PhII Neo-Adjuvant Letrozole & Lapatinib in Pts w/HER2+ & Hormone Receptor+ Operable Breast CA SPORE

NCT00499681 | Terminated Phase 2 Results DMC

• 4 other identifiers: VICC BRE 0660VU-VICC-BRE-0660VU-VICC-061102GSK-LAP107087
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 4

Brief Summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving letrozole together with lapatinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This randomized phase II trial is studying how well giving letrozole together with lapatinib works in treating postmenopausal women with stage I, stage II, or stage III breast cancer that can be removed by surgery.

Conditions

Breast Cancer

Keywords

stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Pathological Complete Response

  Progressive disease (PD): \>=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): \>=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.

  at 14 weeks

Study Arms (2)

Arm I

EXPERIMENTAL

Patients receive Lapatinib and Letrozole once daily for two weeks, following tumor measurement patients receive Lapatinib and Letrozole once daily for 14 weeks.

Drug: lapatinib ditosylate; Drug: letrozole

Arm II

EXPERIMENTAL

Patients receive Letrozole and placebo once daily for 2 weeks, following tumor measurement patients receive Letrozole and Lapatinib once daily for 14 weeks.

Drug: lapatinib ditosylate; Drug: letrozole; Other: placebo

Interventions

lapatinib ditosylate DRUG

Given once daily, 1500mg, for 2 weeks; Given once daily, 1500mg, for 14 weeks in Arm II

Also known as: GW572016

Arm I; Arm II

letrozole DRUG

Given once daily, 2.5mg, for 2 weeks; Given once daily, 2.5mg, for 14 weeks

Also known as: Femara

Arm I; Arm II

placebo OTHER

Given once daily for 2 weeks

Arm II

Eligibility Criteria

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

You may qualify if:

• Clinical stage I, II, or III operable invasive mammary carcinoma, confirmed by histological analysis
• Measurable residual tumor at the primary site
• Measurable disease is defined as any mass that can be reproducibly measured by physical examination, mammogram, and/or ultrasound and can be accurately measured in at least one dimension (longest diameter to be recorded) as 10 mm (1 cm)
• Available core biopsies from the time of diagnosis
• May include sections of paraffin-embedded material
• Scheduled to undergo surgical treatment with either segmental resection or total mastectomy
• Prior history of contralateral breast cancer allowed if patient has no evidence of recurrence of their initial primary breast cancer within the last 5 years
• HER2-positive by Herceptest (3+) or FISH
• ER-positive and/or PR-positive by IHC

You may not qualify if:

• Locally recurrent breast cancer
• Evidence of distant metastatic disease (i.e., lung, liver, bone, or brain metastases)
• PATIENT CHARACTERISTICS:
• Female
• Postmenopausal, as defined by any of the following:
• At least 55 years of age
• Under 55 years of age and amenorrheic for at least 12 months OR follicle-stimulating hormone (FSH) values ≥ 40 IU/L and estradiol levels ≤ 20 IU/L
• Prior bilateral oophorectomy or prior radiation castration with amenorrhea for at least 6 months
• ECOG performance status 0-1
• ANC ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• AST and ALT ≤ 1.5 times ULN
• Able to swallow and retain oral medication

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Vanderbilt-Ingram Cancer Center - Cool Springs

Nashville, Tennessee, 37064, United States

Location

Vanderbilt-Ingram Cancer Center at Franklin

Nashville, Tennessee, 37064, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

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

Limitations and Caveats

Due to the restrictive nature of the eligibility criteria, only a total of 6 out of the planned 36 patients were accrued in 2 years, leading to early termination of the study. Hence, both clinical and correlative data were deemed uninterpretable.

Results Point of Contact

• Title: Ingrid Mayer, MD, Principal Investigator
• Organization: Vanderbilt-Ingram Cancer Center

ingrid.mayer@vanderbilt.edu

615-936-2033

Study Officials

• Ingrid Mayer, MD

  Vanderbilt-Ingram Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine; Clinical Director, Breast Cancer Program; Medical Oncologist

Study Record Dates

• First Submitted: July 10, 2007
• First Posted: July 11, 2007
• Study Start: July 1, 2007
• Primary Completion: October 1, 2009
• Study Completion: December 1, 2010
• Last Updated: August 10, 2012
• Results First Posted: July 10, 2012

Record last verified: 2012-08

Locations

US (4)