Safety and Efficacy of Belinostat When Used With Standard of Care Chemotherapy for Untreated Non-small Cell Lung Cancer

NCT01090830 | Terminated Phase 1

• 1 other identifier: HCH003
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to establish the safest dose of the investigational medication Belinostat that can be administered with a standard of care chemotherapy regimen of bevacizumab, carboplatin, and paclitaxel. Further study will examine the short and long-term effect (up to 2 years) of this medication on participant's disease status and overall survival.

Conditions

Non-Small-Cell Lung Carcinoma

Keywords

Non small cell lung cancer; Belinostat; carboplatin; Paclitaxel; Bevacizumab; chemotherapy; Maximum Tolerated Dose; Neoplasms, Pulmonary; Lung Cancer; Event Free Survival; Disease free survival; Progression Free Survival; Histone Deacetylase Inhibitors; Treatment Efficacy

Outcome Measures

Primary Outcomes (1)

• The recommended phase II dose of Belinostat when used in combination with carboplatin, paclitaxel and bevacizumab.

  The aim of the initial phase Ib component is to establish the maximum tolerated dose (MTD) of Belinostat when used with a standard of care carboplatin, paclitaxel and bevacizumab course of therapy ("BelCap-B") regimen. The MTD will be determined through the process of dose-limiting-toxicity evaluation.

  1 year

Secondary Outcomes (4)

• To evaluate overall survival with this investigational treatment.

  2 years

• Long-term safety (late-effects up to 2 years)

  2 years

• Evaluate disease response of participants who receive this investigational medication regimen

  2 years

• To evaluate progression-free survival

  2 years

Study Arms (1)

Belinostat

EXPERIMENTAL

This is a one arm, open label study of the investigational medication Belinostat.

Drug: Belinostat, carboplatin, paclitaxel and bevacizumab

Interventions

Belinostat, carboplatin, paclitaxel and bevacizumab DRUG

Induction therapy will include 6 cycles of 5-days of medication administration followed by a 16 day rest period. Belinostat will be given once a day for 5 days total. Three dose levels will be evaluated (600mg/kg, 800 mg/kg, and 1000 mg/kg). In addition, participants will receive fixed doses of intravenous carboplatin (AUC 6), Paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg) once on day 3 of each cycle. Serial disease status evaluations will be done throughout the study. In the absence of significant toxicity or disease progression, participants may continue with a maintenance regimen of bevacizumab and Belinostat for an additional 6 cycles. The dose of Belinostat received during maintenance will be that tolerated in the initial 6 cycles.

Also known as: Belionostat, PDX101, Bevacizumab, Carboplatin, Paraplatin, Paclitaxel, Taxol

Belinostat

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically documented NSCLC confirmed.
• Has advanced NSCLC (Stage IV), not previously treated with any chemotherapy regiment (prior adjuvant chemotherapy and/or chemotherapy/radiation for Stage III allowed).
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan.
• Life expectancy of \> 3 months
• Must have returned to baseline or grade 1 adverse event from any acute toxicity related to prior therapy
• Adequate immune and multisystem organ function (as evidenced by urine and blood values within specified parameters).

You may not qualify if:

• Brain or meningeal metastases. Note, patients with adequately treated brain metastases, e.g. surgically resected, or adequately controlled by radiotherapy, with no residual neurological symptoms due to metastases and no steroid treatment required, can be enrolled. If clinical suspicion, adequate investigations should be performed to rule out brain metastases or meningeal involvement.
• History of a previous malignancy within 5 years with the exception of non-metastatic non-melanoma skin cancer or cervical carcinoma in situ. Prior systemic therapy for other malignancy must be completed at least 5 years before treatment is allowed.
• Lung carcinoma of squamous cell histology (mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible; sputum cytology alone is not acceptable).
• History of hemoptysis within 3 months prior to enrollment
• Current or recent (within 10 days of enrollment) use of aspirin (\>325 mg/day) or chronic use of other non-steroidal anti-inflammatory medications.
• Prior systemic anti-tumor therapy for Stage IV lung cancer. Note, prior radiotherapy is allowed provided treatment was completed at least 2 weeks before enrollment. Prior surgery is allowed if completed at least 4 weeks before enrollment.
• Treatment with investigational agents within the 2 weeks prior to enrollment.
• Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease.
• Hypertension not controlled by medical therapy.
• Significant cardiovascular disease, myocardial infarction within the past 6 months, unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of medication to control heart rate in patients with atrial fibrillation is allowed, if stable medication for at least last month prior to enrollment, or evidence of acute ischemia on electrocardiogram).
• Marked baseline prolongation of QT/QTc interval that required use of concomitant medication that may cause Torsade de Pointes
• Significant, non-healing wounds, acute or non-healing ulcers, or bone fractures within 3 months of fracture.
• Undergone major surgery within 4 weeks of planned initiation of cycle 1.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of enrollment.
• History of any gastrointestinal bleeding within the 3 months prior to enrollment.

Sponsors & Collaborators

• Holy Cross Hospital, Florida: lead

Study Sites (1)

Holy Cross Hospital, Inc

Fort Lauderdale, Florida, 33308, United States

Location

Related Links

• Holy Cross Hospital

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

belinostat; Carboplatin; Paclitaxel; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Martin E Guiterrez, MD

  Holy Cross Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive Director of Clinical Research

Study Record Dates

• First Submitted: March 22, 2010
• First Posted: March 23, 2010
• Study Start: April 1, 2010
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: February 23, 2018

Record last verified: 2013-03

Locations

US (1)