Non-Small-Cell Lung CarcinomaPhase 1/2HCH003NCT01090830
Safety and Efficacy of Belinostat When Used With Standard of Care Chemotherapy for Untreated Non-small Cell Lung Cancer
A Phase 1/2 study testing Belinostat, carboplatin, paclitaxel and bevacizumab in people with Non-Small-Cell Lung Carcinoma, run by Holy Cross Hospital, Florida at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small-Cell Lung Carcinoma
- What is being tested?
- Belinostat, carboplatin, paclitaxel and bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2010to Feb 2012
- 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
- 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).
Who cannot join
- 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.
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- 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.
- Known hypersensitivity to either platinum compounds or paclitaxel, or any components of the study medications, and inability for desensitization.
- Peripheral neuropathy NCI ≥ Grade 2.
- Co-existing active severe infection or any co-existing medical condition likely to interfere with trial procedures.
- Known infection with HIV, or known active Hepatitis B or C infection.
- Pregnant or lactating.
- not willing to use effective contraception during the study and until 6 months post-completion of last cycle administered
Trial locations and contacts
1 site in 1 country.
United States1 site
Holy Cross Hospital, Inc
Fort Lauderdale, Florida, 33308
About this study
Official title: Phase Ib/II Study to Determine the Recommended Dose, Safety, and Preliminary Efficacy of Belinostat When Used in Combination With Carboplatin, Paclitaxel, and Bevacizumab in Patients With Untreated Non-small Cell Lung Cancer.
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.
Read the detailed description
This is a Phase Ib/II, single center, open label, dose-finding study to evaluate the use of Belinostat when given with standard of care chemotherapy in patients with untreated, non-small cell lung cancer (NSCLC). In the Phase Ib portion, dose limiting toxicity evaluation will be used to determine the maximum tolerated dose (MTD) of Belinostat when given with fixed doses of bevacizumab, carboplatin, and paclitaxel(a BelCap-B regimen). Three dose levels of Belinostat are proposed (600mg/kg, 800mg/kg, 1000mg/kg). Determination of MTD will be the basis for establishing set dosing for the phase II component of the study.
The phase II portion of the study includes further drug safety evaluation and a preliminary assessment of efficacy of Belinostat when used with specified induction and maintenance regimens. Response will be evaluated through the RECIST criteria. Additional analysis will be done to estimate the time to response, progression free survival, median survival, and overall survival (OS) in study participants to 2 years post-initiation of cycle 1.
Based on a standard 3 x 3 statistical design, the phase Ib portion may accrue between 3 to 12 participants. Phase II will have a minimum sample size of 10 and a maximum of 16 patients. Participants who complete the Phase I portion and are able to advance to Phase II, will be evaluable for the Phase II objectives.
- Conditions
- Non-Small-Cell Lung Carcinoma
- Being tested
- Belinostat, carboplatin, paclitaxel and bevacizumab
- 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
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Belinostat, carboplatin, paclitaxel and bevacizumabDrug
Also called Belionostat, PDX101, Bevacizumab, Carboplatin
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.
| Study group | Role | What they receive |
|---|---|---|
| Belinostat | Experimental | This is a one arm, open label study of the investigational medication Belinostat. Receives: Drug: Belinostat, carboplatin, paclitaxel and bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (4)
To evaluate overall survival with this investigational treatment.
The percentage of participants who are alive at 2 years post initiation of investigational treatment.
Measured: 2 years
Long-term safety (late-effects up to 2 years)
Long-term (up to 2 years) safety evaluation of the investigational treatment will be evaluated by ongoing evaluation of adverse events/late-effects using the NCI Common Toxicity Criteria.
Measured: 2 years
Evaluate disease response of participants who receive this investigational medication regimen
Response to therapy will be measured by the RECIST criteria. The investigators will assess the percentage of research participants whose disease status indicates a response to investigational treatment according to the RECIST criteria.
