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

NCT01199367 | Terminated Phase 1

• 1 other identifier: 2450-US-002
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 5

Brief Summary

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. This study was terminated in Phase 1 and never proceeded to the Phase 2 portion of the study.

Conditions

Breast Cancer

Keywords

advanced or metastatic breast cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  30 Days

Secondary Outcomes (1)

• To determine the PK profile of KW-2450, lapatinib, and letrozole when administered together

  1 year (or until PD)

Study Arms (1)

Dose escallation

EXPERIMENTAL

Drug: KW-2450 in combination with lapatinib and letrozole

Interventions

KW-2450 in combination with lapatinib and letrozole DRUG

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.

Also known as: KW-2450 lapatinib and letrozole

Dose escallation

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Type 1 diabetes or uncontrolled Type 2 diabetes
• Subjects showing clinical evidence or with a history of cataract(s), proliferate retinopathy or significant macular edema
• Subjects with abnormal free T4 values and a history or evidence of thyroid disease
• Subjects who are unable or unwilling to take metformin
• Uncontrolled intercurrent illness
• Known or suspected human immunodeficiency virus (HIV) infection or hepatitis B or C
• Subjects with inflammatory diseases of the gastrointestinal tract
• 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;
• Subjects with extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor
• A history of prior treatment with other agents specifically targeting IGFRs
• Subjects who require pharmacological doses of glucocorticoids beyond replacement doses. The use of topical, intra-ocular or inhalation glucocorticoids is permitted

Sponsors & Collaborators

• Kyowa Kirin Co., Ltd.: lead
• Kyowa Hakko Kirin Pharma, Inc.: collaborator

Study Sites (5)

Breastlink Research Group

Long Beach, California, 90250, United States

Location

Associates in Hematology-Oncology

Los Angeles, California, 90057, United States

Location

Sylvester Comprehensive Cancer Center

Deerfield Beach, Florida, 33136, United States

Location

Clinical Oncology Associates

Farmington Hills, Michigan, 48336, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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)

  RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

KW-2450; Lapatinib; Letrozole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Michael Kurman, MD

  Kyowa Hakko Kirin Pharma, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2010
• First Posted: September 10, 2010
• Study Start: December 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: April 25, 2024

Record last verified: 2024-04

Locations

US (5)