Back to resultsMTD Study PXD-101 in Combination With Paclitaxel + Carboplatin in Chemotherapy-Naive Patients With Stage IV NSCLC
Primary Purpose
Stage IV Non-small Cell Lung Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Belinostat, Carboplatin, Paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Stage IV Non-small Cell Lung Cancer focused on measuring 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
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
Sites / Locations
- Clearview Cancer Institute (CCI)
- Sarcoma Oncology Center
- University Cancer Insitute
- Washington University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single arm, open label
Arm Description
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.
Outcomes
Primary Outcome Measures
To determine the Maximum Tolerated Dose ( MTD) of belinostat in combination with carboplatin and paclitaxel in patient with Stage IV non-small cell lung cancer who has received no prior systemic chemotherapy.
At study entry each eligible patient will be assigned a specific dose level and dose of IV belinostat in mg/m2, to be administered daily on Days 1 to 5 each 21 day cycle, for up to 6 cycles. Dose escalation within each patient is not allowed during this study. At each dose level cohort of up to 6 patients may be evaluated during Cycle 1 of therapy. Multiple dose levels may be evaluated to determine the Maximum Tolerated Dose (MTD) of IV belinostat, in combination with 6 cycles of IV carboplatin and paclitaxel, for chemo-naïve patients with Stage IV NSCLC.
Secondary Outcome Measures
Safety and Tolerability when IV belinostat is administered in combination with carboplatin and paclitaxel in patients with chemotherapy naïve Stage IV M1a or M1b NSCLC.
Safety will be based on treatment emergent adverse events (TEAEs), including DLTs will be graded by CTCAE version 4.02, and grouped by the MedDRA preferred term, and summarized by worst grade severity per patient. TEAEs are those adverse events that occur or worsen on or after first study treatment up through 30 days post last study treatment, and/or any treatment-related. 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. Deaths, non-fatal serious adverse events (SAEs), and other AEs leading to discontinuation of study treatment will be summarized.
Efficacy when IV belinostat is administered in combination with carboplatin and paclitaxel in patients with chemotherapy naïve Stage IV M1a or M1b NSCLC
Efficacy variable of this study is best overall response, using RECIST criteria - complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), and not evaluable (NE) - as determined by the investigator.The efficacy endpoint is objective response rate (ORR), defined as the proportion of patients with target lesions who achieve either a CR or a PR.
Progression-free survival (PFS) when IV belinostat is administered in combination with carboplatin and paclitaxel in patients with chemotherapy naïve Stage IV M1a or M1b NSCLC
progression-free survival (PFS) will be analyzed, defined as the duration of time from date of first study treatment to date of first documented progression or death from any cause. All treated patients will be included in the analysis of PFS. Patients without a documented progression or death will be censored at the last disease assessment.
Objective response rate (ORR) when IV belinostat is administered in combination with carboplatin and paclitaxel in patients with chemotherapy naïve Stage IV M1a or M1b NSCLC.
The efficacy endpoint is objective response rate (ORR), defined as the proportion of patients with target lesions who achieve either a CR or a PR. A two-sided exact 95% confidence.
interval (CI) will be calculated for ORR. For example, if 24 patients are to be treated, including 20 patients with target lesions at baseline, and 8 patient achieve a CR or a PR, then the response rate will be 40% with a 95% CI of [19%, 64%].
Full Information
NCT ID
NCT01310244
First Posted
February 28, 2011
Last Updated
January 2, 2020
Sponsor
Acrotech Biopharma Inc.
Collaborators
Onxeo
1. Study Identification
Unique Protocol Identification Number
NCT01310244
Brief Title
MTD Study PXD-101 in Combination With Paclitaxel + Carboplatin in Chemotherapy-Naive Patients With Stage IV NSCLC
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)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Acrotech Biopharma Inc.
Collaborators
Onxeo
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage IV Non-small Cell Lung Cancer
Keywords
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single arm, open label
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Belinostat, Carboplatin, Paclitaxel
Other Intervention Name(s)
PXD-101
Intervention Description
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.