Measured: 2 years
To evaluate progression-free survival
The number (%) of participants who do not show evidence of disease progression (according to RECIST criteria)at 2 years post initial administration of the investigational product.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2010 (estimated)
- Study startApr 2010
- Primary completionFeb 2012
- Study completionFeb 2012
Why it stopped: Principal Investigator has left institution. IND withdrawn.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small-Cell Lung CarcinomaStudies 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Holy Cross Hospital, Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paul Papagni, Holy Cross Hospital, Florida
- Investigators
- Martin E Guiterrez, MD, Principal investigator, Holy Cross Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01090830
- Sponsor's protocol ID
- HCH003
- Acronym
- HCH003
- Status last verified
- Mar 2013
- First submitted
- 22 Mar 2010
- Last updated
- 23 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib/II Study to Determine the Recommended Dose, Safety, and Preliminary Efficacy of Belinostat When Used in Combination With Carboplatin, Paclitaxel, and Bevacizumab in Patients With Untreated Non-small Cell Lung Cancer.
- ClinicalTrials.gov ID
- NCT01090830
- Acronym / sponsor ID
- HCH003 / HCH003
- Conditions
- Non-Small-Cell Lung Carcinoma
- Keywords
- Non small cell lung cancer, Belinostat, carboplatin, Paclitaxel, Bevacizumab, chemotherapy, Maximum Tolerated Dose, Neoplasms, Pulmonary
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Principal Investigator has left institution. IND withdrawn.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Holy Cross Hospital, FloridaUniversity, hospital or other
- Study start
- Apr 2010
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 23 Mar 2010 (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.
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.
Detailed description
This is a Phase Ib/II, single center, open label, dose-finding study to evaluate the use of Belinostat when given with standard of care chemotherapy in patients with untreated, non-small cell lung cancer (NSCLC). In the Phase Ib portion, dose limiting toxicity evaluation will be used to determine the maximum tolerated dose (MTD) of Belinostat when given with fixed doses of bevacizumab, carboplatin, and paclitaxel(a BelCap-B regimen). Three dose levels of Belinostat are proposed (600mg/kg, 800mg/kg, 1000mg/kg). Determination of MTD will be the basis for establishing set dosing for the phase II component of the study.
The phase II portion of the study includes further drug safety evaluation and a preliminary assessment of efficacy of Belinostat when used with specified induction and maintenance regimens. Response will be evaluated through the RECIST criteria. Additional analysis will be done to estimate the time to response, progression free survival, median survival, and overall survival (OS) in study participants to 2 years post-initiation of cycle 1.
Based on a standard 3 x 3 statistical design, the phase Ib portion may accrue between 3 to 12 participants. Phase II will have a minimum sample size of 10 and a maximum of 16 patients. Participants who complete the Phase I portion and are able to advance to Phase II, will be evaluable for the Phase II objectives.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Belinostat | Experimental | Drug: Belinostat, carboplatin, paclitaxel and bevacizumabThis is a one arm, open label study of the investigational medication Belinostat. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (21 listed)
- 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.
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, paclitaxel and bevacizumabAlso: Belionostat, PDX101, Bevacizumab, CarboplatinInduction 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. | Drug | Belinostat |
Primary outcome
The recommended phase II dose of Belinostat when used in combination with carboplatin, paclitaxel and bevacizumab.
Time frame: 1 year
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.
4 secondary outcomes
To evaluate overall survival with this investigational treatment.
Time frame: 2 years
Long-term safety (late-effects up to 2 years)
Time frame: 2 years
Evaluate disease response of participants who receive this investigational medication regimen
Time frame: 2 years
To evaluate progression-free survival
Time frame: 2 years
Results and safety
The study was stopped early (reason given: Principal Investigator has left institution. IND withdrawn.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2018.
- Holy Cross HospitalLink provided by the sponsor.
- Michael and Diane Bienes Comprehensive Cancer CenterLink provided by the sponsor.
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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.
Martin E Guiterrez, MD principal investigator
Holy Cross Hospital
1 site 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 and bevacizumab in people with Non-Small-Cell Lung Carcinoma, run by Holy Cross Hospital, Florida at 1 site 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 6 inclusion and 21 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: stopped early, as of the sponsor's last update on 23 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 was stopped early (reason given: Principal Investigator has left institution. IND withdrawn.). Results are not available in the source record.
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?
The recommended phase II dose of Belinostat when used in combination with carboplatin, paclitaxel and bevacizumab. (time frame: 1 year). 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 23 Feb 2018.