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

NCT00389870 | Completed Phase 3

• 6 other identifiers: CDR0000510284CTRU-PICCOLO-MO-05-7289EUDRACT-2005-003492-20CTAAC-CTRU-PICCOLO-MO-05-7289AMGEN-CTRU-PICCOLO-MO-05-7289EU-20647
• Study Type: interventional
• Target: 1,198
• Locations: 1 country
• Sites: 33

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

recurrent colon cancer; stage IV colon cancer; recurrent rectal cancer; stage IV rectal cancer; adenocarcinoma of the colon; adenocarcinoma of the rectum

Outcome Measures

Primary Outcomes (2)

• Proportion of patients treated with irinotecan hydrochloride (Ir) alone vs Ir and cyclosporine (IrC) who are progression-free at 12 weeks

• Overall survival of patients treated with Ir vs Ir and panitumumab (IrP) and no prior cetuximab

Secondary Outcomes (8)

• Proportion of patients free from treatment failure at 12 weeks in patients treated with Ir vs IrC

• Overall survival in patients treated with Ir vs IrC

• Nurse-assessed toxicity (all-cause mortality, diarrhea ≥ grade 3 at 12 weeks) in patients treated with Ir vs IrC

• Progression-free at 12 weeks in patients treated with Ir vs IrP and no prior cetuximab

• Nurse assessed toxicity (all-cause mortality) in patients treated with Ir vs IrP and no prior cetuximab

Interventions

panitumumab BIOLOGICAL

cyclosporine DRUG

irinotecan hydrochloride DRUG

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Leeds: lead

Study Sites (33)

Royal Bournemouth Hospital

Bournemouth, England, BH7 7DW, United Kingdom

Location

Sussex Cancer Centre at Royal Sussex County Hospital

Brighton, England, BN2 5BE, United Kingdom

Location

Bristol Haematology and Oncology Centre

Bristol, England, BS2 8ED, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, England, CB2 2QQ, United Kingdom

Location

Gloucestershire Oncology Centre at Cheltenham General Hospital

Cheltenham, England, GL53 7AN, United Kingdom

Location

Eastbourne District General Hospital

Eastbourne, England, BN21 2UD, United Kingdom

Location

St. Luke's Cancer Centre at Royal Surrey County Hospital

Guildford, England, GU2 7XX, United Kingdom

Location

Huddersfield Royal Infirmary

Huddersfield, West Yorks, England, HD3 3EA, United Kingdom

Location

Hinchingbrooke Hospital

Huntingdon, England, PE18 6NT, United Kingdom

Location

Airedale General Hospital

Keighley, England, BD20 6TD, United Kingdom

Location

Cookridge Hospital

Leeds, England, LS16 6QB, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, England, L7 8XP, United Kingdom

Location

UCL Cancer Institute

London, England, NW3 2PF, United Kingdom

Location

Queen Elizabeth Hospital - Woolwich

London, England, SE18 4QH, United Kingdom

Location

St. Mary's Hospital

London, England, W2 1NY, United Kingdom

Location

Mid Kent Oncology Centre at Maidstone Hospital

Maidstone, England, ME16 9QQ, United Kingdom

Location

Clatterbridge Centre for Oncology

Merseyside, England, CH63 4JY, United Kingdom

Location

James Cook University Hospital

Middlesbrough, England, TS4 3BW, United Kingdom

Location

Mount Vernon Cancer Centre at Mount Vernon Hospital

Northwood, England, HA6 2RN, United Kingdom

Location

Peterborough Hospitals Trust

Peterborough, England, PE3 6DA, United Kingdom

Location

Dorset Cancer Centre

Poole Dorset, England, BH15 2JB, United Kingdom

Location

Portsmouth Oncology Centre at Saint Mary's Hospital

Portsmouth Hants, England, PO3 6AD, United Kingdom

Location

Cancer Research Centre at Weston Park Hospital

Sheffield, England, S10 2SJ, United Kingdom

Location

South Tyneside District Hospital

South Shields, England, NE34 0PL, United Kingdom

Location

Royal Marsden - Surrey

Sutton, England, SM2 5PT, United Kingdom

Location

Great Western Hospital

Swindon, England, SN3 6BB, United Kingdom

Location

Worthing Hospital

Worthing, England, BN11 2DH, United Kingdom

Location

Yeovil District Hospital

Yeovil, England, BA21 4AT, United Kingdom

Location

Edinburgh Cancer Centre at Western General Hospital

Edinburgh, Scotland, EH4 2XU, United Kingdom

Location

Ysbyty Gwynedd

Bangor, Wales, LL57 2PW, United Kingdom

Location

Velindre Cancer Center at Velindre Hospital

Cardiff, Wales, CF14 2TL, United Kingdom

Location

Glan Clwyd Hospital

Rhyl, Denbighshire, Wales, LL 18 5UJ, United Kingdom

Location

South West Wales Cancer Institute

Swansea, Wales, SA2 8QA, United Kingdom

Location

Related Publications (3)

• Seymour MT, Brown SR, Middleton G, Maughan T, Richman S, Gwyther S, Lowe C, Seligmann JF, Wadsley J, Maisey N, Chau I, Hill M, Dawson L, Falk S, O'Callaghan A, Benstead K, Chambers P, Oliver A, Marshall H, Napp V, Quirke P. Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial. Lancet Oncol. 2013 Jul;14(8):749-59. doi: 10.1016/S1470-2045(13)70163-3. Epub 2013 May 29.

  PMID: 23725851 RESULT

• Middleton G, Brown S, Lowe C, Maughan T, Gwyther S, Oliver A, Richman S, Blake D, Napp V, Marshall H, Wadsley J, Maisey N, Chau I, Hill M, Gollins S, Myint S, Slater S, Wagstaff J, Bridgewater J, Seymour M. A randomised phase III trial of the pharmacokinetic biomodulation of irinotecan using oral ciclosporin in advanced colorectal cancer: results of the Panitumumab, Irinotecan & Ciclosporin in COLOrectal cancer therapy trial (PICCOLO). Eur J Cancer. 2013 Nov;49(16):3507-16. doi: 10.1016/j.ejca.2013.06.017. Epub 2013 Aug 13.

  PMID: 23953030 RESULT

• Seligmann JF, Elliott F, Richman SD, Jacobs B, Hemmings G, Brown S, Barrett JH, Tejpar S, Quirke P, Seymour MT. Combined Epiregulin and Amphiregulin Expression Levels as a Predictive Biomarker for Panitumumab Therapy Benefit or Lack of Benefit in Patients With RAS Wild-Type Advanced Colorectal Cancer. JAMA Oncol. 2016 May 1;2(5):633-642. doi: 10.1001/jamaoncol.2015.6065.

  PMID: 26867820 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Panitumumab; Cyclosporine; Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Matthew T. Seymour, MA, MD, FRCP

  Cookridge Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 18, 2006
• First Posted: October 19, 2006
• Study Start: December 1, 2006
• Last Updated: June 1, 2022

Record last verified: 2022-05

Locations

GB (33)