NCI Community Oncology Research Program - Protocol Summary
ECOG-ACRIN E4512 - "A Phase III Double-Blind Trial for Surgically Resected Early Stage Non-Small Cell Lung Cancer: Crizotinib Versus Observation for Patients with Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein"
The summary below serves as a brief review of the treatment plan and eligibility for the protocol.
This summary is not intended to be used in place of the full eligibility & treatment information in the protocol.
Please contact NCORP-KC for complete protocol information.
Lung Clinical Trial
CANCER TYPE: Non-Small Cell - Stage II
RESEARCH BASE: CTSU E4512
NCT NUMBER: 02201992
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UPDATED ON 01/08/2019 (20:16:20)
NSC, Stg IB (>4cm), II, or IIIA, non-squamous, completely resected, prior regist to A151216 (ALCHEMIST); Crizotinib vs observation. DCP-001 Eligible
NOTE: ALK mutation status & registration to ALCHEMIST (Alliance A151216) must be done pre-randomiz.
Treatment Plan (Supplied Drug: Crizotinib / placebo)
RANDOMIZATION (Cycle = 21 days)
ARM A - Crizotinib: 250mg, PO, BID (q12hrs), Days 1-21, x 2 yrs
ARM B - Observation
- Age >18.
- Patients must have undergone complete surgical resection of their stage IB (≥ 4 cm), II, or non-squamous IIIA NSCLC per AJCC 7th edition and have had negative margins. N3 disease is not allowed.
- Baseline Chest CT with or without contrast must be performed within 6 months (180 days) prior to randomization to ensure no evidence of disease. If clinically indicated additional imaging studies must be performed to rule out metastatic disease
- ECOG perf status 0-1.
- Must be registered to ALCHEMIST (Alliance A151216) pre-randomiz.
- Positive for translocation or inversion events involving the ALK gene locus (e.g. resulting in EML4-ALK fusion) as determined by the Vysis Break Point FISH assay and defined by an increase in the distance between 5’ and 3’ ALK probes or the loss of the 5’ probe. This must have been performed:
- By a local CLIA certified laboratory: Report must indicate the results as well as the CLIA number of the laboratory which performed the assay. Tissue must be available for submission for central, retrospective confirmation of the ALK fusion status via ALCHEMIST-SCREEN (ALLIANCE A151216). OR
- Patient registered to and the ALK fusion status performed centrally on the ALCHEMIST-SCREEN (ALLIANCE A151216).
- No pregnant or nursing women.
- Negative blood or urine pregnancy test (if applicable - see §3.1.8) w/i 72 hrs pre-randomiz.
- Men/Women of reproductive potential must use effective contraception.
- No uncontrolled intercurrent illness, not limited to: serious ongoing or active infection; symptomatic CHF; unstable angina; uncontrolled cardiac arrhythmia; or psychiatric illness/social situation that limits study compliance.
- No interstitial fibrosis or interstitial lung disease.
- No prior tx w/Crizotinib or other ALK inhibitor.
- No ongoing cardiac dysrhythmias >Grade 2 NCI CTCAE v4.0, uncontrolled atrial fib (any grade), or QTc interval >470msec.
- Not using meds, herbals, or foods that are potent CYP3A4 inhibitors or inducers (see Appendix V).
- Patients must be adequately recovered from surgery at the time of randomization.
- The minimum time requirement between date of surgery and randomization must be at least 4 weeks (28 days).
- The maximum time requirement between surgery and randomization must be:
- 3 months (90 Days) if no adjuvant chemotherapy was administered
- 8 months (240 Days) if adjuvant chemotherapy was administered
- 10 months (300 Days) if adjuvant chemotherapy and radiation therapy were administered.
- Within 2 wks (preferably w/i 1 wk) pre-randomiz: SGOT & SGPT <2.5x ULN; total serum bili <1.5x ULN; ANC >1500/mm3; platelets >30,000/mm3; Hgb >8.0g/dL; serum creat <2x ULN.
- Pre-randomiz: No non-hematologic toxicity from surg, chemo, or RT >Grade 1 except for alopecia & organ function criteria above.
- Patients must not have any history of locally advanced or metastatic cancer requiring systemic therapy within 5 years from randomization, with the exception of in-situ carcinomas and non-melanoma skin cancer. Patients must have no previous primary lung cancer diagnosed concurrently or within the past 2 years.
- No other investigational agents while on study.
- PRE-STUDY REQUIREMENTS:
- Medical hx, concurrent meds
- PE, perf status, ht, wt, BP, HR
- Liver chemistries (including total bili, SGOT, SGPT, alk phos, total protein, & albumin)
- Serum chemistries (including Na, K, Cl, Ca, Ph, BUN, creat, uric acid, Mg, LDH
- CBC w/diff
- Serum or urine pregnancy test (if applicable, w/i 72 hrs pre-randomiz; sensitivity >50mIU/mL)
- Imaging (baseline chest CT w/i 90 days pre-randomiz)
- Smoking status survey
- Path & Surg reports
- ALK Fusion Status (see bullet 6 above)
- Tumor tissue (fixed or frozen) - MANDATORY & whole blood (optional) for ALCHEMIST
- Serum, plasma, & whole blood (w/pt's consent for future research) - see §10.1
- Signed informed consent.