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

NCT00632489 | Completed Phase 1 Results

• 1 other identifier: SCRI REFMAL 119
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Breast Cancer

Keywords

Refractory Malignancy; Breast Cancer; LBH589; Capecitabine; Lapatinib

Outcome Measures

Primary Outcomes (2)

• To Determine the Maximum Tolerated Doses (MTD) and Dose-limiting Toxicities (DLT) of LBH589 in Combination With Capecitabine When Administered to Patients With Refractory and Advanced Tumor Types That Are Sensitive to 5-fluorouracil

  MTD for Capecitabine, BID

  18 months

• To Determine the Maximum Tolerated Doses (MTD) and Dose-limiting Toxicities (DLT) of LBH589 in Combination With Capecitabine When Administered to Patients With Refractory and Advanced Tumor Types That Are Sensitive to 5-fluorouracil

  MTD for Panobinostat, twice weekly

  18 months

Secondary Outcomes (2)

• To Evaluate the Antitumor Activity of LBH589 in Combination With Capecitabine in Patients With Refractory and Advanced Tumors

  18 months

• To Evaluate the Tolerability and Preliminary Efficacy of Established Doses of LBH589 and Capecitabine With Lapatinib in a Limited Number of Patients With HER2+ Breast Cancer

  18 months

Study Arms (3)

LBH589 with Capecitabine

EXPERIMENTAL

MTD, LBH589 with Capecitabine

Drug: LBH589; Drug: Capecitabine

LBH589 and Lapatinib

EXPERIMENTAL

LBH589 and Lapatinib

Drug: LBH589; Drug: Lapatinib

LBH589, Capecitabine and Lapatinib

EXPERIMENTAL

LBH589, Capecitabine and Lapatinib (Breast Cancer Patients)

Drug: LBH589; Drug: Capecitabine; Drug: Lapatinib

Interventions

LBH589 DRUG

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.

Also known as: Panobinostat

LBH589 and Lapatinib; LBH589 with Capecitabine; LBH589, Capecitabine and Lapatinib

Capecitabine DRUG

Capecitabine will be administered orally twice daily for 14 days out of every 21 days.

Also known as: Xeloda

LBH589 with Capecitabine; LBH589, Capecitabine and Lapatinib

Lapatinib DRUG

Lapatinib, 1000 mg PO daily will be added to this combination.

Also known as: Tykerb, Tyverb

LBH589 and Lapatinib; LBH589, Capecitabine and Lapatinib

Eligibility Criteria

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

You may qualify if:

• Histologically documented metastatic or locally unresectable, incurable malignancy for which capecitabine is clinically appropriate.
• Male or female patients aged ≥ 18 years old.
• Maximum of 3 prior regimens in a metastatic setting allowed and may include other targeted agents, immunotherapy and chemotherapy.
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
• Baseline MUGA or ECHO must demonstrate LVEF \> than the lower limits of the institutional normal.
• Laboratory values as follows:
• ANC \> 1500/μL
• Hgb \> 9 g/dL
• Platelets \> 100,000/uL
• Bilirubin \< 1.5 mg/dL
• AST/SGOT \< 2.5 x ULN or \< 5.0 x ULN and ALT/SGPT in patients with liver metastases
• Creatinine \< 1.5 mg/dL or calculated creatinine clearance \> 50 ml/min
• Albumin \> 3 g/dL
• Potassium \> lower limit of normal (LLN)

You may not qualify if:

• Prior treatment with an HDAC inhibitor or current treatment with valproic acid.
• Previous treatment with capecitabine.
• Impaired cardiac function including any of the following:
• Screening ECG with a QTc \> 450 msec.
• Congenital long QT syndrome.
• History of sustained ventricular tachycardia.
• Any history of ventricular fibrillation or torsades de pointes.
• Bradycardia defined as heart rate \< 50 beats per minute. Patients with a pacemaker and heart rate \> 50 beats per minute are eligible.
• Myocardial infarction or unstable angina within 6 months of study entry.
• Congestive heart failure (NY Heart Association class III or IV).
• Right bundle branch block and left anterior hemiblock (bifascicular block).
• Atrial fibrillation or flutter.
• Ongoing therapy with antiarrhythmics or other medications associated with QTc prolongation.
• Uncorrected hypokalemia or hypomagnesaemia.
• Uncontrolled hypertension (systolic blood pressure \[BP\] 180 or diastolic BP \> 100 mm Hg) or uncontrolled cardiac arrhythmias.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Novartis: collaborator

Study Sites (1)

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms

Interventions

Panobinostat; Capecitabine; Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Quinazolines

Results Point of Contact

• Title: John D Hainsworth, MD
• Organization: Sarah Cannon Research Institute

asksarah@scresearch.net

1-877-691-7274

Study Officials

• Howard A Burris, III, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2008
• First Posted: March 10, 2008
• Study Start: May 1, 2008
• Primary Completion: January 1, 2009
• Study Completion: July 1, 2011
• Last Updated: June 8, 2015
• Results First Posted: June 8, 2015

Record last verified: 2015-06

Locations

US (1)