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Lapatinib and Tamoxifen in Treating Patients With Advanced or Metastatic Breast Cancer (LAPATAM)

Primary Purpose

Breast Cancer

Status

Unknown status

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

lapatinib ditosylate

tamoxifen citrate

pharmacological study

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring male breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, recurrent breast cancer

Eligibility Criteria

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

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed advanced or metastatic breast cancer
- Progressive disease after aromatase inhibitor therapy
Hormone receptor status:
- Estrogen receptor- and/or progesterone receptor-positive tumor
Patients with stable brain metastases (i.e., no neurological symptoms and no corticosteroid treatment) are eligible

PATIENT CHARACTERISTICS:

Male or female
Menopausal status not specified
ECOG performance status 0-2
Life expectancy ≥ 12 weeks
Neutrophil count > 1,500/mm³
Platelet count > 100,000/mm³
AST and/or ALT < 3 times upper limit of normal (ULN)
Creatinine < 1.5 times ULN
Bilirubin < 1.5 times ULN
Clinically normal cardiac function (i.e., LVEF normal by MUGA or ECHO)
No current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic live disease)
No ischemic heart disease within the past 6 months
Normal 12-lead ECG
No active or uncontrolled infections
No serious illnesses or medical conditions, including any of the following:
- Hypercalcemia
- Malabsorption syndrome
- Chronic alcohol abuse
- Hepatitis
- HIV
- Cirrhosis
Able to swallow and retain oral medication
No psychological, familial, sociological, or geographical condition potentially hampering study compliance
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after completion of study treatment

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 2 days since prior and no concurrent inducers or inhibitors of CYP3A4, including any of the following:
- Rifabutin
- Clarithromycin
- Cyclosporine
- Voriconazole
- Fluoxetine
- Paroxetine
- Midazolam
- Isoniazid
- Dihydralazine
- Digitoxin
- Coumadin
- Phenytoin
- Verapamil
- Diltiazem
- Herbal constituents (e.g., bergamottin and glabridin)
At least 2 weeks since prior aromatase inhibitor
- Aromatase inhibitors in the adjuvant and/or metastatic setting allowed
At least 1 year since prior tamoxifen citrate
No other concurrent anticancer therapy or investigational agents

Sites / Locations

Centre Regional Rene Gauducheau

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Tamoxifen-lapatinib

Lapatinib-tamoxifen

Arm Description

Tamoxifen alone at cycle 1 and as of cycle 2 in combination with Lapatinib.

Lapatinib will be given alone for 2 weeks during cycle 1. As of cycle 2, you will receive the combined treatment Lapatinib and Tamoxifen

Outcomes

Primary Outcome Measures

Pharmacokinetic profile of lapatinib ditosylate and tamoxifen citrate alone and in combination

Secondary Outcome Measures

Safety

Relationship between drug exposure and adverse events or biological modifications

Response in patients with measurable disease

Full Information

NCT ID

NCT00424164

First Posted

January 16, 2007

Last Updated

June 18, 2013

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

1. Study Identification

Unique Protocol Identification Number

NCT00424164

Brief Title

Lapatinib and Tamoxifen in Treating Patients With Advanced or Metastatic Breast Cancer

Acronym

LAPATAM

Official Title

Pharmacokinetics Study of Combined Treatment Lapatinib and Tamoxifen in Advanced/Metastatic Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

June 2013

Overall Recruitment Status

Unknown status

Study Start Date

November 2006 (undefined)

Primary Completion Date

June 2009 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

4. Oversight

5. Study Description

Brief Summary

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving lapatinib together with tamoxifen may be an effective treatment for breast cancer. PURPOSE: This randomized phase I trial is studying the side effects of lapatinib and tamoxifen in treating patients with advanced or metastatic breast cancer.

