Trial Information

Phase II Trial OF Oxaliplatin and Gemcitabine With Bevacizumab in Advanced Non-Small Cell Lung Cancer

STUDY OBJECTIVES:

Primary:

To determine the overall time to progression of the combination regimen of Gemcitabine,
Oxaliplatin and Bevacizumab as first-line treatment in patients with Stage IIIB and IV
non-small cell lung cancer.

Secondary

- To determine the overall response rate

- To determine the overall survival.

- To determine the toxicity of Gemcitabine, Oxaliplatin given in combination with
Bevacizumab

ELIGIBILITY CRITERIA

1. Patients must have histologically or cytologically confirmed non-small cell lung cancer
EXCEPT squamous cell carcinoma. Mixed tumors will be categorized by the predominant
cell type unless small cell elements are present in which case the patient is
ineligible. Cytologic or histologic elements can be established on metastatic tumor
aspirates or biopsy.

2. Patients must have advanced NSCLC (Stage IIIB with malignant pleural effusion or Stage
IV or recurrent disease).

3. Patients must have measurable disease (as defined in Section 13.0).

4. ECOG performance status 0 or 1.

5. Patients must not have known CNS metastases. Brain imaging is required within 4 weeks
prior to study entry.

6. No prior systemic treatment for advanced NSCLC is permitted. Prior treatment for
early-stage disease (adjuvant) or for locally-advanced Stage III disease is allowed if
completed at least 12 months prior to registration.

7. Required laboratory values (obtained 2 weeks prior to registration):

7.1 ANC > 1500/mm³. 7.2 Platelets > 100,000/mm³. 7.3 Total Bilirubin < 1.5 mg/dl. 7.4
Transaminases < 5 x ULN.

8. Patients must have adequate renal function as determined by the following tests within
2 weeks prior to registration.

8.1 Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN), AND
Urinalysis < 1+ protein*

* Patients discovered to have >1+ proteinuria at baseline must undergo a 24-hour urine
collection. This must be an adequate collection and must demonstrate <1g of protein/24
hr to allow participation in the study.

9. Patients must be 18 years or older.

10. Pregnant and lactating women are excluded from the study because the agents used in
this study may be teratogenic to a fetus and there is no information on the excretion
of the agents or their metabolites into breast milk. A negative urine or serum
pregnancy test required for women of childbearing potential.

11. Women of childbearing potential and sexually active males must agree to use an accepted
and effective method of contraception (hormonal or barrier methods, abstinence) prior
to study entry and for the duration of the study.

12. Patients treated with radiation therapy must have adverse events from therapy resolved
to grade 2 or less following completion of treatment.

13. Patients must not have ongoing or active infection, symptomatic congestive heart
failure, cerebrovascular accident within 12 months, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

14. Patients must have no deep vein thrombosis or pulmonary embolus within one year of
registration and no ongoing need for full-dose oral or parenteral anticoagulation. Low
dose coumadin (1mg) for maintenance of catheter patency or daily prophylactic aspirin
is allowed.

15. Patients with history of hypertension must be well-controlled (defined as a blood
pressure of >160 mmHg systolic and/or > 110 mmHg diastolic) on a stable regimen of
anti-hypertensive therapy.

16. Patients must not have serious non-healing wound ulcer, or bone fracture, or major
surgical procedure within 3 weeks prior to starting treatment.

17. Patients with a history of gross hemoptysis (defined as bright red blood of a ½
teaspoon or more) will be excluded from this trial

18. No prior malignancy is allowed except for adequately treated basal cell or squamous
cell skin cancer, in situ cervical cancer, or other cancer for which the patient has
been disease-free for five years

TREATMENT PLAN Gemcitabine 1000mg/m2 IV over 30 minutes, on days 1 and 8 followed by
Oxaliplatin 130mg/m2 IV over 2 hours on day 1 followed by Bevacizumab 15 mg/kg IV over 90*
minutes, on day 1 Cycles q 3 weeks x 4 cycles One cycle equals 3 weeks. Patients will be
re-evaluated every 2 cycles. If CR, PR or SD, patients will continue treatment up to four
cycles or until progression or unacceptable toxicity.

Patients achieving CR, PR, or SD after 4 cycles will continue Bevacizumab maintenance:

Bevacizumab 15 mg/kg IV q 3 weeks until relapse/progression