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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.

Phase 1/Phase 2
18 Years
Not Enrolling
Non-Small-Cell Lung Carcinoma

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Trial Information

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.

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

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.

Inclusion Criteria:

- 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).

Exclusion Criteria:

- 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.

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Outcome Measure:

The recommended phase II dose of Belinostat when used in combination with carboplatin, paclitaxel and bevacizumab.

Outcome Description:

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.

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Martin E Guiterrez, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Holy Cross Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

April 2010

Completion Date:

February 2012

Related Keywords:

  • Non-Small-Cell Lung Carcinoma
  • 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
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Holy Cross Hospital, Inc Fort Lauderdale, Florida  33308