Detailed Description

OBJECTIVES: Primary Determine the pharmacokinetics of lapatinib ditosylate and tamoxifen citrate in patients with advanced or metastatic breast cancer. Secondary Assess the safety of this regimen in these patients. Determine any relationship between drug exposure and adverse events or biological modifications of this regimen in these patients. Assess the antitumor activity of this regimen in patients with measurable disease. OUTLINE: This is an open-label, randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral tamoxifen citrate on days 1-28 of course 1. In all subsequent courses, patients receive oral tamoxifen citrate and oral lapatinib ditosylate on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive oral lapatinib ditosylate on days 1-14 of course 1. In all subsequent courses, patients receive oral lapatinib ditosylate and oral tamoxifen citrate on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. In both treatment arms, blood is collected periodically during courses 1 and 2 for pharmacokinetic studies. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

6. Conditions and Keywords

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

Breast Cancer

Keywords

male breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, recurrent breast cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Tamoxifen-lapatinib

Arm Type

Experimental

Arm Description

Tamoxifen alone at cycle 1 and as of cycle 2 in combination with Lapatinib.

Arm Title

Lapatinib-tamoxifen

Arm Type

Experimental

Arm Description

Lapatinib will be given alone for 2 weeks during cycle 1. As of cycle 2, you will receive the combined treatment Lapatinib and Tamoxifen

Intervention Type

Drug

Intervention Name(s)

lapatinib ditosylate

Intervention Type

Drug

Intervention Name(s)

tamoxifen citrate

Intervention Type

Other

Intervention Name(s)

pharmacological study

Primary Outcome Measure Information:

Title

Pharmacokinetic profile of lapatinib ditosylate and tamoxifen citrate alone and in combination

Time Frame

maximum 24h after the dose administered on Day 28

Secondary Outcome Measure Information:

Title

Safety

Time Frame

until disease progression or until the start of another treatment (average 2 months)

Title

Relationship between drug exposure and adverse events or biological modifications

Time Frame

until disease progression or until the start of another treatment (average 2 months)

Title

Response in patients with measurable disease

Time Frame

until disease progression or until the start of another treatment (average 2 months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed advanced or metastatic breast cancer Progressive disease after aromatase inhibitor therapy Hormone receptor status: Estrogen receptor- and/or progesterone receptor-positive tumor Patients with stable brain metastases (i.e., no neurological symptoms and no corticosteroid treatment) are eligible PATIENT CHARACTERISTICS: Male or female Menopausal status not specified ECOG performance status 0-2 Life expectancy ≥ 12 weeks Neutrophil count > 1,500/mm³ Platelet count > 100,000/mm³ AST and/or ALT < 3 times upper limit of normal (ULN) Creatinine < 1.5 times ULN Bilirubin < 1.5 times ULN Clinically normal cardiac function (i.e., LVEF normal by MUGA or ECHO) No current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic live disease) No ischemic heart disease within the past 6 months Normal 12-lead ECG No active or uncontrolled infections No serious illnesses or medical conditions, including any of the following: Hypercalcemia Malabsorption syndrome Chronic alcohol abuse Hepatitis HIV Cirrhosis Able to swallow and retain oral medication No psychological, familial, sociological, or geographical condition potentially hampering study compliance Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after completion of study treatment PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 2 days since prior and no concurrent inducers or inhibitors of CYP3A4, including any of the following: Rifabutin Clarithromycin Cyclosporine Voriconazole Fluoxetine Paroxetine Midazolam Isoniazid Dihydralazine Digitoxin Coumadin Phenytoin Verapamil Diltiazem Herbal constituents (e.g., bergamottin and glabridin) At least 2 weeks since prior aromatase inhibitor Aromatase inhibitors in the adjuvant and/or metastatic setting allowed At least 1 year since prior tamoxifen citrate No other concurrent anticancer therapy or investigational agents

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pierre Fumoleau, MD, PhD

Organizational Affiliation

Centre Georges Francois Leclerc

Official's Role

Study Chair

Facility Information:

Facility Name

Centre Regional Rene Gauducheau

City

Dijon

ZIP/Postal Code

21079

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

25065668

Citation

Fumoleau P, Koch KM, Brain E, Lokiec F, Rezai K, Awada A, Hayward L, Werutsky G, Bogaerts J, Marreaud S, Cardoso F. A phase I pharmacokinetics study of lapatinib and tamoxifen in metastatic breast cancer (EORTC 10053 Lapatam study). Breast. 2014 Oct;23(5):663-9. doi: 10.1016/j.breast.2014.07.003. Epub 2014 Jul 24.

Results Reference

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Lapatinib and Tamoxifen in Treating Patients With Advanced or Metastatic Breast Cancer

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