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

Primary Purpose

Breast Cancer

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

KW-2450 in combination with lapatinib and letrozole

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring advanced or metastatic breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

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

Exclusion Criteria

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

Sites / Locations

Breastlink Research Group
Associates in Hematology-Oncology
Sylvester Comprehensive Cancer Center
Clinical Oncology Associates
MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dose escallation

Arm Description

Outcomes

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.

Secondary Outcome Measures

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

Full Information

NCT ID

NCT01199367

First Posted

September 8, 2010

Last Updated

April 4, 2014

Sponsor

Kyowa Hakko Kirin Pharma, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01199367

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2014

Overall Recruitment Status

Terminated

Why Stopped

The results of the dose escalation phase did not identify a well-tolerated dose that would permit further study in Phase 2.

Study Start Date

December 2010 (undefined)

Primary Completion Date

December 2012 (Actual)

Study Completion Date

December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Kyowa Hakko Kirin Pharma, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

advanced or metastatic breast cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

11 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose escallation

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

KW-2450 in combination with lapatinib and letrozole

Other Intervention Name(s)

KW-2450 lapatinib and letrozole

Intervention Description

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.

Primary Outcome Measure Information:

Title

Time Frame

30 Days

Secondary Outcome Measure Information:

Title

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

Time Frame

1 year (or until PD)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria 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 Exclusion Criteria 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Kurman, MD

Organizational Affiliation

Kyowa Hakko Kirin Pharma, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Breastlink Research Group

City

Long Beach

State/Province

California

ZIP/Postal Code

90250

Country

United States

Facility Name

Associates in Hematology-Oncology

City

Los Angeles

State/Province

California

ZIP/Postal Code

90057

Country

United States

Facility Name

Sylvester Comprehensive Cancer Center

City

Deerfield Beach

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Clinical Oncology Associates

City

Farmington Hills

State/Province

Michigan

ZIP/Postal Code

48336

Country

United States

Facility Name

MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Citations:

Citation

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)

Results Reference

result

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

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