LBH589, Paclitaxel, Carboplatin +/- Bevacizumab for Solid Tumors

NCT ID: NCT00556088

Last Updated: 2010-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-12-31

Study Completion Date

2010-07-31

Brief Summary

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This phase I protocol will evaluate the safety and tolerability of the combination of LBH589 and paclitaxel/carboplatin. The combination of LBH589, paclitaxel/carboplatin, and bevacizumab will also be evaluated for tolerability and preliminary antitumor activity in a subset of patients with advanced non-small cell lung cancer.

Detailed Description

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Conditions

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Solid Tumors

Keywords

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LBH589 Phase I Solid Tumors Paclitaxel Carboplatin Bevacizumab Dose escalation

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1

Part I Phase I dose escalation trial. LBH589 will be administered orally on Monday and Thursday or Tuesday and Friday each week (twice weekly). Paclitaxel and carboplatin will be administered intravenously every 21 days.

Part II LBH589, paclitaxel, and carboplatin dosing will be determined in the first phase of this study (Phase I). The drug dosages to be administered will be reduced one level from the determined Maximum Tolerated Dose (MTD). In addition, bevacizumab 15 mg/kg will be added to the second portion of this trial.

Group Type EXPERIMENTAL

LBH589, Paclitaxel, Carboplatin, Bevacizumab

Intervention Type DRUG

LBH589 will be administered orally twice weekly. Paclitaxel and carboplatin will be administered intravenously every 21 days.

Once the MTD is established, drug dosages will be adjusted downward by one dose level and bevacizumab 15mg/kg intravenously every 3 weeks will be administered to a subset of patients with non-small cell lung cancer.

Interventions

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LBH589, Paclitaxel, Carboplatin, Bevacizumab

LBH589 will be administered orally twice weekly. Paclitaxel and carboplatin will be administered intravenously every 21 days.

Once the MTD is established, drug dosages will be adjusted downward by one dose level and bevacizumab 15mg/kg intravenously every 3 weeks will be administered to a subset of patients with non-small cell lung cancer.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Histologically documented metastatic or locally advanced, incurable malignancy for which paclitaxel and carboplatin is clinically appropriate for example, non-small cell lung, breast, ovarian, head and neck cancer, and carcinoma of unknown primary.
2. Male or female patients aged \>= 18 years old.
3. Maximum of 3 prior regimens in a metastatic setting allowed and may include other targeted agents, immunotherapy and chemotherapy.
4. Measurable disease by RECIST criteria.
5. ECOG PS 0 or 1.
6. Laboratory values as follows:

ANC \>= 1500/μL Hgb \>= 9 g/dL Platelets \>= 100,000/uL Bilirubin \<= upper limit normal (ULN) AST/SGOT and ALT/SGPT \<= 2.5 x ULN or \<= 5.0 x ULN in patients with liver metastases Creatinine \<= 2.0 mg/dL Or 24-hour Creatinine Clearance \>= 50 ml/min Albumin \>= 3 g/dL Potassium \>= lower limit normal (LLN) Phosphorous \>= LLN Calcium \>= LLN Magnesium \>= LLN PT/INR and PTT \<= 1.5 x ULN
7. Peripheral neuropathy \< grade 1.
8. Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment.
9. Life expectancy \> 12 weeks.
10. Accessible for treatment and follow-up.
11. All patients must be able to understand the nature of the study and give written informed consent prior to study entry.

Exclusion Criteria

1. Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
2. 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 minutes. Patients wit 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 \[See Appendix B\]).
* Right bundle branch block and left anterior hemiblock (bifasicular block).
* Atrial fibrillation or flutter.
3. Uncontrolled hypertension (systolic blood pressure \[BP\] 160 or diastolic BP \>95mm Hg) or uncontrolled cardiac arrhythmias.
4. Active CNS disease, including meningeal metastases.
5. Known diagnosis of human immunodeficiency virus (HIV) infection.
6. Unresolved diarrhea \> CTCAE grade 1.
7. Chemotherapy, investigational drug therapy, major surgery \< 4 weeks prior to starting study drug or patients that have not recovered from side effects of previous therapy.
8. Patient is \< 5 years free of another primary malignancy except if the other primary malignancy is not currently clinically significant or 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.
9. Concomitant use of any anti-cancer therapy or radiation therapy.
10. Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double barrier method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days of the first administration of oral LBH589.
11. Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment. One of these methods must be a condom.
12. Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis).
13. Other concurrent severe, uncontrolled infection or intercurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
14. Patients with uncontrolled coagulopathy.
15. Abnormal thyroid function (TSH or free T4) detected at screening.Patients with known hypothyroidism who are stable on thyroid replacement are eligible.


1. Patients with tumor types other than advanced non-small cell lung cancer and patients with squamous cell histology non-small cell lung cancer.
2. Patients who have had a major surgical procedure (not including mediastinoscopy), open biopsy, or significant traumatic injury within 6--8 weeks of beginning bevacizumab. Fine needle aspiration, core biopsy, mediastinoscopy or other minor surgical procedure within 7 days of beginning bevacizumab.
3. Patients receiving full-dose oral or parenteral anticoagulation. Patients receiving thrombolytic therapy within 10 days of starting bevacizumab are also ineligible. Patients may receive anticoagulation therapy, (1 mg coumadin daily) for port clot prophylaxis.
4. Patients with serious non-healing wound, ulcer, or bone fracture.
5. Patients with evidence of bleeding diathesis or coagulopathy.
6. Patients with history of hemoptysis (defined as bright red blood of ½ teaspoon or more per episode) within 3 months prior to study enrollment.
7. History of myocardial infarction or unstable angina within 6 months of first bevacizumab dose.
8. Patients with proteinuria at screening for as demonstrated by either:

a. Urine protein creatinine (UPC) ration \>1.0 at screening OR b. Urine dipstick for proteinuria \> 2+ (patients discovered to have \> 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate \< 1 g of protein in 24 hours to be eligible.
9. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to beginning bevacizumab.
10. History of stroke or transient ischemic attack within 6 months prior to first bevacizumab dose.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis

INDUSTRY

Sponsor Role collaborator

SCRI Development Innovations, LLC

OTHER

Sponsor Role lead

Responsible Party

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Sarah Cannon Research Institute

Principal Investigators

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Howard A. Burris, M.D.

Role: STUDY_CHAIR

SCRI Development Innovations, LLC

Locations

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Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Site Status

Countries

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United States

Other Identifiers

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SCRI REFMAL 121

Identifier Type: -

Identifier Source: org_study_id