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A Phase II Study of Prophylactic Radiation Therapy for the Prevention of Hemoptysis in Advanced Non Small Cell Lung Cancer in Combination With Bevacizumab, Paclitaxel, and Carboplatin in Patients at High Risk for Bevacizumab-Associated Hemoptysis

Phase 2
18 Years
Not Enrolling
Adenosquamous Cell Lung Cancer, Drug/Agent Toxicity by Tissue/Organ, Hemoptysis, Squamous Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

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Trial Information

A Phase II Study of Prophylactic Radiation Therapy for the Prevention of Hemoptysis in Advanced Non Small Cell Lung Cancer in Combination With Bevacizumab, Paclitaxel, and Carboplatin in Patients at High Risk for Bevacizumab-Associated Hemoptysis


I. Evaluate the safety of prophylactic chest radiotherapy, bevacizumab, paclitaxel, and
carboplatin in patients with unresectable stage IIIB or IV non-small cell lung cancer at
high risk for bevacizumab-associated hemoptysis.


I. Assess progression-free survival of patients treated with this regimen. II. Assess the
rate of objective response, overall survival, time to response, and response duration in
irradiated lesions and non-irradiated lesions in these patients.

OUTLINE: This is an open-label, pilot, multicenter study. Patients are assigned sequentially
to 1 of 2 treatment strata.

Stratum I: Patients undergo prophylactic radiotherapy on days 1-5 and 8-12. Patients receive
paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 15. Patients also
receive paclitaxel IV over 3 hours or carboplatin IV over 30-60 minutes and bevacizumab IV
over 30-90 minutes on day 36 (course 2).

Stratum II: Patients undergo prophylactic radiotherapy and receive paclitaxel and
carboplatin as in stratum I. Patients also receive bevacizumab IV over 30-90 minutes on day
15 (course 1). In both strata, treatment with paclitaxel, carboplatin, and bevacizumab
repeats every 21 days for 5-6 courses in the absence of disease progression or unacceptable
toxicity. Patients with complete or partial response or stable disease may continue to
receive single-agent bevacizumab every 21 days in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 12 months.

PROJECTED ACCRUAL: A total of 72 patients will be accrued for this study.

Inclusion Criteria:

- Histologically or cytologically confirmed primary non-small cell lung cancer (NSCLC)*
meeting the following criteria:

- Squamous cell or mixed squamous-nonsquamous histology with predominant squamous
component (≥ 50% squamous) with a primary, unresected endobronchial lesion

- No small cell component

- Centrally located primary tumor, defined by the following:

- Primary tumor of any T stage within or touching the zone of the proximal
bronchial tree

- Zone is defined as a 3-dimensional volume with a perimeter of 2 cm in
each direction around the proximal bronchial tree (carina, right and
left main bronchi, right and left upper lobe bronchi, intermedius
bronchus, right middle lobe bronchus, lingular bronchus, right and
left lower lobe bronchi)

- Any disease within this volume must not invade blood vessels
determined by a contrast-enhanced CT scan evaluation of the entire
thorax with thin slices (≤ 5 mm) through the area of central tumor
bulk (i.e., no evidence of vessel invasion radiological evaluation)

- Stage IIIB (with malignant pleural effusion) or stage IV disease

- Patients with stage IIIB NSCLC without an effusion are eligible if they are not
candidates for combined modality therapy with curative intent (i.e., radical

- At high risk for bevacizumab-associated hemoptysis

- Hemoptysis estimated as between 2.5 mL and 10 mL (largest volume of single
episode of hemoptysis) in the past 2 months

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques or ≥ 10 mm by spiral CT scan

- No known brain metastases by contrast-enhanced CT scan or gadolinium-enhanced MRI of
the brain

- No clinical or radiologic evidence of an existing or impending spinal cord

- ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%

- Life expectancy > 6 months

- WBC ≥ 3,000/mm³

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Bilirubin normal

- AST and ALT ≤ 2.5 times upper limit of normal (ULN)

- Creatinine normal OR creatinine clearance ≥ 50 mL/min

- INR < 1.5

- aPTT ≤ 1.5 times ULN

- No serious medical conditions, including any of the following:

- Unstable angina

- Myocardial infarction or stroke (cerebrovascular accident or transient ischemic
attack) within the past 6 months

- Congestive heart failure

- Active cardiomyopathy

- Unstable ventricular arrhythmia

- Symptomatic peripheral vascular disease

- Active peptic ulcer disease

- Uncontrolled psychotic disorders

- Serious infections

- Other medical conditions potentially aggravated by treatment

- No social situation that would preclude study compliance

- No other active malignancy

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 6 months after
completion of study treatment

- No history of bleeding diathesis or coagulopathy associated with elevated risk of

- No uncontrolled hypertension (i.e., resting blood pressure consistently higher than
systolic > 150 mm Hg and/or diastolic > 100 mm Hg with or without antihypertensive
medication), history of labile hypertension, or history of poor compliance with
antihypertensive medication

- No clinically significant proteinuria (24-hour urine protein < 1,000 mg)

- No serious or nonhealing wound, ulcer, or bone fracture

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 28 days

- No significant traumatic injury within the past 28 days

- No history of known allergy or reaction attributed to compounds of similar chemical
or biological composition to bevacizumab, such as Chinese hamster ovary cell proteins
or other recombinant human or humanized antibodies, Cremophor EL®, or other agents
used in study treatment

- No pre-existing peripheral neuropathy > grade 1

- No prior thoracic radiotherapy

- At least 12 months since prior chemotherapy

- No prior chemotherapy for advanced disease

- No prior therapy with angiogenesis, vascular endothelial growth factor (VEGF), or
VEGF-receptor inhibitors

- Cyclooxygenase-2 inhibitors as a noncancer therapy allowed

- At least 28 days since prior and no concurrent major surgery or open biopsy

- At least 12 months since prior anticancer therapy for any other malignancy except
basal cell carcinoma of the skin, localized prostate cancer, or in situ carcinoma of
the cervix

- At least 10 days since prior therapeutic anticoagulants or therapeutic thrombolytic

- No concurrent aspirin (> 325 mg/day) or antiplatelet agents, including dipyridamole,
ticlopidine, clopidogrel bisulfate, or cilostazol

- Other concurrent nonsteroidal anti-inflammatory drugs allowed

- No other concurrent investigational agents

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent anticancer agents or therapies

- Steroids for pain, anorexia, or quality of life allowed

Type of Study:


Study Design:

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

Outcome Measure:

Safety of treatment as measured by the incidence of grade 3-5 hemoptysis, as assessed by NCI CTCAE version 3.0

Outcome Description:

All toxicities will be tabulated.

Outcome Time Frame:

Up to 12 months after completion of treatment

Safety Issue:


Principal Investigator

Zelanna Goldberg

Investigator Role:

Principal Investigator

Investigator Affiliation:

California Cancer Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

October 2006

Completion Date:

Related Keywords:

  • Adenosquamous Cell Lung Cancer
  • Drug/Agent Toxicity by Tissue/Organ
  • Hemoptysis
  • Squamous Cell Lung Cancer
  • Stage IIIB Non-Small Cell Lung Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Hemoptysis
  • Lung Neoplasms



California Cancer ConsortiumDuarte, California  90033