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)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
TopoTarget A/S
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01310244
First received: February 28, 2011
Last updated: November 1, 2013
Last verified: November 2013
  Purpose

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).


Condition Intervention Phase
Stage IV Non-small Cell Lung Cancer
Drug: Belinostat, Carboplatin, Paclitaxel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Maximum Tolerated Dose and to Evaluate Safety and Efficacy of Belinostat (PXD-101) in Combination With Paclitaxel Plus Carboplatin in Chemotherapy-Naive Patients With Stage IV Non-Small-Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by Spectrum Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: 24 Months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety [ Time Frame: 24 Months ] [ Designated as safety issue: Yes ]
    Safety will be mainly characterized by the number and severity of treatment emergent adverse events, and treatment related AEs that occur or worsen after the first dose of study treatment.

  • Efficacy [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    Efficacy will be evaluated by measuring time to progression from first dose (PFS), and calculating the proportion of patients who achieve either CR or PR (ORR) using RECIST criteria.

  • Tolerability [ Time Frame: 24 Months ] [ Designated as safety issue: Yes ]
    Tolerability will be mainly characterized by the number and severity of treatment emergent adverse events, and treatment related AEs that occur or worsen after the first dose of study treatment.


Estimated Enrollment: 35
Study Start Date: December 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm, open label Drug: 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.
Other Name: PXD-101

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01310244

Locations
United States, Alabama
Clearview Cancer Institute (CCI)
Huntsville, Alabama, United States, 35805
United States, California
Sarcoma Oncology Center
Santa Monica, California, United States, 90403
United States, Florida
University Cancer Insitute
Boynton Beach, Florida, United States, 33426
Lakeland Regional Cancer Center
Lakeland, Florida, United States, 33805
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
TopoTarget A/S
Investigators
Principal Investigator: Brian Matthews, MD Clearview Cancer Institute
Principal Investigator: Sant Chawla, MD Sarcoma Oncology Center
Principal Investigator: Saiama Waqar, MD Washington University School of Medicine
Principal Investigator: Thomas Neiderman, MD University Cancer Insitute
  More Information

Additional Information:
No publications provided

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01310244     History of Changes
Other Study ID Numbers: SPI-1014-Bel
Study First Received: February 28, 2011
Last Updated: November 1, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Spectrum Pharmaceuticals, Inc:
Phase 1/2
MTD
stage IV
NSCLC
chemo-naive
Mixed-cell dose escalation
lung cancer
non-small-cell
phase I
Belinostat
Carboplatin
Paclitaxel
adenocarcinoma
PXD-101

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 15, 2014