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CTSU NCCTG N0147 - "A Randomized Phase III Trial of Oxaliplatin (OXAL) Plus 5-Fluorouracil (5-FU)/Leucovorin (CF) with or without Cetuximab (C225) after Curative Resection for Patients with Stage III Colon Cancer"
Treatment Plan (Supplied Drugs: Oxaliplatin & Cetuximab)
EFFECTIVE 10/24/08: TEMPORARILY CLOSED TO ACCRUAL FOR PTS >AGE 70 DUE TO INCREASED TOXICITY ON CETUXIMAB-CONTAINING ARM OF THE TRIAL.
ARM B & ARM C CLOSED TO ACCRUAL AS OF 6/1/05. PTS WHO STAY ON STUDY MUST CROSSOVER TO ARM A & COMPLETE REMAINING CYCLES OF THERAPY PER PROTOCOL.
ARM E & ARM F CLOSED TO ACCRUAL AS OF 6/1/05. PTS WHO STAY ON STUDY MUST CROSSOVER TO ARM D & COMPLETE REMAINING CYCLES OF THERAPY PER PROTOCOL.
See protocol for info on concurrent administration of drugs and hydration.
PRE-RANDOMIZATION
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Blood Draw (following Pre-Randomiz, but prior to start of tx)
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RANDOMIZATION
Arm A - FOLFOX - Oxaliplatin + 5-FU/Leucovorin Regimen (Day 1 of each cycle; q2wks x 12)
Any pts crossing over from Arms B or C must receive a total of 24 wks of protocol therapy.
Leucovorin L (200mg) may be substituted for Leucovorin D.
Oxaliplatin: 85mg/m2, IV in 500ml D5W over 120 mins
Leucovorin: 400mg/m2, IV in 250ml D5W over 120 mins
5-FU: 400mg/m2, IV push
5-FU: 2400mg/m2, IV via ambulatory pump over 46-48 hrs (after Leucovorin)
Arm D - FOLFOX + C225 - Oxaliplatin + 5-FU/Leucovorin + Cetuximab Regimen (q2wks x 12)
Any pts crossing over from Arms E or F must receive a total of 24 wks of protocol therapy.
Leucovorin L (200mg) may be substituted for Leucovorin D.
Cetuximab: 400mg/m2, IV over 2 hrs, Day 1, Tx Week 1 (give b/f chemo)
Cetuximab: 250mg/m2, IV over 1 hr (undiluted 2mg/ml), Day 8, Tx Week 2 (give b/f chemo)
Oxaliplatin: 85mg/m2, IV in 500ml D5W, over 120 mins, Day 1
Leucovorin: 400mg/m2 IV in 250ml D5W, over 120 mins, Day 1
5-FU: 400mg/m2, IV push, Day 1
5-FU: 2400mg/m2, IV via ambulatory pump over 46-48 hrs, Day 1
Subsequent Cycles (Cycles 2-12)
Cetuximab: 250mg/m2, IV over 1 hr (undiluted 2mg/ml), Days 1 & 8 (give b/f chemo)
Oxaliplatin, Leucovorin, & 5-FU as outlined above.
Eligibility
PRE-RANDOMIZATION
Histol-documented colon adenocarcinoma. Gross inferior (caudad) margin of prim tumor must be >12cm from anal verge by rigid proctoscopy. Rigid proctoscopy performed only in those settings where it is important to establish if tumor is a rectal or colon tumor. Stg III tumor must have been completely resected. No Stg IV pts. If tumor adherence to adjacent structures, en bloc resection must be documented in oper report. Pts w/tumor-related obstruction or colonic perforation are eligible.
NOTE: Evidence of EGFR in resected tumor is NOT required.
NOTE: >1 synchronous prim colon cancer is allowed. Staging classification will be based on more advanced prim tumor.
NOTE: Pts w/positive radial (serosal, circumferential) margins are eligible if there is no evidence that surgeon cut through tumor; no evidence that tumor invaded adjacent tissues; & entire specimen was resected en bloc.
