Measures

Primary Outcomes (1)

• To determine the recommended Phase II dose for the combination of ABT-510 plus bevacizumab

  Each Cycle (28-days)

Secondary Outcomes (1)

• To collect preliminary data on the clinical activity of this combination (tumor response rate, progression-free survival, rate of stable disease > 6 months).

  Each Cycle (28-days)

Study Arms (1)

1

OTHER

This trial employs a phase I design with a dose escalation stage (stage I) and an expansion stage (stage 2) to better describe the tolerability of this combination and the effect of this combination on several biomarkers. In this second stage there will be two groups, each with ten patients, to better describe the tolerability of the bevacizumab/ABT-510 combination and the effect of this combination on several biomarkers. The primary objective of this study is to estimate the MTD/recommended phase II dose regimen. All other objectives are exploratory in nature.

Drug: bevacizumab, ABT-510

Interventions

bevacizumab, ABT-510 DRUG

* Stage 1 (Cohorts -1, 2, 2, 3) ABT-510: 25, 50, 50, 100 mg SC BID\*, bevacizumab: 5, 5, 10, 10 mg/kg IV every 14 days\* * Stage 2 (RPTD) ABT-510: X mg SC BID\*\*, bevacizumab: Y mg/kg IV every 14 days\*\* * Stage I is the dose escalation stage. Stage II will include an additional 20 patients (10 patients in each group) enrolled at the RPTD in two different schedules to better assess safety and biomarker correlates. * \*Both agents begin on Day 1 of Cycle 1. * \*\*At the RPTD, ½ the patients will begin ABT-510 (Dose X) on Day 1 and bevacizumab (Dose Y) on Day 15 and the other ½ of the patients will begin bevacizumab on Day 1 and ABT-510 on Day 15. This will allow for a collection of some preliminary data of wound angiogenesis effects of ABT-510 alone versus the combination and bevacizumab alone versus the combination.

Also known as: avastin

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of advanced solid tumor refractory to standard therapy or for whom there is no standard therapy.
• Patients must not have had radiation therapy, hormonal therapy, biologic therapy or chemotherapy for cancer within the 21 days prior to study Day 1. Patients must not have had major surgery within the 28 days prior to study Day 1 or minor surgical procedures within the 14 days prior to study Day 1.
• Age \> 18 years.
• ECOG performance status of 0-1 (see Appendix A).
• Patients must have normal organ and marrow function as defined below:
• hemoglobin \> 9.0g/dL; absolute neutrophil count \> 1,500/μl; platelets \> 100,000/μl; total bilirubin \< 1.5 X upper limit of normal (ULN), AST(SGOT)/ALT(SGPT) \< 2.5 X ULN, \< 5 X ULN if known hepatic metastases; Urine protein:creatinine ratio \< 1.0; creatinine clearance \> 50 mL/min/1.73 m2; PT/INR/PTT \< 1.2X ULN
• The effect of the investigational drugs on the developing human fetus is not known, but these drugs are likely to be embryo- and feto- toxic. Women of child-bearing potential must agree to use adequate contraception (either surgical sterilization; approved hormonal contraceptives such as birth control pills, Depo-Provera, or Lupron Depot; barrier methods such as condom or diaphragm along with spermicide; or an IUD). Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician and study PI immediately. Patients should be willing to use adequate contraception for three months following discontinuation of study drug.
• The patient is able to self-administer or has a caregiver who can reliably administer subcutaneous injections.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients who have had radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for cancer within the 21 days prior to Day 1 of the study. Patients with prostate cancer who are already receiving androgen deprivation therapy (ie. leuprolide or goserelin) for longer than 3 months may continue on this therapy during the study.
• Patients who have received any other investigational agents within the 28 days prior to Day 1 of the study.
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis, the uncertain risk of this regimen on tumor bleeding, and because these patients often develop progressive neurological dysfunction that would confound the evaluation of neurologic and other adverse events. 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, and 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 is acceptable for patients who are unable to undergo a brain MRI.
• Patients with poorly controlled or clinically significant atherosclerotic vascular disease including CHF NY Heart Class \> 2 (see Appendix B); angina requiring nitrates; MI, CVA, TIA, angioplasty, cardiac or vascular stenting in the past 6 months; or ventricular arrhythmia requiring medication.
• History of intolerance of prior treatment with bevacizumab or ABT-510. Prior treatment with these agents is otherwise permitted.
• Poorly controlled hypertension (\> 160/100). Initiation or adjustment of BP medication is permitted prior to study entry provided that patient has 3 consecutive BP readings less than 150/90 mmHg each separated by a minimum of 24 hours. These readings should be collected prior to first skin biopsy.
• History of thrombosis within 3 months prior to enrollment or current use of therapeutic anticoagulation. Prophylactic low-dose anticoagulation for indwelling catheters is permitted; PT/PTT must be within normal limits.
• Use of antiplatelet agents other than aspirin (\< 325 mg/day) or standard dose NSAIDs.
• Presence of bleeding diathesis, coagulopathy, or major bleeding event such as an acute GI bleed requiring transfusion or invasive intervention or hemoptysis greater than 1 tablespoon within 6 months prior to Day 1 of the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit safety or compliance with study requirements. In addition, patients with non-healing wounds will not be eligible for this study.
• Pregnant women are excluded from this study because the investigational drugs have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these drugs, breastfeeding should be discontinued if the mother is treated on this study.
• Patients with squamous cell carcinoma of the lung.
• History of intra-abdominal fistula, gastrointestinal perforation or intr-abdominal abscess within 6 months prior to Day 1.

Sponsors & Collaborators

• Herbert Hurwitz: lead
• Genentech, Inc.: collaborator
• Abbott: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Interventions

Bevacizumab; NAc-Sar-Gly-Val-(d-allo-Ile)-Thr-Nva-Ile-Arg-ProNEt

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Herb Hurwitz, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: January 4, 2008
• Study Start: September 1, 2005
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: April 8, 2013

Record last verified: 2013-04

Locations

US (1)