AzTrials
AzTrials

Neoplasms, ColorectalPhase 1NCT00540943

Study of Pazopanib, Irinotecan and Cetuximab in Combination to Treat 2nd Line Metastatic Colorectal Cancer

A Phase 1 study testing Pazopanib, Cetuximab and Irinotecan in people with Neoplasms, Colorectal, run by GlaxoSmithKline at 2 sites in France.

Completed

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

Official record
Search all trials

Trial summary

Subjects will be entered into cohorts of 3 for the dose escalation phase so that the maximum tolerated dose can be determined. 18 additional patients will be recruited once the maximum tolerated dose (MTD) is determined for disease assessment. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms, Colorectal
What is being tested?
Pazopanib, Cetuximab and Irinotecan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
2 sitesFrance
Study dates
13 Jul 2007to 3 May 2010
Phase
Phase 1
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female at least 18 years of age.
  • Willing and able to sign a written informed consent.
  • Is either affiliated to or a beneficiary of a social security category
  • Histologically or cytologically confirmed diagnosis of colorectal cancer. Subjects should have metastatic disease which is refractory or relapsed following prior treatment.
  • Documented disease progression after prior treatment with 5-FU, oxaliplatin and irinotecan containing regimens.
  • Complete recovery from surgical or radiotherapy procedures.
Show all 27Show fewer
  • Eastern Cooperative Oncology Group performance status of 0 or 1, or Karnofsky score ≥ 70%.
  • Able to swallow and retain oral medications.
  • Adequate bone marrow function (absolute neutrophil count greater than or equal to 1,500/mm3, platelet count greater than or equal to 100,000/mm3, hemoglobin levels greater than or equal to 10g/dL).
  • Adequate renal function as determined by a creatinine clearance greater than 50 mL/minute calculated by the Cockcroft-Gault Formula. Measured creatinine clearance greater than or equal to 50 mL/minute by 24 hour urine collection will be acceptable in lieu of a calculated value.
  • Urine Protein Creatinine (UPC) Ratio of ≤ 1 as assessed in a random or spot urine sample.
  • Adequate hepatic function determined by total bilirubin within the normal range and aspartate aminotransferase (AST or SGOT) or alanine aminotransferase (ALT or SGPT) less than or equal to 2.5 times the upper limit of normal.
  • Prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time (PTT) less than or equal to 1.2 times the ULN.
  • A female subject is eligible to enter and participate in the study if she is:
  • ·Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any woman who:
  • Has had a hysterectomy, or
  • Has had a bilateral oophorectomy (ovariectomy), or
  • Has had a bilateral tubal ligation, or
  • Is post-menopausal (demonstrate total cessation of menses for greater than or equal to 1 year).
  • Childbearing potential, has a negative serum pregnancy test at screening, and agrees to one of the following:
  • An intrauterine device with a documented failure rate of less than 1% per year.
  • Vasectomized partner who is sterile prior to the subject's entry and is the sole sexual partner for that woman.
  • Complete abstinence from sexual intercourse for 14 days before exposure to investigation product, throughout the clinical trial, and for at least 21 days after the last dose of investigational product.
  • Double barrier contraception defined as condom with spermicidal jelly, foam, suppository, or film; OR diaphragm with spermicide; OR male condom and diaphragm.
  • A male patient with a female partner of childbearing potential is eligible to enter and participate in the study if he uses a barrier method of contraception or abstinence during the study.
  • Predicted life expectancy of at least 12 weeks.
  • Able to understand and comply with protocol requirements and instructions and intends to complete the study as planned.

Who cannot join

  • Has participated in any study using an investigational drug during the previous 28 days.
  • Has had any major surgery, chemotherapy, investigational agent, or radiotherapy within the last 28 days and/or not recovered from prior therapy.
  • Any history of grade III toxicity related to prior treatment with anti VEGF compound other than grade 3 hypertension subsequently controlled with antihypertensive agents.
  • Has received prior treatment with pazopanib / investigational anti-angiogenic compounds or cetuximab. Prior treatment with Avastin is permitted. Known contraindications to the use of irinotecan and cetuximab.
  • Unable to tolerate 180mg/m2 of irinotecan every two weeks during previous treatment.
  • Is unable to discontinue prohibited medications, as stipulated in the protocol for 14 days prior to Visit 1 and for the duration of the study
Show all 23Show fewer
  • Has received Amiodarone for arrythmias within the last 6 months prior to Visit 1
  • Has known allergy to penicillin.
  • Women who are pregnant or lactating.
  • Poorly controlled hypertension (systolic blood pressure [SBP] of 140 mmHg or higher, or diastolic blood pressure [DBP] of 90 mmHg or higher). Initiation or adjustment of blood pressure medication is permitted prior to study entry provided the subject has 2 consecutive blood pressure readings less than 140/90 mmHg, each separated by a minimum of 24 hours. These readings need to be collected prior to the first dose.
  • Corrected QT (QTc) prolongation defined as a QTc interval greater than or equal to 480 msec and a prior history of cardiovascular disease, arrhythmias, or significant ECG abnormalities.
  • Has Class III or IV heart failure as defined by the New York Heart Association functional classification system.
  • Arterial thrombi, myocardial infarction, admission for unstable angina, uncontrolled or symptomatic arrhythmia, cardiac angioplasty, or stenting within the last 6 months.
  • Any history of cerebrovascular accident (CVA), or pulmonary embolism within the last 6 months.
  • History of untreated deep venous thrombosis (DVT) within the past 6 months (e.g. calf vein thrombosis). Note: Patients with recent DVT who have been treated with therapeutic anti-coagulant agents (excluding therapeutic warfarin) for at least 6 weeks are eligible.
  • Current use of therapeutic warfarin. NOTE: Low molecular weight heparin and prophylactic low-dose warfarin (no more than 1mg per day) are permitted. PT/PTT and INR must be within 1.2 times the upper limit of normal.
  • Known history of leptomeningeal or brain metastases. NOTE: Computed tomography or magnetic resonance imaging (MRI) scans are not required to rule out central nervous system metastases unless the subject is exhibiting neurologic signs or symptoms. If, however, CT or MRI scans are performed and document central nervous system disease, the subject is ineligible, regardless of whether neurologic signs or symptoms are present.
  • Any serious and/or unstable pre-existing medical, psychiatric, or other condition (including laboratory abnormalities) that could interfere with subject safety or obtaining informed consent.
  • History of mal-absorption syndrome, disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption, distribution, metabolism, or excretion of study drugs.
  • History of any unresolved bowel obstruction or diarrhea.
  • The subject has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug, irinotecan, or cetuximab, unless enrolment is approved by the GSK Medical Monitor following discussion with the Investigator.
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  • Is on any specifically prohibited medication or requires any of these medications during treatment with pazopanib.

