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

This study has been completed.
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT00645177
First received: March 24, 2008
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: ABT-869
Drug: paclitaxel
Drug: Placebo for ABT-869
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Radiographic evaluation every 3 months, clincial evaluation monthly ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Subject death ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: July 2008
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00645177

Locations
United States, California
Site Reference ID/Investigator# 8352
San Francisco, California, United States, 94115
United States, Illinois
Site Reference ID/Investigator# 6920
Harvey, Illinois, United States, 60426
Mexico
Site Reference ID/Investigator# 10181
Durango, DGO., Mexico, CP 34000
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Genentech, Inc.
Investigators
Study Director: Justin L. Ricker, MD AbbVie
  More Information

No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT00645177     History of Changes
Other Study ID Numbers: M10-265, 2007-005905-23
Study First Received: March 24, 2008
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration
Mexico: Ministry of Health

Keywords provided by AbbVie:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 29, 2014