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Colorectal CancerPhase 3NCT00389870

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

A Phase 3 study testing panitumumab, cyclosporine and irinotecan hydrochloride in people with Colorectal Cancer, run by University of Leeds at 33 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Colorectal Cancer
What is being tested?
panitumumab, cyclosporine and irinotecan hydrochloride
How many people
1,198 participants
Where
33 sitesUnited Kingdom
Study dates
Dec 2006to not given
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

33 sites in 1 country.

33 sites in 1 country

United Kingdom33 sites

  • Ysbyty Gwynedd

    Bangor, Wales, LL57 2PW

  • Royal Bournemouth Hospital

    Bournemouth, England, BH7 7DW

  • Sussex Cancer Centre at Royal Sussex County Hospital

    Brighton, England, BN2 5BE

  • Bristol Haematology and Oncology Centre

    Bristol, England, BS2 8ED

  • Addenbrooke's Hospital

    Cambridge, England, CB2 2QQ

  • Velindre Cancer Center at Velindre Hospital

    Cardiff, Wales, CF14 2TL

  • Gloucestershire Oncology Centre at Cheltenham General Hospital

    Cheltenham, England, GL53 7AN

  • Eastbourne District General Hospital

    Eastbourne, England, BN21 2UD

  • Edinburgh Cancer Centre at Western General Hospital

    Edinburgh, Scotland, EH4 2XU

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

    Guildford, England, GU2 7XX

  • Huddersfield Royal Infirmary

    Huddersfield, West Yorks, England, HD3 3EA

  • Hinchingbrooke Hospital

    Huntingdon, England, PE18 6NT

  • Airedale General Hospital

    Keighley, England, BD20 6TD

  • Cookridge Hospital

    Leeds, England, LS16 6QB

  • Royal Liverpool University Hospital

    Liverpool, England, L7 8XP

  • UCL Cancer Institute

    London, England, NW3 2PF

  • Queen Elizabeth Hospital - Woolwich

    London, England, SE18 4QH

  • St. Mary's Hospital

    London, England, W2 1NY

  • Mid Kent Oncology Centre at Maidstone Hospital

    Maidstone, England, ME16 9QQ

  • Clatterbridge Centre for Oncology

    Merseyside, England, CH63 4JY

  • James Cook University Hospital

    Middlesbrough, England, TS4 3BW

  • Mount Vernon Cancer Centre at Mount Vernon Hospital

    Northwood, England, HA6 2RN

  • Peterborough Hospitals Trust

    Peterborough, England, PE3 6DA

  • Dorset Cancer Centre

    Poole Dorset, England, BH15 2JB

  • Portsmouth Oncology Centre at Saint Mary's Hospital

    Portsmouth Hants, England, PO3 6AD

  • Glan Clwyd Hospital

    Rhyl, Denbighshire, Wales, LL 18 5UJ

  • Cancer Research Centre at Weston Park Hospital

    Sheffield, England, S10 2SJ

  • South Tyneside District Hospital

    South Shields, England, NE34 0PL

  • Royal Marsden - Surrey

    Sutton, England, SM2 5PT

  • South West Wales Cancer Institute

    Swansea, Wales, SA2 8QA

  • Great Western Hospital

    Swindon, England, SN3 6BB

  • Worthing Hospital

    Worthing, England, BN11 2DH

  • Yeovil District Hospital

    Yeovil, England, BA21 4AT

Other trials in United Kingdom

About this study

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)]

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.

Read the 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.

Being tested
panitumumab, cyclosporine, irinotecan hydrochloride
Keywords
recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum
Medical subject headings
Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

Secondary outcomes (8)

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

  2. Overall survival in patients treated with Ir vs IrC

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

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

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

  6. Progression-free survival in patients treated with Ir vs IrP and prior cetuximab

  7. Best response at 1 year in patients treated with Ir vs IrP and prior cetuximab

  8. Patient-assessed symptom/quality of life/acceptability scores at 12 and 24 weeks in patients treated with Ir vs IrP and prior cetuximab

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2006 (estimated)
  2. Study startDec 2006

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Masking
None (open label)
Enrolment
1,198 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00389870
Sponsor's protocol ID
CDR0000510284
Other IDs
CTRU-PICCOLO-MO-05-7289, EUDRACT-2005-003492-20, CTAAC-CTRU-PICCOLO-MO-05-7289, AMGEN-CTRU-PICCOLO-MO-05-7289, EU-20647
Status last verified
May 2022
First submitted
18 Oct 2006
Last updated
1 Jun 2022
Results posted
No

Publications

  • 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.

    PubMed 23725851

  • 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.

    PubMed 23953030

  • 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.

    PubMed 26867820

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing panitumumab, cyclosporine and irinotecan hydrochloride in people with Colorectal Cancer, run by University of Leeds at 33 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients treated with irinotecan hydrochloride (Ir) alone vs Ir and cyclosporine (IrC) who are progression-free at 12 weeks. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00389870, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2022.

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