E6508: A Phase II Study of L-BLP25 and Bevacizumab in Unresectable Stage IIIA and IIIB Non-Squamous Non-Small Cell Lung Cancer after Definitive Chemoradiation

Summary

This is a phase II study of L-BLP25 and Bevacizuman after difinitive chemoradiation.
The study consists of:

Concomitant Chemoradiation
-Paclitaxel: once per week for 6 weeks
-Carboplatin: Infused once per week for 6 weeks (immediately following paclitaxel)
-Definitive Radiation: 5 days a week (Mon-Fri) for 6.5 weeks

Patients will be elavuated. Consolidation chemotherapy will be administered for 2 cycles. Patient must start Consolidation Chemotherapy within 4 weeks of completing Concomitant Chemoradiation or the patient[Right Quote]s protocol treatment will be discontinued.


Step 1 – Consolidation Chemotherapy (Cycles 1 and amp; 2)
1 Cycle = 21 days.

Consolidation Chemotherapy:
- Paclitaxel 225 mg/m2 IV over 3 hours on day 1.
- Carboplatin AUC 6 IV 15-30 minute infusion on day 1, immediately following paclitaxel.

All patients with CR, PR, or SD at evaluation at end of Consolidation Chemotherapy may be
registered to Step 2 (Maintenance Therapy). Patients with progressive disease or whose
response is unevaluable will discontinue protocol treatment.

Step 2 – Maintenance Therapy (Cycles 1, 2, 3,…for up to 34 cycles) 1 Cycle = 21 days.

Maintenance therapy will continue for a maximum of 34 cycles or until PD or unacceptable toxicity. Patients must be registered to Maintenance Therapy (Step 2) within 7 days of completing Consolidation Chemotherapy (Step 1).

Patients on Step 2 Will Receive the Following:
- Cyclophosphamide 300 mg/m2 (600 mg maximum) IV over 15 -30minutes – 3 days prior to day 1 of Cycle 1 only.
- Bevacizumab 15 mg/kg IV on day 1 of each cycle.
(A urine dipstick should be performed at baseline then prior to every other course of bevacizumab. Treatment may proceed if dipstick result is 0 –1+. If the result of urine protein dipstick is and amp;gt; 1+, 24 hour urine for protein must be
obtained)
- L-BLP25 Vaccine 806 ug subcutaneously:
-Days 1, 8, and amp; 15 of cycles 1 and amp; 2 then
- Day 1 of cycles 4, 6, 8, … (every other cycle)

Participant Eligibility

1. Patients must have newly diagnosed histologically confirmed non-squamous nonsmall
cell lung cancer (adeno, large cell undifferentiated, bronchoalveolar, and nonsmall
cell carcinoma NOS).
2. Patients must be without significant pleural effusion and have either unresectable
Stage IIIA disease or Stage IIIB disease (TNM staging system AJCC V7).
- “Unresectable” Stage IIIA = Stage IIIA patients with mediastinal lymph node enlargement of > 1 cm but < 2.0 cm on CT scans must have these nodes biopsied (pathologic confirmation) to rule out resectability. These staging procedures are not mandatory for patients with obvious nodal involvement (obvious nodal involvement ≥ 2cm). Patients with stage IIIA must not have
significant pleural effusion.
- All patients with stage IIIB disease (without significant pleural effusion) will be eligible. This includes patients with metastases to contralateral mediastinal or supraclavicular nodes.
- To be eligible patients with either unresectable Stage IIIA disease or Stage IIIB disease must not have significant pleural effusion. Patients without significant pleural effusion will constitute those in whom:
1) pleural effusion is seen on CT scan only (not seen on CXR) or
2) pleural effusion does not reaccumulate after one thoracentesis and is cytologically negative.
o If pleural effusion is seen on CT scan, a CXR must be done.
- If pleural effusion is seen on CT scan only, and not seen on CXR, patient is eligible.
- If pleural effusion is seen on CT scan, and seen on CXR, thorocentesis must be done.
• If fluid does not reaccumulate within 1 week after thoracentesis, cytology must be done:
- If cytologically negative, patient is eligible.
- If cytologically positive, patient is not eligible.
• If fluid does reaccumulate within 1 week after thorocentesis,
patient is not eligible.
• Does patient have either unresectable Stage IIIA disease or Stage IIIB disease
o If Stage IIIA with mediastinal lymph node enlargement between 1 and 2.0 cm, have nodes been biopsied to rule out resectability?
• Is patient without significant pleural effusion?
o If pleural effusion was seen on CT scan, was pleural effusion seen on CXR?
- If pleural effusion was seen on CT scan and CXR after thorocentesis was done, did fluid reaccumulate within 1 week?
o If, after thorocentesis was done and fluid did not reaccumulate
within 1 week, was cytologic result negative?
3. Patients must have measurable or non-measurable disease, as defined by RECIST
(see Section 6). Baseline measurements/evaluations of all sites of disease must be
obtained within 4 weeks prior to registration.
4. Patients must not have CNS metastases. A head CT or MRI is required within 4
weeks prior to registration for evaluation.
5. Patients must have ECOG performance status of 0-1.
6. Patients must have no other active malignancies.
7. Patients must be > 18 years of age.
8. Required bone marrow function laboratory values (obtained within 4 weeks prior to
registration):
- WBC > 4000/mm3 or ANC > 2000/mm3
- Platelets > 140,000/mm3
- Hemoglobin > 9.0 g/dL
9. Required liver function laboratory values (obtained within 4 weeks prior to
registration):
- Total bilirubin < 1.5 mg/dL
- SGOT (AST) < 2.5 times the Institutional upper limit of normal.