Primary Outcome Measure Information:
Title
To determine the Maximum Tolerated Dose ( MTD) of belinostat in combination with carboplatin and paclitaxel in patient with Stage IV non-small cell lung cancer who has received no prior systemic chemotherapy.
Description
At study entry each eligible patient will be assigned a specific dose level and dose of IV belinostat in mg/m2, to be administered daily on Days 1 to 5 each 21 day cycle, for up to 6 cycles. Dose escalation within each patient is not allowed during this study. At each dose level cohort of up to 6 patients may be evaluated during Cycle 1 of therapy. Multiple dose levels may be evaluated to determine the Maximum Tolerated Dose (MTD) of IV belinostat, in combination with 6 cycles of IV carboplatin and paclitaxel, for chemo-naïve patients with Stage IV NSCLC.
Time Frame
24 Months
Secondary Outcome Measure Information:
Title
Safety and Tolerability when IV belinostat is administered in combination with carboplatin and paclitaxel in patients with chemotherapy naïve Stage IV M1a or M1b NSCLC.
Description
Safety will be based on treatment emergent adverse events (TEAEs), including DLTs will be graded by CTCAE version 4.02, and grouped by the MedDRA preferred term, and summarized by worst grade severity per patient. TEAEs are those adverse events that occur or worsen on or after first study treatment up through 30 days post last study treatment, and/or any treatment-related. 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. Deaths, non-fatal serious adverse events (SAEs), and other AEs leading to discontinuation of study treatment will be summarized.
Time Frame
24 Months
Title
Efficacy when IV belinostat is administered in combination with carboplatin and paclitaxel in patients with chemotherapy naïve Stage IV M1a or M1b NSCLC
Description
Efficacy variable of this study is best overall response, using RECIST criteria - complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), and not evaluable (NE) - as determined by the investigator.The efficacy endpoint is objective response rate (ORR), defined as the proportion of patients with target lesions who achieve either a CR or a PR.
Time Frame
24 Months
Title
Progression-free survival (PFS) when IV belinostat is administered in combination with carboplatin and paclitaxel in patients with chemotherapy naïve Stage IV M1a or M1b NSCLC
Description
progression-free survival (PFS) will be analyzed, defined as the duration of time from date of first study treatment to date of first documented progression or death from any cause. All treated patients will be included in the analysis of PFS. Patients without a documented progression or death will be censored at the last disease assessment.
Time Frame
24 Months
Title
Objective response rate (ORR) when IV belinostat is administered in combination with carboplatin and paclitaxel in patients with chemotherapy naïve Stage IV M1a or M1b NSCLC.
Description
The efficacy endpoint is objective response rate (ORR), defined as the proportion of patients with target lesions who achieve either a CR or a PR. A two-sided exact 95% confidence.
interval (CI) will be calculated for ORR. For example, if 24 patients are to be treated, including 20 patients with target lesions at baseline, and 8 patient achieve a CR or a PR, then the response rate will be 40% with a 95% CI of [19%, 64%].
Time Frame
24 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brian Matthews, MD
Organizational Affiliation
Clearview Cancer Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sant Chawla, MD
Organizational Affiliation
Sarcoma Oncology Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Saiama Waqar, MD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Thomas Neiderman, MD
Organizational Affiliation
University Cancer Insitute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clearview Cancer Institute (CCI)
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35805
Country
United States
Facility Name
Sarcoma Oncology Center
City
Santa Monica
State/Province
California
ZIP/Postal Code
90403
Country
United States
Facility Name
University Cancer Insitute
City
Boynton Beach
State/Province
Florida
ZIP/Postal Code
33426
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
12. IPD Sharing Statement
Learn more about this trial
MTD Study PXD-101 in Combination With Paclitaxel + Carboplatin in Chemotherapy-Naive Patients With Stage IV NSCLC
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