Phase 2 Study of ABT-869 in Combination With Paclitaxel Versus Paclitaxel Alone to Treat Metastatic Breast Cancer

NCT00645177 | Completed Phase 2

• 2 other identifiers: M10-2652007-005905-23
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 3

Brief Summary

The purpose of this study is to determine the effect of ABT-869 plus paclitaxel compared to paclitaxel alone on disease progression in metastatic breast cancer.

Conditions

Metastatic Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Radiographic evaluation every 3 months, clincial evaluation monthly

Secondary Outcomes (1)

• Overall survival

  Subject death

Study Arms (2)

A

ACTIVE COMPARATOR

In study, this arm is a randomized (blinded) to ABT-869 arm plus paclitaxel. Note: Prior to randomization, approximately 6-12 subjects will be enrolled in open-label lead-in to assess the tolerability of the combination. The initial open-label, lead-in cohort of six subjects will be monitored for 2 cycles (8 weeks) to assess the PK interactions and the safety of the combination of 0.20 mg/kg QD ABT-869 and paclitaxel (90 mg/m2). Enrollment into the randomized portion will begin after a cohort has completed two cycles (8 weeks) of therapy and no toxicities prohibit the cohort from continuing on to Cycle 3. Alternative doses may be explored based on the tolerability of the combination

Drug: ABT-869; Drug: paclitaxel

B

PLACEBO COMPARATOR

In study, this arm is a randomized (blinded) to placebo for ABT-869 plus paclitaxel arm. Note: Prior to randomization, approximately 6-12 subjects will be enrolled in open-label lead-in to assess the tolerability of the combination. The initial open-label, lead-in cohort of six subjects will be monitored for 2 cycles (8 weeks) to assess the PK interactions and the safety of the combination of 0.20 mg/kg QD ABT-869 and paclitaxel (90 mg/m2). Enrollment into the randomized portion will begin after a cohort has completed two cycles (8 weeks) of therapy and no toxicities prohibit the cohort from continuing on to Cycle 3. Alternative doses may be explored based on the tolerability of the combination

Drug: paclitaxel; Drug: Placebo for ABT-869

Interventions

ABT-869 DRUG

0.20 mg/kg (or dose from Lead-in) QD, tablets taken orally days 1-28 of every 28-day cycle

A

paclitaxel DRUG

90 mg/m2 IV infusion over 1 hour, weekly every 3 out of 4 weeks

A; B

Placebo for ABT-869 DRUG

0.20 mg/kg (or dose from Lead-in) QD, tablets taken orally days 1-28 of every 28-day cycle

B

Eligibility Criteria

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

You may qualify if:

• Subject must be female and \> 18 years of age.
• Subject must be diagnosed with adenocarcinoma of the breast.
• Subject must have metastatic disease or locally recurrent disease that is not amenable to surgical resection with curative intent.
• No prior chemotherapy for locally recurrent or metastatic breast cancer.
• At least 12 months since prior adjuvant or neoadjuvant chemotherapy (including prior taxane therapy and prior anti-angiogenic therapy \[i.e. bevacizumab or a TKI\]).
• No HER-2 -over-expression (3+) breast cancer (unless treated with trastuzumab or lapatinib).
• Subject has measurable disease by RECIST criteria (randomized portion only).
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1.
• Subject must have adequate bone marrow, renal and hepatic function.
• Subject must have PTT \< 1.5 x ULN and INR \< 1.5.

You may not qualify if:

• Subject has received anti-cancer therapy (other than chemotherapy) including investigational agents, or biologic therapy within 21 days or within a period defined by 5 half lives, whichever is shorter, prior to Study Day 1.
• Subject has not recovered to less than or equal to grade 1 clinically significant adverse effects/toxicities of the previous therapy.
• Subject has received radiation therapy within 14 days of Study Day 1.
• Subject has received anti-cancer hormonal therapy within 14 days of Study Day 1.
• Subject has undergone major surgery within 21 days of Study Day 1.
• The subject has untreated brain or meningeal metastases.
• Subject is receiving therapeutic anticoagulation therapy.
• Subject has a history of or currently exhibits clinically significant cancer related events of bleeding (e.g., hemoptysis).
• Subject currently exhibits symptomatic or persistent, uncontrolled hypertension.
• Subject has a history of myocardial infarction, stroke, or transient ischemic attack (TIA) within 6 months of study day 1.
• Subject has a documented left ventricular (LV) ejection fraction \< 50%
• Subject has known autoimmune disease with renal involvement.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead
• Genentech, Inc.: collaborator

Study Sites (3)

Site Reference ID/Investigator# 8352

San Francisco, California, 94115, United States

Location

Site Reference ID/Investigator# 6920

Harvey, Illinois, 60426, United States

Location

Site Reference ID/Investigator# 10181

Durango, DGO., CP 34000, Mexico

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

linifanib; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Justin L. Ricker, MD

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2008
• First Posted: March 27, 2008
• Study Start: July 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: January 29, 2013

Record last verified: 2013-01

Locations

US (2); ME (1)