Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information

Alternate Title

Immediate Compared With Delayed Combination Chemotherapy in Treating Colorectal Cancer Patients With Resected Liver or Lung Metastases

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	any age		CAN-NCIC-CO7 CNR-GIVIO-CO3, EORTC-40923, NCI-V94-0464, CO7

Objectives

I.  Compare overall and disease-free survival and quality of life in patients 
with metastatic colorectal cancer who are clinically free of disease by 
surgical resection of liver or lung metastases and randomized to immediate 
adjuvant chemotherapy with fluorouracil/l-leucovorin (5-FU/L-CF) vs. 5-FU/L-CF 
delayed until development of unresectable metastatic disease.

Entry Criteria

Disease Characteristics:

Primary adenocarcinoma of the colon, rectum, or rectosigmoid space with either
liver or lung metastases
  Distal extent of tumor is at least 3 cm from anal verge

  More than 1 synchronous or metachronous primary colorectal tumor allowed

  No more than 4 metastatic lesions involving either liver or lung (but not
  both) allowed

Patient rendered clinically free of disease by one of the following:
  Resection of primary and 1 or more synchronous metastatic lesions during
  same operation

  Resection of primary and 1 or more synchronous metastatic lesions during a
  separate (either prior or subsequent) operative procedure

  Resection of 1 or more metachronous metastatic lesions subsequent to
  complete excision of the primary

Histologically confirmed negative resection margins required for both primary
and metastatic tumors

Involvement of an adjacent organ by direct extension of the primary tumor or
liver or lung metastasis allowed if removed en bloc with the primary tumor or
liver or lung metastasis

Involved regional lymph nodes removed en bloc with the primary tumor allowed
  No distant lymph node metastases, including:
     Porta hepatis
     Mediastinal nodes

No known gross residual disease

No more than 49 days between most recent resection of metastases and
randomization

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  No prior chemotherapy except adjuvant treatment for primary tumor
  At least 6 months between completion of adjuvant chemotherapy and diagnosis
     of metastatic disease

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior radiotherapy except:
     Radiotherapy as a single-modality adjuvant treatment for the primary
     tumor, with diagnosis and resection of eligible metastatic disease at any
     time following radiotherapy

     Neoadjuvant radiotherapy to the primary tumor, with subsequent complete
     resection of primary and either liver or lung metastases

     Cases for which 2-stage treatment is preferable for patient safety when a
     primary rectal tumor and eligible metastasis are diagnosed (i.e.,
     resection of primary, postoperative radiotherapy, and subsequent
     resection of metastases)

  No concurrent radiotherapy

Surgery:
  Prior resection of liver or lung metastases required

Patient Characteristics:

Age:
  Any age

Performance status:
  ECOG 0-2

Hematopoietic:
  WBC at least 4,000
  Platelets at least 100,000

Hepatic:
  Bilirubin no greater than 1.5 x ULN
  SGOT and SGPT no greater than 2.5 x ULN
  Alkaline phosphatase no greater than 2.5 x ULN

Renal:
  Not specified

Other:
  No medical condition that would substantially increase risk from
     chemotherapy
  No prior or concurrent second malignancy except:
     Adequately treated nonmelanomatous skin cancer
     Adequately treated in situ carcinoma of the cervix
  No pregnant or nursing women
  Effective contraception required of fertile patients

Expected Enrollment

478 patients will be entered over 4 years.

Outline

Randomized, unblinded study.

Arm I:  Single-Agent Chemotherapy with Drug Modulation.  Fluorouracil, 5-FU, 
NSC-19893; with L-leucovorin, L-CF.

Arm II:  Observation followed by Single-Agent Chemotherapy with Drug 
Modulation.  Observation until development of unresectable recurrence; 
followed by 5-FU; with L-CF.

Langer B, Bleiberg H, Labianca R, et al.: Fluorouracil (FU) plus l-leucovorin (l-LV) versus observation after potentially curative resection of liver or lung metastases from colorectal cancer (CRC): results of the ENG (EORTC/NCIC CTG/GIVIO) randomized trial. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-592, 2002.

Mitry E, Fields AL, Bleiberg H, et al.: Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol 26 (30): 4906-11, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCIC-Clinical Trials Group

Anthony Fields, MD, FRCPC, Protocol chair		Ph: 780-432-8756 Email: alaf@cancerboard.ab.ca

European Organization for Research and Treatment of Cancer

Harry Bleiberg, MD, Protocol chair		Ph: 32-2-541-3196 Email: harry.bleiberg@bordet.be

European Institute of Oncology

Roberto Labianca, MD, Protocol chair		Ph: 39-2-4022-2241