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Sponsors and Collaborators: |
Sarah Cannon Research Institute SCRI Oncology Research Consortium Novartis |
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Information provided by: | Sarah Cannon Research Institute |
ClinicalTrials.gov Identifier: | NCT00632489 |
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.
Condition | Intervention | Phase |
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Breast Cancer |
Drug: LBH589 Drug: Capecitabine Drug: Lapatinib |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Open Label, Active Control, Single Group Assignment, Safety Study |
Official Title: | A Phase I Study of LBH589 in Combination With Capecitabine ± Lapatinib |
Estimated Enrollment: | 55 |
Study Start Date: | May 2008 |
Estimated Study Completion Date: | May 2010 |
Estimated Primary Completion Date: | May 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
MTD of LBH589 with Capecitabine
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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.
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2: Experimental
LBH589 and Lapatinib
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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: Lapatinib
Lapatinib, 1000 mg PO daily will be added to this combination.
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3: Experimental
LBH589, Capecitabine and Lapatinib (Breast Cancer Patients)
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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.
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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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Laboratory values as follows:
Additional Breast Cancer Patient Subset (Part 2 and Part 3) Inclusion Criteria:
Patient may have received these drugs in combination or in sequence for the treatment of locally advanced or metastatic disease and/or adjuvant therapy.
Exclusion Criteria:
Impaired cardiac function including any of the following:
Additional Breast Cancer Patient Subset (Part 2 and Part 3) Exclusion Criteria:
1. Prior treatment with lapatinib
Contact: Howard A. Burris, III, M.D. | (615) 329-7274 | howard.burris@scresearch.net |
Contact: Trials Info | (615) 329-7274 | trialsinfo@scresearch.net |
United States, Tennessee | |
Tennessee Oncology, PLLC | Recruiting |
Nashville, Tennessee, United States, 37023 |
Study Chair: | Howard A Burris, III, M.D. | SCRI Oncology Research Consortium |
Responsible Party: | SCRI Oncology Research Consortium ( Howard A. Burris, III, M.D. ) |
Study ID Numbers: | SCRI REFMAL 119 |
Study First Received: | March 3, 2008 |
Last Updated: | April 21, 2009 |
ClinicalTrials.gov Identifier: | NCT00632489 History of Changes |
Health Authority: | United States: Food and Drug Administration |
Refractory Malignancy Breast Cancer LBH589 Capecitabine Lapatinib |
Antimetabolites Capecitabine Skin Diseases Breast Neoplasms |
Lapatinib Protein Kinase Inhibitors Breast Diseases |
Antimetabolites Capecitabine Antimetabolites, Antineoplastic Skin Diseases Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Breast Neoplasms Enzyme Inhibitors |
Lapatinib Protein Kinase Inhibitors Pharmacologic Actions Neoplasms Neoplasms by Site Therapeutic Uses Breast Diseases |