MTD Study PXD-101 in Combination With Paclitaxel + Carboplatin in Chemotherapy-Naive Patients With Stage IV NSCLC

NCT ID: NCT01310244

Last Updated: 2020-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2015-08-31

Brief Summary

To define Phase 1/2 Maximum Tolerated Dose Study of Belinostat (PXD-101) in Combination with Paclitaxel plus Carboplatin in Chemotherapy-Naive Patients with Stage IV Non-Small-Cell Lung Cancer (NSCLC).

Detailed Description

This is a Phase 1/2, multi-center, open label single arm study. Patients meeting all inclusion and exclusion criteria will receive up to 6 cycles of combination therapy of belinostat plus carboplatin (AUC 6) and paclitaxel 200 mg/m2.

During phase I the Maximum Tolerated Dose (MTD) of belinostat in combination with carboplatin and paclitaxel will be determined in patients with Stage IV non-small cell lung cancer who have received no prior systemic chemotherapy. The dose escalation study will be conducted using traditional escalation rule of 3+3 design, during the first cycle of therapy. Belinostat will be assessed at a starting dose level of 1000 mg/m2 and multiple dose levels may be evaluated. Doses of belinostat, carboplatin and paclitaxel will remain constant throughout the study, unless dose modification is required by toxicity. Treatment is given on days 1-5 of every 21-day cycle. Routine safety evaluations will be conducted on days, 1, 8, and 15 of every cycle. Tumor measurement will be done after every 2 cycles of the treatment.

Additional 20 patients will be treated at the MTD defined dose during phase II expansion portion of the study.

All patients will receive up to 6 cycles of combination therapy and be followed until occurrence of unacceptable toxicity, disease progression, withdrawal of consent or death.

Conditions

Stage IV Non-small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single arm, open label

At the study entry each patient will receive a dose level assignment which will include a specific dose level and the dose of IV belinostat in mg/m2 to be administered during the study treatment.

Belinostat will be infused over 30 minutes once daily on Days 1-5 of each 21-day cycle. On Day 3, the infusion of belinostat must be completed at least 1 hour prior to the start of the paclitaxel infusion. Dose of belinostat will be assigned at study entry. The same dose and level will remain throughout the entire study for each patient and no dose adjustment will be allowed, except due to toxicity.

Group Type: EXPERIMENTAL

Belinostat, Carboplatin, Paclitaxel

Intervention Type: DRUG

Up to 6 cycles of combination therapy of belinostat plus carboplatin (AUC 6) and paclitaxel 200 mg/m2. Initial dose of belinostat will be 1000mg/m2 for MTD dose escalation evaluation.

Interventions

Belinostat, Carboplatin, Paclitaxel

Up to 6 cycles of combination therapy of belinostat plus carboplatin (AUC 6) and paclitaxel 200 mg/m2. Initial dose of belinostat will be 1000mg/m2 for MTD dose escalation evaluation.

Intervention Type: DRUG

Other Intervention Names

PXD-101

Eligibility Criteria

Inclusion Criteria

• A histologically or cytologically confirmed diagnosis of Stage IV (M1a or M1b) NSCLC. Patients with mixed non-small cell histologies are eligible
• No prior chemotherapy for the treatment of advanced NSCLC
• Prior adjuvant therapy for early stage lung cancer is allowed if completed ≥ 12 months prior to enrollment
• Age >= 18 years
• Adequate organ function
• Any treatment with investigational agent must have completed ≥ 4 weeks prior to enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Negative pregnancy test for women of childbearing potential.
• Patients with brain metastases allowed if:

• Directed local therapy was completed 2 weeks prior to enrollment;
• There is no evidence of disease progression and;
• Steroids are not required

Exclusion Criteria

• Patients with mixed tumors of small cell features
• Known infection with HIV, hepatitis B or hepatitis C
• Baseline prolongation of QT/QTcF interval or required concomitant medication that may cause Torsade de Pointes
• Preexisting ≥Grade 2 neuropathy
• Valproic acid treatment within 2 weeks of study enrollment
• Systemic steroids, for any indication, stabilized at >10 mg/day prednisone
• Known allergy or hypersensitivity to any component of belinostat, paclitaxel or carboplatin
• Co-existing active infection or any other uncontrolled medical condition likely to interfere with trial procedures
• Active concurrent malignancy (except basal cell carcinoma or cervical intraepithelial neoplasia, other potentially cured malignancy that has been in remission for five years or prior adjuvant therapy for early stage lung cancer that is completed ≥ 12 months ago)
• Pregnant or breast-feeding women

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Valerio Therapeutics

INDUSTRY

Sponsor Role: collaborator

Acrotech Biopharma Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brian Matthews, MD

Role: PRINCIPAL_INVESTIGATOR

Clearview Cancer Institute

Sant Chawla, MD

Role: PRINCIPAL_INVESTIGATOR

Sarcoma Oncology Center

Saiama Waqar, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Thomas Neiderman, MD

Role: PRINCIPAL_INVESTIGATOR

University Cancer Insitute

Locations

Clearview Cancer Institute (CCI)

Huntsville, Alabama, United States

Sarcoma Oncology Center

Santa Monica, California, United States

University Cancer Insitute

Boynton Beach, Florida, United States

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Other Identifiers

SPI-1014-Bel

Identifier Type: -

Identifier Source: org_study_id