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SWOG S0819 - "A Randomized, Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizumab with or without Concurrent Cetuximab in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC)"
NOTE: Requires electronic submission of serial CT or MRI via AG Mednet. KCCOP will submit the images to AG Mednet if they are supplied on CD to KCCOP by the treating facility.
Treatment Plan (Supplied Drug: Cetuximab)
RANDOMIZATION
Arm 1: Chemo w/o Cetuximab +/- Bevacizumab
vs
Arm 2: Chemo w/Cetuximab +/- Bevacizumab
STRATIFICATION
Pts may be place in Bevacizumab-INAPPROPRIATE stratum at their request or at investigator's discretion.
Bevacizumab-Appropriate
vs
Bevacizumab-Inappropriate
Arm 1A: Bevacizumab-APPROPRIATE (q 21 days x 6 cycles)
Paclitaxel: 200mg/m2, IV over 3 hrs
Carboplatin: AUC=6 (modified Calvert formula), IV over 30 mins (immed following Paclitaxel)
Bevacizumab: 15mg/kg, IV over 90 mins +/- 15 mins (1 hr following Carboplatin), continues past 6 cycles until 1 of protocol criteria met
Arm 1B: Bevacizumab-INAPPROPRIATE (q 21 days x 6 cycles)
Paclitaxel: 200mg/m2, IV over 3 hrs
Carboplatin: AUC=6 (modified Calvert formula), IV over 30 mins (immed following Paclitaxel)
Arm 2A: Bevacizumab-APPROPRIATE (q 21 days x 6 cycles)
Cetuximab: 400mg/m2 (loading dose), IV over 2 hrs, Cycle 1 Week 1 only
Cetuximab: 250mg/m2 (maintenance dose), IV over 1 hr, q week starting Week 2 (continues past 6 cycles until 1 of protocol criteria met)
Paclitaxel: 200mg/m2, IV over 3 hrs (1 hr following Cetuximab)
Carboplatin: AUC=6 (modified Calvert formula), IV over 30 mins (immed following Paclitaxel)
Bevacizumab: 15mg/kg, IV over 90 mins +/- 15 mins (1 hr following Carboplatin), continues past 6 cycles until 1 of protocol criteria met
Arm 2B: Bevacizumab-INAPPROPRIATE (q 21 days x 6 cycles)
Cetuximab: 400mg/m2 (loading dose), IV over 2 hrs, Cycle 1 Week 1 only
Cetuximab: 250mg/m2 (maintenance dose), IV over 1 hr, q week starting Week 2 (continues past 6 cycles until 1 of protocol criteria met)
Paclitaxel: 200mg/m2, IV over 3 hrs (1 hr following Cetuximab)
Carboplatin: AUC=6 (modified Calvert formula), IV over 30 mins (immed following Paclitaxel)
Eligibility
Histol- or cytol-proven primary Stg IV NSCLC (adenocarcinoma, large cell carcinoma, squamous, or unspecified). May be new dx or recurrent after prior surgery &/or RT. No additional lesions in ipsilateral non-prim lobe w/o M1a or M1b disease.
CT or MRI brain to evaluate for CNS disease w/i 42 days pre-regist. Must not have brain mets unless: 1) mets have been treated & are controlled >2 wks following tx, AND 2) pt has no residual neuro dysfunction off corticosteroids >1 day.
Meas or non-meas disease by CT or MRI. CT from combined PET/CT may be used to document non-meas disease only unless it meets protocol's diagnostic quality. Assess meas disease w/i 28 days pre-regist (no pleural effusions, ascites, or lab parameters as only evidence of disease). Assess non-meas disease w/i 42 days pre-regist. Central radiology review required.
Must have sufficient tumor tissue available & agree to specimen submission for EGFR FISH testing & other translational medicine studies. Must be offered participation in banking for future research.
No prior chemo for any stage NSC lung cancer. No prior platinum-based chemo for any purpose. No prior Cetuximab, Gefitinib, Erlotinib, or other investigational agents targeting the EGFR pathway. No prior Bevacizumab for any purpose other other VEGF-related agents. No prior chimerized or murine monoclonal antibody therapy for any purpose or have documented presence of HAMA.
