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 because the information has not been verified recently.
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
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 Recruiting
Bournemouth, England, United Kingdom, BH7 7DW
Contact: Tamas Hickish, MD    44-120-230-3626    tamas.hickish@rbch.nhs.uk   
Sussex Cancer Centre at Royal Sussex County Hospital Recruiting
Brighton, England, United Kingdom, BN2 5BE
Contact: Andrew Webb, MD    44-12-7369-6955      
Bristol Haematology and Oncology Centre Recruiting
Bristol, England, United Kingdom, BS2 8ED
Contact: Stephen J. Falk, MD    44-117-928-2416    stephen.falk@ubht.nhs.uk   
Addenbrooke's Hospital Recruiting
Cambridge, England, United Kingdom, CB2 2QQ
Contact: Charles B. Wilson, MD    44-1223-217-110    charles.wilson@addenbrookes.nhs.uk   
Gloucestershire Oncology Centre at Cheltenham General Hospital Recruiting
Cheltenham, England, United Kingdom, GL53 7AN
Contact: Kim Benstead, MD    44-845-422-2222    kim.benstead@egnhst.org.uk   
Eastbourne District General Hospital Recruiting
Eastbourne, England, United Kingdom, BN21 2UD
Contact: Fiona McKinna, MD    44-132-341-7400    fiona.mckinna@bsuh.nhs.uk   
St. Luke's Cancer Centre at Royal Surrey County Hospital Recruiting
Guildford, England, United Kingdom, GU2 7XX
Contact: Gary W. Middleton    44-148-357-1122    gmiddleton@royalsurrey.nhs.uk   
Huddersfield Royal Infirmary Recruiting
Huddersfield, West Yorks, England, United Kingdom, HD3 3EA
Contact: Jo Dent    44-1484-342-000      
Hinchingbrooke Hospital Recruiting
Huntingdon, England, United Kingdom, PE18 6NT
Contact: Li Tee Tan, MD    44-1480-416-416      
Airedale General Hospital Recruiting
Keighley, England, United Kingdom, BD20 6TD
Contact: S. Michael Crawford, MD    44-1535-652-511    michael.crawford@anhst.nhs.uk   
Cookridge Hospital Recruiting
Leeds, England, United Kingdom, LS16 6QB
Contact: Matthew T. Seymour, MA, MD, FRCP    44-113-267-3411      
Royal Liverpool University Hospital Recruiting
Liverpool, England, United Kingdom, L7 8XP
Contact: David Smith, MD    44-151-706-2000      
St. Mary's Hospital Recruiting
London, England, United Kingdom, W2 1NY
Contact: Susan Cleator, MD, PhD    44-207-886-6666    s.cleator@imperial.ac.uk   
Queen Elizabeth Hospital - Woolwich Recruiting
London, England, United Kingdom, SE18 4QH
Contact: Nick Maisey    44-208-836-6000    nick.maisey@kcl.ac.uk   
UCL Cancer Institute Recruiting
London, England, United Kingdom, NW3 2PF
Contact: Astrid Mayer, MD    44-207-794-0500    a.mayer@ucl.ac.uk   
Mid Kent Oncology Centre at Maidstone Hospital Recruiting
Maidstone, England, United Kingdom, ME16 9QQ
Contact: Mark Hill, MD    44-1622-729-000      
Clatterbridge Centre for Oncology Recruiting
Merseyside, England, United Kingdom, CH63 4JY
Contact: Sun Myint, MD, FRCP(Edin), DMRT, FFRCS, F    44-151-334-1155    sun.myint@ccotrust.nhs.uk   
James Cook University Hospital Recruiting
Middlesbrough, England, United Kingdom, TS4 3BW
Contact: N. Wadd, MD    44-1642-850-850      
Mount Vernon Cancer Centre at Mount Vernon Hospital Recruiting
Northwood, England, United Kingdom, HA6 2RN
Contact: Robert Glynne-Jones, MD    44-192-382-6111    robglynnejones@nhs.net   
Peterborough Hospitals Trust Recruiting
Peterborough, England, United Kingdom, PE3 6DA
Contact: Karen E. McAdam, MD    44-173-387-4000      
Dorset Cancer Centre Recruiting
Poole Dorset, England, United Kingdom, BH15 2JB
Contact: Tamas Hickish, MD    44-120-266-5511      
Portsmouth Oncology Centre at Saint Mary's Hospital Recruiting
Portsmouth Hants, England, United Kingdom, PO3 6AD
Contact: Ann O'Callaghan, MD    44-23-9228-6000 ext. 2361    ann.o'callaghan@porthosp.nhs.uk   
Cancer Research Centre at Weston Park Hospital Recruiting
Sheffield, England, United Kingdom, S10 2SJ
Contact: Jonathan Wadsley    44-114-226-5000      
South Tyneside District Hospital Recruiting
South Shields, England, United Kingdom, NE34 0PL
Contact: Ashraf Azzabi, MD    44-191-202-4178      
Royal Marsden - Surrey Recruiting
Sutton, England, United Kingdom, SM2 5PT
Contact: Ian Chau, MD    44-208-661-3582      
Great Western Hospital Recruiting
Swindon, England, United Kingdom, SN3 6BB
Contact: Claire Blesing    44-1793-604-020      
Worthing Hospital Recruiting
Worthing, England, United Kingdom, BN11 2DH
Contact: Andrew Webb, MD    44-1903-205-111      
Yeovil District Hospital Recruiting
Yeovil, England, United Kingdom, BA21 4AT
Contact: Stephen J. Falk, MD    44-193-547-5122    stephen.falk@swest.uhs.uk   
Edinburgh Cancer Centre at Western General Hospital Recruiting
Edinburgh, Scotland, United Kingdom, EH4 2XU
Contact: Lesley Dawson    44-131-537-1000      
Ysbyty Gwynedd Recruiting
Bangor, Wales, United Kingdom, LL57 2PW
Contact: Catherine Bale    44-124-838-4384      
Velindre Cancer Center at Velindre Hospital Recruiting
Cardiff, Wales, United Kingdom, CF14 2TL
Contact: Timothy Maughan, MD    44-29-2061-5888      
Glan Clwyd Hospital Recruiting
Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ
Contact: Simon Gollins, MD    44-1745-583-910    simon.gollins@cd-tr.wales.nhs.uk   
South West Wales Cancer Institute Recruiting
Swansea, Wales, United Kingdom, SA2 8QA
Contact: John Wagstaff, MD, MB, ChB, FRCP    44-179-220-2666    profwagstaff@netscape.net   
Sponsors and Collaborators
University of Leeds
Investigators
Study Chair: Matthew T. Seymour, MA, MD, FRCP Cookridge Hospital
  More Information

Additional Information:
No publications provided

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
Cyclosporins
Cyclosporine
Irinotecan
Fluorouracil
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014