Trial locations and contacts

2 sites in 1 country.

France2 sites

  • GSK Investigational Site

    Saint-Herblain, 44805

  • GSK Investigational Site

    Toulouse, 31052

Other trials in France

About this study

Official title: Phase I Study of Safety and Pharmacokinetics of Pazopanib in Combination With Cetuximab and Irinotecan in Patients With Colorectal Cancer

Subjects will be entered into cohorts of 3 for the dose escalation phase so that the maximum tolerated dose can be determined. 18 additional patients will be recruited once the maximum tolerated dose (MTD) is determined for disease assessment.

Being tested
Pazopanib, Cetuximab, Irinotecan
Keywords
cetuximab, irinotecan,, pazopanib,, Colorectal cancer,
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • PazopanibDrug

    Pazopanib is a potent, multi-targeted tyrosine kinase inhibitor of VEGFR-1, -2, -3, PDGFR-alpha and -beta and c-kit.

  • CetuximabDrug

    Cetuximab will be supplied as a single-use 50 milliliter vial containing 100 micrograms of cetuximab as a sterile, preservative-free, injectable liquid at a concentration of 2 milligram per milliliter in phosphate.

    buffered saline

  • IrinotecanDrug

    Irinotecan hydrochloride trihydrate is an antineoplastic agent of the topoisomerase I inhibitor class.

Study groups in NCT00540943
Study groupRoleWhat they receive
Single ArmExperimentalirinotecan and cetuximab in combination with pazopanib.
Receives: Drug: Pazopanib; Drug: Cetuximab; Drug: Irinotecan

What is being measured

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

  1. The safety and tolerability of the maximum tolerated dose defined as a dose regimen where no more than 1 of 6 subjects experiences a dose limiting toxicity.

    Measured: End of 2009

Secondary outcomes (9)

  1. pharmacokinetics disease assessment

    Measured: 2010

  2. Clearance of irinotecan (if data permit) and AUC, Cmax, tmax, and t1/2 of irinotecan and SN-38 after administration of irinotecan plus cetuximab.

    Measured: 2010

  3. AUC(0-24), Cmax, tmax, and t1/2 of pazopanib when administered with irinotecan and cetuximab

    Measured: 2010

  4. AUC(0-24), Cmax, and tmax of cetuximab when administered with irinotecan alone

    Measured: 2010

  5. AUC(0-24), Cmax, and tmax of cetuximab when administered with irinotecan plus pazopanib.

    Measured: 2010

  6. The ratio of SN-38 AUC(0-24) and irinotecan AUC(0-24) on Cycle 1 Day 1 and on Cycle 2 Day 1.

    Measured: 2010

  7. Objective response rate (complete response (CR) plus partial response (PR)) will be the primary measure of antitumor activity

    Measured: 2010

  8. Stable disease (SD) at 4 months

    Measured: 4 months

  9. Time to progression

    Measured: 2010

Timeline

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

  1. First posted8 Oct 2007 (estimated)
  2. Study start13 Jul 2007
  3. Primary completion3 May 2010
  4. Study completion3 May 2010

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00540943
Sponsor's protocol ID
VEG108925
Status last verified
Nov 2017
First submitted
5 Oct 2007
Last updated
29 Nov 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pazopanib, Cetuximab and Irinotecan in people with Neoplasms, Colorectal, run by GlaxoSmithKline at 2 sites in France.

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

Who may be eligible to take part?

The sponsor lists 27 inclusion and 23 exclusion criteria. 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 29 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in France. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The safety and tolerability of the maximum tolerated dose defined as a dose regimen where no more than 1 of 6 subjects experiences a dose limiting toxicity. (time frame: End of 2009). 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 NCT00540943.

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 29 Nov 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in