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A Phase II Randomized Trial of Paclitaxel, Carboplatin, Bevacizumab With or Without IMC-A12 in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

Phase 2
18 Years
Open (Enrolling)
Adenocarcinoma of the Lung, Bronchoalveolar Cell Lung Cancer, Large Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

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Trial Information

A Phase II Randomized Trial of Paclitaxel, Carboplatin, Bevacizumab With or Without IMC-A12 in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer


I. To evaluate the progression-free survival with the combination of carboplatin,
paclitaxel, and bevacizumab with vs without cixutumumab in patients with stage IV or
recurrent non-squamous, non-small cell lung cancer.


I. To evaluate overall survival and response rate of the above combination in patients with
non-squamous, advanced non-small cell lung cancer.

II. To evaluate the toxicities of the above combination in patients with non-squamous
advanced non-small cell lung cancer.

OUTLINE: Patients are stratified according to ECOG performance status (0 vs 1). Patients are
randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours, carboplatin IV over 30
minutes, and bevacizumab IV over 30-90 minutes on day 1.

ARM II: Patients receive paclitaxel, carboplatin, and bevacizumab as in arm I. Patients also
receive cixutumumab IV over 1 hour on days 1, 8, and 15.In both arms, treatment repeats
every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Treatment with bevacizumab and cixutumumab may continue in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.

Inclusion Criteria:

- Histologically or cytologically confirmed non-squamous, non-small celllung cancer
(NSCLC), including any of the following subtypes*:

- Adenocarcinoma

- Large cell

- Bronchioloalveolar

- NSCLC not otherwise specified

- Advanced disease, as defined by any of the following:

- Stage IV (M1a or M1b)* disease based on the TNM staging system

- Recurrent disease after prior radiotherapy or surgery

- Measurable disease, as defined by RECIST (PET and the PET portion of PET/CT are not
acceptable methods of evaluation for response)

- No prior radiotherapy to the only area of measurable disease unless there is
progression of disease documented by physical examination, imaging tests, or
pathology in this region

- Brain metastases are allowed, provided they have been treated with surgery and/or
radiotherapy, the patient is neurologically stable, and repeat brain imaging shows no
tumor progression in the brain

- Patients must undergo head CT scan or MRI within 4 weeks prior to randomization
for evaluation

- At least 6 weeks since prior craniotomy and ≥ 4 weeks since prior radiotherapy

- ECOG performance status 0-1

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Total bilirubin normal

- Serum creatinine ≤ 1.5 times upper limit of normal (ULN)

- Fasting blood glucose normal (fasting < 120 mg/dL or below ULN)

- AST and ALT ≤ 3 times ULN

- Alkaline phosphatase ≤ 3 times ULN

- Urine protein by dipstick ≤ 1+ (within 2 weeks of randomization) OR urine
protein:creatinine < 1.0

- INR < 1.5 or PTT normal

- Neuropathy ≤ CTCAE grade 1

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment

- No prior allergic reaction to compounds of chemical or biological composition similar
to those of cixutumumab

- No known hypersensitivity to any component of bevacizumab

- No poorly controlled diabetes mellitus

- History of diabetes mellitus allowed, provided blood glucose is within normal

- No history of other invasive malignancies unless there is no active disease and all
treatment has been completed > 3 years prior to study

- Patients with history of in-situ malignancies and curatively resected
nonmelanomatous skin cancer are allowed

- Patients with a history of breast cancer (without evidence of disease for ≥ 3
years) who recently completed adjuvant hormonal therapy < 3 years from the date
of registration are eligible

- No history of thrombotic or hemorrhagic disorders

- No history of bleeding diathesis or coagulopathy

- No bleeding ≥ grade 2 (CTCAE version 3) requiring intervention within the past 4weeks

- No history of gross hemoptysis (defined as > ½ teaspoon of bright red blood)

- No history of hypertensive crisis or hypertensive encephalopathy

- History of hypertension allowed provided it is well-controlled (< 150/90 mm Hg) by
stable anti-hypertensive therapy

- None of the following conditions within the past 6 months:

- Abdominal fistula

- Gastrointestinal perforation

- Intra-abdominal abscess

- Myocardial infarction

- Stroke

- Any CNS cerebrovascular ischemia

- New York Heart Association class II-IV congestive heart failure or severe heart

- Unstable or symptomatic angina pectoris

- Significant vascular disease

- Symptomatic peripheral vascular disease

- No ongoing, serious cardiac arrhythmia requiring medication

- No ongoing, active infection or fever

- No co-existing medical condition, psychiatric illness or limitations that would
interfere with compliance of study requirements

- No serious non-healing wound, ulcer, bone fracture within the past 4 weeks

- No other concurrent anticancer therapy (e.g., biologic agents, chemotherapy, or

- No prior chemotherapy or biologic or molecular targeted therapy for advanced NSCLC

- No prior cixutumumab or another IGF-IR inhibitor

- At least 3 weeks since prior radiotherapy and recovered

- More than 1 year since prior chemotherapy and/or biological or molecular targeted
therapy as part of initial potentially curative therapy (i.e., one regimen of
induction and/or adjuvant and/or concurrent chemoradiotherapy)

- More than 4 weeks since prior and no concurrent major surgical procedure

- More than 7 days since prior minor surgical procedure

- More than 1 week since prior and no concurrent daily treatment with acetylsalicylic
acid (> 325 mg/day) or other non-steroidalanti-inflammatory agents

- More than 1 week since prior and no concurrent dipyridamole (Persantine), ticlopidine
(Ticlid),clopidogrel (Plavix), and/or cilostazol (Pletal)

- No concurrent therapeutic anticoagulation, except prophylactic anticoagulation of
venous access device

- No concurrent combination antiretroviral therapy in HIV-positive patients

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival assessed by Response Evaluation Criteria for Solid Tumors (RECIST)

Outcome Time Frame:

From randomization to disease progression or death from any cause, up to 5 years

Safety Issue:


Principal Investigator

Athanassios Argiris

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

March 2010

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Lung
  • Bronchoalveolar Cell Lung Cancer
  • Large Cell Lung Cancer
  • Recurrent Non-Small Cell Lung Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Adenocarcinoma, Bronchiolo-Alveolar
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



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