CALGB 30607 - "Randomized, Phase III, Double-Blind Placebo-Controlled Trial of Sunitinib as Maintenance Therapy in Non-Progressing Patients Following an Initial Four Cycles of Platinum-Based Combination Chemotherapy in Advanced, Stage IIIB/IV Non-Small Cell Lung Cancer"

Treatment Plan    (Supplied Drug:  Sunitinib/placebo)

Randomize 3-5 wks after Day 1 of Cycle 4.  Continue protocol tx until disease progression or unacceptable toxicity.

Arm A

Sunitinib:  37.5mg (three 12.5mg caps), PO, QD

Arm B

Placebo (for Sunitinib):  3 caps, PO, QD

Eligibility

• Histol- or cytol-documented primary NSCLC.

• Stg IIIB or IV.  Must not be candidate for combined modality therapy (chemoradiotherapy).

• No brain mets, spinal cord compression, or carcinomatous meningitis.

• No cavitary lesions.

• Must have received 1 chemo regimen for Stg IIIB or IV NSCLC.  Must include 4 cycles of platinum-based doublet chemo w/ or w/o Bevacizumab (Bevacizumab may not be given beyond 4th cycle of chemo).  Must have CR, PR, or stable disease to 1st line chemo and no disease progression.  Must be registered 3-5 wks following Day 1 of Cycle 4 of prior therapy.

• No prior adjuv chemo for Stg I-III resected NSCLC or combined modality therapy for Stg III NSCLC.

• No other primary therapy (including experimental therapy) for NSCLC.  Palliative RT must be completed >1 wk b/f planned start of protocol therapy.

• Must have meas or non-meas disease:

  • Meas disease:  Lesions that can be accurately meas in >1 dimension (longest diameter to be recorded) as >2cm w/conventional techniques or >1cm w/spiral CT.

  • Non-meas disease:  All other lesions, including small lesions (longest diameter <20mm w/conventional techniques or <10mm w/spiral CT) & truly non-meas lesions (i.e., bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonis, abdominal masses that are not confirmed & followed by imaging techniques), & cystic lesions.

• Age >18.

• ECOG perf status 0-1.

• No pregnant or nursing women.

• No ongoing cardiac dysrhythmias, atrial fib, or QTc interval >500msec.  Agents w/proarrhythmic potential are not recommended while on protocol therapy (see protocol list of agents).

• Class I NYHA heart failure is allowed.  Class II NYHA heart failure is allowed if >1 of following is met:

  • Asymptomatic on treatment

  • Prior anthracycline exposure

  • Have received central throracic RT that included heart in radiotherapy port

  No Class III or IV NYHA heart failure w/i 12 mos pre-regist allowed.

• No MI, severe/unstable angina, coronary/peripheral artery bypass graft or stenting, CVA, or TIA w/i last year.

• No HTN that is uncontrolled by meds (>150/100mmHg despite optimal medical therapy). 

• No use of therapeutic anticoagulation for thromboembolic disease.  Low doses of coumadin (<2mg daily) are allowed for prophylaxis of thrombosis.

• No hx of venous thrombosis, PE, or hypercoagulopathy syndrome.

• No hx of pulmonary hemorrhage, bleeding diathesis, or hemoptysis.  Pts w/blood-tinged or streaked sputum are allowed if hemoptysis is <5ml blood/episode & <10ml blood/24-hr period (investigator's best estimate).

• No hx of hypothyroidism if pt is currently euthyroid.

• No abdominal fistula, GI perforation, intra-abdominal abscess, serious or non-healing wound, ulcer, or bone fx w/i 28 days of beginning tx.

• No use of specific CYP3A4 inhibitors or inducers (see protocol for list of agents & time frames).

• Able to take PO meds.

• Granulocytes >1500/mcl; platelets >100,000/mcl; total bili <1.5x ULN; SGOT& SGPT <2.5x ULN (<5x ULN if liver mets); creat <1.5mg/dl .

• PRESTUDY REQUIREMENTS:

  Within 16 days pre-regist:  All bloodwork, H&P, EKG

  Within 28 days pre-regist:  Any xray, scan, or US used for tumor msmt

  Within 42 days pre-regist:  Baseline exams used for screening; any xray, scan, or US of uninvolved organs not used for tumor msmt

  • H&P, progress notes, pulse, BP, wt, perf status

  • Tumor msmts

  • CBC/diff/platelets

  • Lytes, BUN/creat, SGOT, SGPT, bili

  • TSH

  • PT

  • EKG

  • Pregnancy test (if applicable)

  • Eval of cardiac LVEF (prn)

  • CT chest, liver, adrenals

  • Bone scan or PET scan

  • MRI brain

  • Blood submission (for pharmacogenetic study; w/pt's consent)*

  • QOL (w/pt's consent)

  *      Two 10ml purple tops (EDTA) for genotyping & plasma.  Process per protocol & store at 4^oC until shipping.  Ship same day as collected on a cold pack via overnight delivery (Ship Mon-Fri) to CALGB Path Coordinating Office; Columbus, OH.

• Signed informed consent.