Stage IV Non-small Cell Lung CancerPhase 1/2NCT01310244
MTD Study PXD-101 in Combination With Paclitaxel + Carboplatin in Chemotherapy-Naive Patients With Stage IV NSCLC
A Phase 1/2 study testing Belinostat, Carboplatin, Paclitaxel in people with Stage IV Non-small Cell Lung Cancer, run by Acrotech Biopharma Inc. at 4 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IV Non-small Cell Lung Cancer
- What is being tested?
- Belinostat, Carboplatin, Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 4 sitesUnited States
- Study dates
- Dec 2010to Aug 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University Cancer Insitute
Boynton Beach, Florida, 33426
Clearview Cancer Institute (CCI)
Huntsville, Alabama, 35805
Sarcoma Oncology Center
Santa Monica, California, 90403
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
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)
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).
Read the 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
- Being tested
- Belinostat, Carboplatin, Paclitaxel
- 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
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Belinostat, Carboplatin, PaclitaxelDrug
Also called PXD-101
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.
| Study group | Role | What they receive |
|---|---|---|
| Single arm, open label | Experimental | 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. Receives: Drug: Belinostat, Carboplatin, Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 Months
Secondary outcomes (4)
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.
Measured: 24 Months
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.
Measured: 24 Months
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.
Measured: 24 Months
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%].
Measured: 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2011 (estimated)
- Study startDec 2010
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage IV Non-small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acrotech Biopharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Valerio Therapeutics
- Responsible party
- Sponsor
- Investigators
- Brian Matthews, MD, Principal investigator, Clearview Cancer InstituteSant Chawla, MD, Principal investigator, Sarcoma Oncology CenterSaiama Waqar, MD, Principal investigator, Washington University School of MedicineThomas Neiderman, MD, Principal investigator, University Cancer Insitute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01310244
- Sponsor's protocol ID
- SPI-1014-Bel
- Status last verified
- Jan 2020
- First submitted
- 28 Feb 2011
- Last updated
- 6 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01310244
- Acronym / sponsor ID
- SPI-1014-Bel
- Conditions
- 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
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Acrotech Biopharma Inc.Industry (pharma, biotech, devices)
- Collaborators
- Valerio Therapeutics
- Study start
- Dec 2010
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 8 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm, open label | Experimental | Drug: Belinostat, Carboplatin, PaclitaxelAt 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Belinostat, Carboplatin, PaclitaxelAlso: PXD-101Up 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. | Drug | Single arm, open label |
Primary outcome
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.
Time frame: 24 Months
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.
4 secondary outcomes
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.
Time frame: 24 Months
Efficacy when IV belinostat is administered in combination with carboplatin and paclitaxel in patients with chemotherapy naïve Stage IV M1a or M1b NSCLC
Time frame: 24 Months
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
Time frame: 24 Months
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.
Time frame: 24 Months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian Matthews, MD principal investigator
Clearview Cancer Institute
Sant Chawla, MD principal investigator
Sarcoma Oncology Center
Saiama Waqar, MD principal investigator
Washington University School of Medicine
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Belinostat, Carboplatin, Paclitaxel in people with Stage IV Non-small Cell Lung Cancer, run by Acrotech Biopharma Inc. at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 24 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2020.