Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Irinotecan With or Without Panitumumab or Cyclosporine in Treating Patients With Advanced or Metastatic Colorectal Cancer That Did Not Respond to Fluorouracil

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified July 2007 by National Cancer Institute (NCI).
Recruitment status was:  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00389870
First received: October 18, 2006
Last updated: August 23, 2013
Last verified: July 2007
  Purpose

RATIONALE: Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cyclosporine may help irinotecan work better by making tumor cells more sensitive to the drug. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Panitumumab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether irinotecan is more effective when given with or without panitumumab or cyclosporine in treating colorectal cancer.

PURPOSE: This randomized phase III trial is studying irinotecan to compare how well it works when given with or without panitumumab or cyclosporine in treating patients with advanced or metastatic colorectal cancer that did not respond to fluorouracil.


Condition Intervention Phase
Colorectal Cancer
Biological: panitumumab
Drug: cyclosporine
Drug: irinotecan hydrochloride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised Clinical Trial of Treatment for Fluorouracil-Resistant Advanced Colorectal Cancer Comparing Standard Single-Agent Irinotecan Versus Irinotecan Plus Panitumumab and Versus Irinotecan Plus Ciclosporin [Panitumumab, Irinotecan & Ciclosporin in COLOrectal Cancer Therapy (PICCOLO)]

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of patients treated with irinotecan hydrochloride (Ir) alone vs Ir and cyclosporine (IrC) who are progression-free at 12 weeks [ Designated as safety issue: No ]
  • Overall survival of patients treated with Ir vs Ir and panitumumab (IrP) and no prior cetuximab [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients free from treatment failure at 12 weeks in patients treated with Ir vs IrC [ Designated as safety issue: No ]
  • Overall survival in patients treated with Ir vs IrC [ Designated as safety issue: No ]
  • Nurse-assessed toxicity (all-cause mortality, diarrhea ≥ grade 3 at 12 weeks) in patients treated with Ir vs IrC [ Designated as safety issue: Yes ]
  • Progression-free at 12 weeks in patients treated with Ir vs IrP and no prior cetuximab [ Designated as safety issue: No ]
  • Nurse assessed toxicity (all-cause mortality) in patients treated with Ir vs IrP and no prior cetuximab [ Designated as safety issue: Yes ]
  • Progression-free survival in patients treated with Ir vs IrP and prior cetuximab [ Designated as safety issue: No ]
  • Best response at 1 year in patients treated with Ir vs IrP and prior cetuximab [ Designated as safety issue: No ]
  • Patient-assessed symptom/quality of life/acceptability scores at 12 and 24 weeks in patients treated with Ir vs IrP and prior cetuximab [ Designated as safety issue: No ]

Estimated Enrollment: 1269
Study Start Date: December 2006
Estimated Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Compare the efficacy and toxicity of single-agent irinotecan hydrochloride (Ir) vs Ir with cyclosporine (IrC) in patients with fluorouracil-resistant advanced colorectal cancer.
  • Compare the efficacy of single-agent Ir vs Ir with panitumumab (IrP) in these patients.

Secondary

  • Correlate the toxicity of Ir and/or IrC with genetic variability in the enzymes involved in irinotecan hydrochloride's disposition pathway.
  • Compare IrC to Ir and its metabolites (SN38; SN38G), in terms of pharmacokinetic profile.
  • Correlate the benefit of IrP with tumor expression of epidermal growth factor receptor (EGFR) or its known down-stream molecules as a predictive measure.
  • Correlate IrP efficacy or toxicity (specifically the severity of skin rash) with somatic alterations in the EGFR gene and/or with germline variability in related genes.

OUTLINE: This is a randomized, open-label, controlled, multicenter study. Patients are stratified according to prior cetuximab (yes vs no). Patients are randomized to 1 of 3 treatment arms.

  • Arm I: Patients receive irinotecan hydrochloride IV over 30-90 minutes on day 1.
  • Arm II: Patients receive irinotecan hydrochloride IV over 15-40 minutes on day 1 and oral cyclosporine three times a day on days 1-3.
  • Arm III: Patients receive panitumumab IV over 30-90 minutes followed by irinotecan hydrochloride IV over 30-90 minutes on day 1. Single-agent panitumumab may be continued during breaks in chemotherapy treatment.

In all arms, treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease may continue treatment in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and at 12 and 24 weeks.

After completion of study treatment, patients are followed every 12 weeks for 1 year.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 1,269 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of colorectal adenocarcinoma meeting 1 of the following criteria:

    • Previous or current histologically confirmed primary adenocarcinoma of the colon or rectum and clinical/radiological evidence of advanced or metastatic disease
    • Histologically or cytologically confirmed metastatic adenocarcinoma with clinical or radiological evidence of colorectal primary tumor
  • Unidimensionally measurable disease
  • Disease progression during or after prior fluorouracil with or without oxaliplatin therapy and/or with or without bevacizumab

