NCT00632489

LBH589 in Combination With Capecitabine Plus/Minus (±) Lapatinib in Breast Cancer Patients

A Phase I Study of LBH589 in Combination With Capecitabine ± Lapatinib

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: SCRI Development Innovations, LLC · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This single center Phase I dose escalation trial will evaluate the safety, tolerability and efficacy of LBH589 when combined with capecitabine and lapatinib in three parts. Part 1 will determine the maximum tolerated doses (MTD) of LBH589 when combined with capecitabine. Parts 2 and 3 will be limited to locally recurrent or metastatic breast cancer patients, ICH 3+ overexpression or FISH amplification documented locally. Part 2 will evaluate the safety of the MTD of LBH589 determined in Part 1 when paired with lapatinib 1000 mg by mouth (PO) daily. Parts 2 and 3 will be limited to locally recurrent or metastatic breast cancer patients, ICH 3+ overexpression or FISH amplification documented locally. Part 3 will evaluate the tolerability and effectiveness of the triplet combination, LBH589, capecitabine and lapatinib in breast cancer patients.

Detailed description

LBH589 will be evaluated when administered twice weekly at the following possible dose levels: 20 mg, 30 mg, 45 mg, and 60 mg. Capecitabine will be paired with LBH589 and will range in dose from 825 mg/m2 to 1250 mg/m2 orally BID 14 of every 21 days. Treatment cycles will be 21 days in length. Once determined safe, 10 additional patients will be treated at the determined MTD to further assess safety. The second portion of this study will assess QTc prolongation with the LBH589 and lapatinib combination. A subset of 6 patients will be treated with the LBH589 one dose below the MTD determined during Part I. If tolerated, 6 additional patients will receive LBH589 at the MTD established in Part I with lapatinib (capecitabine will not be administered in this subset of patients). If there are no clinically significant findings in the LBH589 and lapatinib subset, the study will advance to a third portion which combines the three drugs LBH589, capecitabine, and lapatinib. The triple combination will initially administer lapatinib 1000 mg orally daily with LBH589 and capecitabine at one dose level below the established MTD. If tolerated, LBH589 and capecitabine doses will be escalated to the MTD. Toxicity assessments will be ongoing and disease assessments will be repeated every 2 treatment cycles. If all dose level combinations are explored, a total of 45-55 patients will be required to accommodate for the additional patients enrolled in the QTc subset and to establish the recommended phase II dose of the combination regimen.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	LBH589	LBH589 will be evaluated when administered twice weekly at the following possible dose levels: 20 mg, 30 mg, 45 mg, and 60 mg. Capecitabine will be paired with LBH589 and will range in dose from 825 mg/m2 to 1250 mg/m2 orally BID 14 of every 21 days. Treatment cycles will be 21 days in length. Once determined safe, 10 additional patients will be treated at the determined MTD to further assess safety.
DRUG	Capecitabine	Capecitabine will be administered orally twice daily for 14 days out of every 21 days.
DRUG	Lapatinib	Lapatinib, 1000 mg PO daily will be added to this combination.

Timeline

• Start date: 2008-05-01
• Primary completion: 2009-01-01
• Completion: 2011-07-01
• First posted: 2008-03-10
• Last updated: 2015-06-08
• Results posted: 2015-06-08

Locations

1 site across 1 country: United States