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Phase II Study of Biweekly Carboplatin and Gemcitabine With Bevacizumab as 1st Line Treatment in Patients With Advanced, Inoperable Stage IIIb/IV NSCLC

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

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Trial Information

Phase II Study of Biweekly Carboplatin and Gemcitabine With Bevacizumab as 1st Line Treatment in Patients With Advanced, Inoperable Stage IIIb/IV NSCLC

Treatment with Carboplatin and gemcitabine is one of the most active combination therapies
used for first-line therapy of NSCLC. The optimum schedule for administration of
carboplatin and gemcitabine is currently unknown.

The addition of bevacizumab to another comparable platinum combination showed an overall
survival advantage and a significantly greater response rate and progression-free survival.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed non-small cell lung
cancer (NSCLC) EXCEPT squamous cell carcinoma or predominantly squamous. 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

- Must have disease that is not curative by standard methods.

- Prior adjuvant systemic chemotherapy, immunotherapy, or biological therapy is
allowed, except for prior use of bevacizumab. If gemcitabine was used, more than six
months must have elapsed between completion of adjuvant therapy and disease
progression. Patient must be at least 14 days from previous systemic therapy (at
least 30 days for investigational agents) and have recovered from the acute toxic
effects of the treatment as determined by the treating physician prior to study
registration. Prior therapy other than adjuvant therapy is not allowed.

- Prior radiation therapy must be completed at least 14 days of study registration and
subjects must fully recover from acute toxicities as determined by the treating
physician. Prior radiation to > 25% of bone marrow is not allowed. Prior radiation
therapy to the whole pelvis is not allowed.

- Disease status must be measurable or non-measurable as defined by Response Evaluation
Criteria in Solid Tumors (RECIST) criteria.

- ECOG Performance status of 0 or 1

- Age 18 years or greater

- Adequate organ function within 14 days of study registration including the following:

- Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L,
platelets ≥ 100 x 10^9/L, hemoglobin ≥ 9 g/dL

- Hepatic: bilirubin ≤ 1.5 times the upper limit of normal (× ULN), alkaline
phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤
3.0 × ULN (ALP, AST, and ALT ≤ 5 × ULN is acceptable if liver has tumor

- Renal: Adequate renal function as evidenced by creatinine clearance of >
50ml/min, estimated by the Cockcroft-Gault equation or urine dipstick for
proteinuria < 2+ (patients discovered to have ≥2+ proteinuria on dipstick
urinalysis at baseline should undergo a 24 hour urine collection and must
demonstrate ≤ 1g of protein in 24 hours to be eligible)

- Coagulation: INR < 1.5, PTT < the upper limits of normal (ULN) unless stable on
therapeutic anticoagulation at study entry. The addition of anticoagulants after
study start is not allowed.

- Women of childbearing potential and sexually active males are required to use an
effective method of contraception (i.e., a hormonal contraceptive, intra-uterine
device, diaphragm with spermicidal, condom with spermicidal, or abstinence) during
the study and for 3 months after the last dose of study drug.

- Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

- Intrathoracic 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 acceptable for
inclusion. Subjects with extrathoracic-only squamous cell NSCLC are eligible.
Subjects with only peripheral lung lesions of any NSCLC histology will also be
eligible. A peripheral lesion is defined as a lesion in which the epicenter of the
tumor is < 2 cm from the costal or diaphragmatic pleura in a three-dimensional
orientation based on each lobe of the lung and is > 2 cm from the trachea, main and
lobar bronchi.

- Pregnant (positive pregnancy test within 14 days of study enrollment) or
breast-feeding. Gemcitabine and carboplatin are pregnancy category D - clear evidence
of risk in pregnancy; bevacizumab is pregnancy category C - risk in pregnancy cannot
be ruled out. Pregnancy testing is not required for post-menopausal (defined as
absence of menses for the preceding 24 consecutive months) or surgically sterilized

- Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or
diastolic blood pressure > 100 mmHg on antihypertensive medications)

- Any prior history of hypertensive crisis or hypertensive encephalopathy

- New York Heart Association (NYHA) Grade II or greater congestive heart failure

- History of stroke or transient ischemic attack within 6 months prior to study

- Clinically significant peripheral vascular disease (e.g., aortic aneurysm, aortic

- Symptomatic peripheral vascular disease

- Evidence of bleeding diathesis or coagulopathy in the absence of therapeutic

- Current or recent (within 10 days of enrollment) use of aspirin (>325 mg/day) or
chronic use of other NSAIDs known to inhibit platelet function Treatment with
dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or
cilostazol (Pletal)

- Requiring therapeutic anticoagulation

- Current, ongoing treatment with full-dose warfarin or its equivalent (i.e.,
unfractionated and/or low molecular weight heparin)

- History of thrombotic or hemorrhagic disorders

- T4 tumors with invasion of the heart or great vessels

- Presence or history of central nervous system or brain metastases, except for treated
brain metastases. Treated brain metastases are defined as having no evidence of
progression or hemorrhage after treatment and no ongoing requirement for
dexamethasone, as ascertained by clinical examination and brain imaging (MRI/CT)
during the screening period. Anticonvulsants are allowed, providing the subject is on
a stable dose. Treatment for brain metastases may include whole brain radiotherapy,
radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed
appropriate by the treating physician. Subjects with CNS metastases treated by
radiotherapy within 28 days of Day 1 will be excluded. Subjects treated by
neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will
be excluded.

- History of another malignancy other than NSCLC except in situ carcinoma of the
cervix; adequately treated nonmelanomatous carcinoma of the skin; low grade (Gleason
score ≤ 6) localized prostate cancer or other prior malignancy treated at least 2
years previously with no evidence of recurrence

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to treatment start, anticipation of need for major surgical procedure during
the course of the study

- Minor surgical procedures such as fine needle aspirations or core biopsies within 7
days prior to treatment start

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to treatment start

- Serious, non-healing wound, ulcer, or bone fracture, or the presence of a serious
active infection

- History of hemoptysis defined as bright red blood of 1/2 teaspoon or more in the
previous 1 month before enrollment

- Patients with known hypersensitivity to any of the components of carboplatin,
gemcitabine or bevacizumab.

- Known HIV or Hepatitis B or C (active, previously treated or both)

- Inability to comply with study and/or follow-up procedures

- Life expectancy < 12 weeks.

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:

Time to Progression

Outcome Description:

Time to progression (progression free survival)is defined as the time from the start of treatment until first documented sign of disease progression or death due to any cause. For subjects who do not progress, time to progression will be censored at the time of last tumor assessment.

Outcome Time Frame:

From Enrollment Through 2 Years

Safety Issue:


Principal Investigator

Priya Kumar, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota


United States: Food and Drug Administration

Study ID:




Start Date:

March 2007

Completion Date:

May 2010

Related Keywords:

  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Non-Small-Cell Lung
  • Gemcitabine
  • Carboplatin
  • Bevacizumab
  • Biological therapy
  • Drug therapy
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung



University of Minnesota Cancer CenterMinneapolis, Minnesota  55455
Hubert H. Humphrey Cancer CenterCoon Rapids, Minnesota  55433