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

A Phase 2 Randomized, Placebo-Controlled, Double-Blind Study of ABT-869 in Combination With Paclitaxel Versus Paclitaxel Alone as First-line Treatment in Subjects With Locally Recurrent or Metastatic Breast Cancer

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: ABT-869; Drug: paclitaxel; Drug: Placebo for ABT-869

Detailed Description

Only the open-label lead-in portion of the study was enrolled (n=10). The randomized portion was not initiated. N = approximately 102 (90 randomized in a 1:1 ratio in Phase 2, approximately 6-12 enrolled in open-label lead-in to assess the tolerability of the combination) Phase 2, randomized, placebo-controlled, double-blind, multi-center study of the efficacy and tolerability of the ABT-869 + paclitaxel versus placebo for ABT-869 + paclitaxel in subjects with documented metastatic breast cancer in the first line metastatic therapy setting. An 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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • Durango, DGO., Mexico, CP 34000
    • Site Reference ID/Investigator# 10181
• United States
  • California
    • San Francisco, California, United States, 94115
      • Site Reference ID/Investigator# 8352
  • Illinois
    • Harvey, Illinois, United States, 60426
      • Site Reference ID/Investigator# 6920

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; 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; 0.20 mg/kg (or dose from Lead-in) QD, tablets taken orally days 1-28 of every 28-day cycle; Drug: paclitaxel; 90 mg/m2 IV infusion over 1 hour, weekly every 3 out of 4 weeks
Placebo Comparator: B; 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; 90 mg/m2 IV infusion over 1 hour, weekly every 3 out of 4 weeks; Drug: Placebo for ABT-869; 0.20 mg/kg (or dose from Lead-in) QD, tablets taken orally days 1-28 of every 28-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	Radiographic evaluation every 3 months, clincial evaluation monthly

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	Subject death

Collaborators and Investigators

• Sponsor: AbbVie (prior sponsor, Abbott)
• Collaborators: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: March 24, 2008
• First Submitted That Met QC Criteria: March 26, 2008
• First Posted (Estimate): March 27, 2008

Study Record Updates

• Last Update Posted (Estimate): January 29, 2013
• Last Update Submitted That Met QC Criteria: January 23, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: M10-265; 2007-005905-23 (EudraCT Number)