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Safety, Tolerability, and Efficacy Study in Subjects With Advanced or Metastatic Breast Cancer

This study has been terminated.
(The results of the dose escalation phase did not identify a well-tolerated dose that would permit further study in Phase 2.)
Sponsor:
Information provided by (Responsible Party):
Kyowa Hakko Kirin Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT01199367
First received: September 8, 2010
Last updated: January 10, 2013
Last verified: January 2013
History of Changes
  Purpose

This study will determine the highest dose of KW-2450 in combination with lapatinib and letrozole that can be administered safely to subjects with advanced or metastatic breast cancer and to evaluate its effectiveness.


Condition Intervention Phase
Breast Cancer
 Drug: KW-2450 in combination with lapatinib and letrozole
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of KW-2450 in Combination With Lapatinib and Letrozole in Subjects With Advanced or Metastatic Breast Cancer Whose Tumors Overexpress HER2

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Kyowa Hakko Kirin Pharma, Inc.:

Primary Outcome Measures:
  • To establish the safety, tolerability, and recommended Phase 2 dose of KW-2450 administered in combination with lapatinib and letrozole in subjects with previously treated or untreated advanced breast cancer. [ Time Frame: 30 Days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the PK profile of KW-2450, lapatinib, and letrozole when administered together [ Time Frame: 1 year (or until PD) ] [ Designated as safety issue: Yes ]

Enrollment: 11
Study Start Date: December 2010
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose escallation Drug: KW-2450 in combination with lapatinib and letrozole
Three subjects will be assigned to each of 4 sequential cohorts. Dose escalation may proceed once at least 3 subjects have completed 30 days of study treatment. Subjects who withdraw prior to completing Day 30 for reasons other than DLT will be replaced. If a DLT is observed, additional subjects may be enrolled so that up to 6 subjects are enrolled at that dose level.
Other Name: KW-2450 lapatinib and letrozole

Detailed Description:

This open-label, sequential, ascending, multi-dose, Phase 1/2 study will enroll up to 198 post-menopausal subjects with advanced or metastatic breast cancer whose tumors overexpress HER2. Subjects at each dose level will receive KW-2450 orally, on a continuous daily schedule in combination with lapatinib and letrozole.

In the Phase 1 portion of the study, dose escalation may proceed once ≥ 3 subjects have completed Day 30. The safety of each dose level will be established prior to enrollment of subjects in the next dose level. Dose escalation will proceed sequentially. Up to 6 subjects may be enrolled at each dose level. Enrollment will proceed until the MTD has been established or the highest dose level has been reached.

The Phase 2 portion of the trial will enroll 168 additional subjects. The dose level will be based on overall safety and tolerability assessments from the Phase 1 portion of the study. The subjects will be randomized into two treatment arms (1) Arm A, KW-2450 plus lapatinib plus letrozole: (2) Arm B, lapatinib plus letrozole.

  Eligibility

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

Inclusion Criteria

  1. Histopathologically or cytologically confirmed, advanced or metastatic breast cancer (stage IIIb, IIIc or IV disease) including inflammatory breast cancer or inoperable locally advanced disease.
  2. Documented ErbB2 overexpression
  3. Estrogen receptor positive (ER+) and/or progesterone positive (PgR+) tumors
  4. Measurable or non-measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria
  5. A life expectancy of > 3 months for Phase 1 and > 6 months for Phase 2
  6. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2 at study entry in Phase 1 and ≤ 1 in Phase 2;
  7. Normal cardiac ejection fraction
  8. Adequate hematologic, hepatic and renal function
  9. Post-menopausal female (defined as the absence of a menstrual cycle for at least 12 consecutive months) or male subjects ≥ 18 years of age.
  10. Sign an IRB or EC approved informed consent

Exclusion Criteria

  1. Type 1 diabetes or uncontrolled Type 2 diabetes
  2. Subjects showing clinical evidence or with a history of cataract(s), proliferate retinopathy or significant macular edema
  3. Subjects with abnormal free T4 values and a history or evidence of thyroid disease
  4. Subjects who are unable or unwilling to take metformin
  5. Uncontrolled intercurrent illness
  6. Known or suspected human immunodeficiency virus (HIV) infection or hepatitis B or C
  7. Subjects with inflammatory diseases of the gastrointestinal tract
  8. History of other malignancy. Subjects who have been disease free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible;
  9. Subjects with extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor
  10. A history of prior treatment with other agents specifically targeting IGFRs
  11. Subjects who require pharmacological doses of glucocorticoids beyond replacement doses. The use of topical, intra-ocular or inhalation glucocorticoids is permitted
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01199367

Locations
United States, California
Breastlink Research Group
Long Beach, California, United States, 90250
Associates in Hematology-Oncology
Los Angeles, California, United States, 90057
United States, Florida
Sylvester Comprehensive Cancer Center
Deerfield Beach, Florida, United States, 33136
United States, Michigan
Clinical Oncology Associates
Farmington Hills, Michigan, United States, 48336
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Kyowa Hakko Kirin Pharma, Inc.
Investigators
Study Director: Michael Kurman, MD Kyowa Hakko Kirin Pharma, Inc.
  More Information

Publications:
Dickson MA, P. LoRusso P, E. A. Sausville EA, Rao N, Kobayashi E, Kurman MR, Akinaga S, Schwartz GK. Open-label, sequential, ascending, multi-dose, phase I study of KW-2450 as monotherapy in subjects with previously treated advanced solid tumors. J Clin Oncol 29: 2011 (suppl; abstr 3078)

Responsible Party: Kyowa Hakko Kirin Pharma, Inc.
ClinicalTrials.gov Identifier: NCT01199367     History of Changes
Other Study ID Numbers: 2450-US-002
Study First Received: September 8, 2010
Last Updated: January 10, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Kyowa Hakko Kirin Pharma, Inc.:
advanced or metastatic breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Lapatinib
 Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on May 23, 2013