    • Adjuvant therapy and/or prior therapy for advanced disease allowed
  • No clinical or radiological evidence of pleural effusion or ascites causing ≥ grade 2 dyspnea
  • No clinical or radiological evidence of biliary obstruction
  • No known CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • Life expectancy ≥ 12 weeks
  • Hemoglobin > 10.0 g/dL
  • WBC > 3,000/mm³
  • Platelet count > 100,000/mm³
  • Glomerular filtration rate > 50 mL/min OR EDTA clearance > 60 mL/min
  • Bilirubin < 1.46 mg/dL
  • Alkaline phosphatase ≤ 5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • No history of Gilbert's syndrome
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after completion of study treatment
  • Capable of completing quality of life questionnaires
  • No prior anaphylactic allergic reaction to cetuximab
  • No other prior or concurrent cancer (excluding nonmelanomatous skin cancer)
  • No unresolved bowel obstruction, uncontrolled gastrointestinal infection, chronic enteropathy (e.g., Crohn's disease or ulcerative colitis), or chronic diarrhea (≥ 4 stools per day) of any cause
  • No recent history of seizures
  • No clinical or radiological evidence of interstitial pneumonitis or pulmonary fibrosis,
  • Capable of reliable oral self-medication
  • No other condition that would make the patient unsuitable for participation in this study

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No major thoracic or abdominal surgery within the past 4 weeks
  • No systemic anticancer therapy within the past 3 weeks
  • No prior irinotecan hydrochloride
  • No grapefruit juice within 3 days before and after each chemotherapy treatment
  • No experimental drug therapy or antibody therapy, other than cetuximab, within the past 6 weeks
  • No systemic chemotherapy and/or cetuximab within the past 3 weeks
  • No antifungals or antibiotics within the past 5 days
  • No ongoing requirement for cyclosporine or any other medication including, but not limited to, the following:

    • Ketoconazole, fluconazole, itraconazole
    • Erythromycin, clarithromycin, norfloxacin
    • Diltiazem hydrochloride, verapamil, amiodarone hydrochloride
    • Fluvoxamine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00389870

Locations
United Kingdom
Royal Bournemouth Hospital
Bournemouth, England, United Kingdom, BH7 7DW
Sussex Cancer Centre at Royal Sussex County Hospital
Brighton, England, United Kingdom, BN2 5BE
Bristol Haematology and Oncology Centre
Bristol, England, United Kingdom, BS2 8ED
Addenbrooke's Hospital
Cambridge, England, United Kingdom, CB2 2QQ
Gloucestershire Oncology Centre at Cheltenham General Hospital
Cheltenham, England, United Kingdom, GL53 7AN
Eastbourne District General Hospital
Eastbourne, England, United Kingdom, BN21 2UD
St. Luke's Cancer Centre at Royal Surrey County Hospital
Guildford, England, United Kingdom, GU2 7XX
Huddersfield Royal Infirmary
Huddersfield, West Yorks, England, United Kingdom, HD3 3EA
Hinchingbrooke Hospital
Huntingdon, England, United Kingdom, PE18 6NT
Airedale General Hospital
Keighley, England, United Kingdom, BD20 6TD
Cookridge Hospital
Leeds, England, United Kingdom, LS16 6QB
Royal Liverpool University Hospital
Liverpool, England, United Kingdom, L7 8XP
UCL Cancer Institute
London, England, United Kingdom, NW3 2PF
Queen Elizabeth Hospital - Woolwich
London, England, United Kingdom, SE18 4QH
St. Mary's Hospital
London, England, United Kingdom, W2 1NY
Mid Kent Oncology Centre at Maidstone Hospital
Maidstone, England, United Kingdom, ME16 9QQ
Clatterbridge Centre for Oncology
Merseyside, England, United Kingdom, CH63 4JY
James Cook University Hospital
Middlesbrough, England, United Kingdom, TS4 3BW
Mount Vernon Cancer Centre at Mount Vernon Hospital
Northwood, England, United Kingdom, HA6 2RN
Peterborough Hospitals Trust
Peterborough, England, United Kingdom, PE3 6DA
Dorset Cancer Centre
Poole Dorset, England, United Kingdom, BH15 2JB
Portsmouth Oncology Centre at Saint Mary's Hospital
Portsmouth Hants, England, United Kingdom, PO3 6AD
Cancer Research Centre at Weston Park Hospital
Sheffield, England, United Kingdom, S10 2SJ
South Tyneside District Hospital
South Shields, England, United Kingdom, NE34 0PL
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT
Great Western Hospital
Swindon, England, United Kingdom, SN3 6BB
Worthing Hospital
Worthing, England, United Kingdom, BN11 2DH
Yeovil District Hospital
Yeovil, England, United Kingdom, BA21 4AT
Edinburgh Cancer Centre at Western General Hospital
Edinburgh, Scotland, United Kingdom, EH4 2XU
Ysbyty Gwynedd
Bangor, Wales, United Kingdom, LL57 2PW
Velindre Cancer Center at Velindre Hospital
Cardiff, Wales, United Kingdom, CF14 2TL
Glan Clwyd Hospital
Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ
South West Wales Cancer Institute
Swansea, Wales, United Kingdom, SA2 8QA
Sponsors and Collaborators
University of Leeds
Investigators
Study Chair: Matthew T. Seymour, MA, MD, FRCP Cookridge Hospital
  More Information

ClinicalTrials.gov Identifier: NCT00389870     History of Changes
Other Study ID Numbers: CDR0000510284  CTRU-PICCOLO-MO-05-7289  EUDRACT-2005-003492-20  CTAAC-CTRU-PICCOLO-MO-05-7289  AMGEN-CTRU-PICCOLO-MO-05-7289  EU-20647 
Study First Received: October 18, 2006
Last Updated: August 23, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent colon cancer
stage IV colon cancer
recurrent rectal cancer
stage IV rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Camptothecin
Fluorouracil
Cyclosporins
Cyclosporine
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on December 09, 2016