Study of Imatinib, a Platelet-derived Growth Factor Receptor Inhibitor, and LBH589, a Histone Deacetylase Inhibitor, in the Treatment of Newly Diagnosed and Recurrent Chordoma

NCT01175109 | Unknown Phase 1

• 1 other identifier: 15120
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

This is a multi-center study to assess the safety and to determine the maximum tolerated dose of the combination of imatinib and LBH589 in patients with newly diagnosed and recurrent chordoma. For the recurrent population, those patients that do not require immediate surgical resection will be eligible. Patients will be treated with 4 cycles, followed by surgical resection if possible. If indicated, surgery may take place prior to the completion of 4 cycles.

Conditions

Chordoma

Keywords

Chordoma

Outcome Measures

Primary Outcomes (1)

• Number of dose limiting toxicities

  At time of study drug discontinuation

Secondary Outcomes (2)

• Tumor response

  Week 7

• Tumor response

  Week 12

Study Arms (1)

Escalating doses of imatinib and LBH589

EXPERIMENTAL

Study will incorporate a "3+3" dose escalation design.

Drug: Imatinib + LBH589

Interventions

Imatinib + LBH589 DRUG

Escalating doses of imatinib and LBH589 will be administered.

Escalating doses of imatinib and LBH589

Eligibility Criteria

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

You may qualify if:

• Patients greater than or equal to 18 years of age.
• Histologically documented diagnosis of chordoma
• At least one measurable site of disease (as defined by Response Evaluation Criteria in Solid Tumors, see Appendix 3).
• Performance status 0,1, or 2 (ECOG) (see Section 6)
• Patients must have adequate bone marrow and end organ function, as defined as the following:
• WBC \> 3.0 x 109/L
• ANC \> 1.5 x 109/L,
• Platelets \> 100 x 109/L
• Hemoglobin \> 10 gm/dl
• Total bilirubin \< 1.5 x ULN (Does not apply to patients with isolated hyperbilirubinemia (e.g., Gilbert's disease) grade \<3.
• AST/SGOT and ALT/SGPT \< 2.5 x UNL
• Serum creatinine ≤ 2.5 x ULN or 24 hr creatinine clearance ≥ 50ml/min
• Serum albumin ≤ 3g/dL
• Serum amylase and lipase ≤ 1.5 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN

You may not qualify if:

• Patient has received any other investigational agents within 28 days of first day of study drug dosing for treatment of chordoma, unless the disease is rapidly progressing. Patients who have been previously treated with imatinib or LBH589 are ineligible.
• Patients must not be on enzyme inducing anticonvulsants or valproic acid, a seizure medication with HDAC inhibition activity.
• Patient is \< 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
• Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
• Impaired cardiac function including any one of the following:
• Inability to monitor the QT/QTc interval on ECG
• Long QT syndrome or a known family history of long QT syndrome.
• Clinically significant resting brachycardia (\<50 beats per minute)
• QTc \> 450 msec on baseline ECG (using the QTcF formula). If QTcF \>450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
• Myocardial infarction within 12 months prior to starting study
• Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension)
• History of or presence of clinically significant ventricular or atrial tachyarrhythmias
• Female patients who are pregnant or breast-feeding.
• Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
• Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).

Sponsors & Collaborators

• Deric M Park MD: lead

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Chordoma

Interventions

Imatinib Mesylate; Panobinostat

Condition Hierarchy (Ancestors)

Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Hydroxamic Acids; Hydroxylamines; Amines; Hydroxy Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Deric M Park, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor, Department of Neurological Surgery

Study Record Dates

• First Submitted: July 28, 2010
• First Posted: August 4, 2010
• Study Start: October 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 27, 2012

Record last verified: 2012-12

Locations

US (3)