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

NCT00540943 | Completed Phase 1

• 1 other identifier: VEG108925
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Neoplasms, Colorectal

Keywords

cetuximab; irinotecan,; pazopanib,; Colorectal cancer,

Outcome Measures

Primary Outcomes (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.

  End of 2009

Secondary Outcomes (9)

• pharmacokinetics disease assessment

  2010

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

  2010

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

  2010

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

  2010

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

  2010

Study Arms (1)

Single Arm

EXPERIMENTAL

irinotecan and cetuximab in combination with pazopanib.

Drug: Pazopanib; Drug: Cetuximab; Drug: Irinotecan

Interventions

Pazopanib DRUG

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

Single Arm

Cetuximab DRUG

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

Single Arm

Irinotecan DRUG

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

Single Arm

Eligibility Criteria

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

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Saint-Herblain, 44805, France

Location

GSK Investigational Site

Toulouse, 31052, France

Location

Related Links

• Results for study VEG108925 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

pazopanib; Cetuximab; 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; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2007
• First Posted: October 8, 2007
• Study Start: July 13, 2007
• Primary Completion: May 3, 2010
• Study Completion: May 3, 2010
• Last Updated: November 29, 2017

Record last verified: 2017-11

Locations

FR (2)