Prior RT allowed if recovered from all toxicities at regist. Meas disease must be o/s previous RT field or must have progressed.
Time from surgery or bx is dependent on whether pt will receive Bevacizumab:
Pts who are Bevacizumab-appropriate AND Bevacizumab is planned: >28 days since major surgery or significant traumatic injury. Recovered from all associated toxicities at regist. No anticipated need for major surgery during protocol tx. No core bx, mediastinoscopy, pleurodesis, or VATS pericardial window w/i 14 days pre-regist. Contact Study Coordinator with questions on surgical procedures.
Pts who are Bevacizumab-inappropriate OR Bevacizumab is not planned: >28 days since major surgery or significant traumatic injury. Recovered from all associated toxicities at regist. No anticipated need for major surgery during protocol tx. No core bx, mediastinoscopy, pleurodesis, or VATS pericardial window w/i 7 days pre-regist. Contact Study Coordinator with questions on surgical procedures.
Within 14 days pre-regist: ANC >1500/mcl; platelets >100,000/mcl; Hgb >9g/dL; serum creat <IULN and calc or meas CrCl >50cc/min (Cockroft-Gault formula); UPC ratio* (for UPC ratio >0.5, 24-hr urine protein must be <1000mg); serum bili & SGOT or SGPT both <2x IULN. Notes: If SGOT & SGPT done, both must be <2x IULN. If liver mets, bili & either SGOT or SGPT must be <5x IULN. * Only pts who will be receiving Bevacizumab.
Zubrod 0-1.
No >Grade 2 symptomatic neuropathy-sensory (NCI CTC v3.0).
No documented acute hepatitis or active or uncontrolled infection.
No CVA w/i past 6 mos, MI or unstable angina, uncontrolled HTN, NYHA >Grade 2 CHF, serious cardiac arrhythmia requiring meds, or clinically significant perip vascular disease.
No hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies.
Must provide prior smoking hx.
No other prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, adequately treated Stg I or II cancer currently in CR, or any other cancer disease-free >5 yrs.
No pregnant or nursing women. Men/Women of reproductive potential must use effective contraception (see protocol for details).
PRESTUDY REQUIREMENTS:
H&P, wt, perf status, disease asmt
CBC/diff/platelets
Serum creat
Calc or meas CrCl
UPC ratio (only if Bevacizumab is planned)
Total bili
SGOT or SGPT
Alk phos*
INR
Albumin*
LDH*
Serum Na, Ca, Mg*
Plasma & buffy coat submission (MANDATORY)**
Tissue submission (MANDATORY)***
Image submission#
CT or MRI prn disease asmt (use same method throughout study)
Brain CT/MRI
Bone scan (if clinically indicated)*
EKG*
* Recommended for good medical practice. Results do not determine eligibility.
** 10ml plasma & buffy coat specimens in two 5-10cc purple-top (EDTA) tubes. Process per protocol (preferably w/i 2 hrs after venipuncture) & freeze at -80oC until ready for shipment. Ship on dry ice via overnight delivery (ship Mon-Thur only to: Lab #201; SWOG Specimen Repository - Solid Tissue, Myeloma & Lymphoma Division). Contact KCCOP for kit. Samples not processed immediately after blood draw should be refrigerated at 4oC until processing.
*** 1-2 FFPE tissue blocks containing tumor or needle aspirate slides from time of dx (or subsequent, but prior to therapy). If blocks unavailable, 10-12 unstained slides are acceptable. Tumor material must be reviewed by local pathologist to ensure sufficient tumor cells present in the sample. Cytology can be accepted only if paraffin-embedded as cell blocks. Ship at ambient temp to: Lab #78; UCD Biorepository Core Facility; Aurora, CO.
# Serial CT or MRI must be submitted to QARC for review. KCCOP will submit images to AG Mednet if the images are supplied on CD by the treating facility.
Signed informed consent.