>1 path-confirmed positive lymph node.
No evidence of residual involved lymph node disease. >1 lymph node must be found in path specimen. Recommended number of identified nodes is >4.
ECOG perf status 0-2.
Age >18.
English-speaking participants must be able to complete questionnaires by themselves or w/assistance.
Must be willing to provide blood and tissue samples for eligibility and research. Pt has the right to later w/d consent for research studies on blood &/or tissue specimens.
No pregnant or nursing women. Men/Women of childbearing potential must use effective contraception.
No distant mets at regist.
No prior chemo or RT for tx of this malignancy.
No prior therapy w/agent(s) directed against EGFR.
No prior allergic reaction (known sensitivity) to chimerized or murine monoclonal antibody therapy or documented presence of human anti-mouse antibodies.
No previous or concurrent malignancy except treated non-melanoma skin cancer, in situ cervical cancer, or lobular carcinoma in situ in 1 breast, or other cancer disease-free >5 yrs.
No uncontrolled high BP, unstable angina, symptomatic CHF, MI <6 mos pre-randomiz, NYHA class III or IV, symptomatic pulmonary fibrosis or interstitial pneumonitis, active uncontrolled bacterial or viral infection (including HIV or clinically defined AIDS), or systemic fungal infection.
No other medical condition to make protocol unreasonably hazardous for pt (investigator's opinion).
No clinically significant peripheral neuropathy at randomiz (CTCAE v3.0 >Grade 2) neurosensory or neuromotor toxicity.
No concurrent use of other anti-cancer therapy.
No known allergy to other platinum compounds.
No hx of GI bleeding that has not been appropriately addressed (investigator's opinion).
PRESTUDY REQUIREMENTS:
PE (wt, perf status, ht, medical hx)*
CBC, diff, platelets*
Serum chem (alk phos, SGOT, total bili, creat, Na, K, Cl, bicarb CO2, BUN, Mg)*
PT (only pts taking Coumadin)*
CXR or Chest CT (use same method throughout; documentation of recur or new prim is required to be submitted)**
Abdominal US, CT, or MRI**
Pt & Physician Fact Sheet
Translational Research Blood Draw (contact KCCOP for kits)*@
Paraffin-Embedded Tissue Collection# (during primary surgery)
Pt Completed Questionnaires (prior to tx Cycle 1)
Serum Pregnancy Test (if applicable, <7 days pre-randomiz)***
# Paraffin-Embedded Blocks & Slides:
1) ALL diagnostic slides from the resection including those that document extent of disease, radial margin (if positive), those that interface w/adjacent mucosa &/or pre-existing adenoma, and normal colonic mucosa (w/corresponding paraffin block). Submission of 1 block or slide is not adequate for this review.
2) >1 slide documenting nodal mets
3) >3 (4 preferable) blocks to correspond w/submitted slides
4) 1 paraffin-embedded block w/normal colonic mucosa away from tumor (>10cm away or from a negative margin)
5) See protocol if unable to release blocks.
@ Blood: 30ml whole blood in 3 vacutainer tubes (2 lavender top [EDTA] and 1 red top). Forward blood to Mayo Central Lab for Clinical Trials via kits and prepaid mailers.
* <14 days pre-randomiz. For Translational Research Blood draw, samples must be collected following pre-randomiz, but prior to start of tx.
** Within 8 wks pre-randomiz.
*** Recommended that all blood draws (serum pregnancy & eligibility bloods) both be drawn <7 days pre-randomiz.
Signed informed consent.
RANDOMIZATION
Randomization must occur <56 days post-surg.
<14 days pre-randomiz: Hgb >9gl/dL, ANC >LNL (e.g., 1500/mm3), platelets >100,000/µL, creat & total bili each <1.5x UNL..
Negative serum pregnancy test <7 days pre-randomiz (only women of childbearing potential).