Safety Study of the Combination of Panitumumab, Irinotecan and Everolimus in the Treatment of Advanced Colorectal Cancer

NCT01139138 | Completed Phase 1

• 1 other identifier: AU-2009-0003/CRAD001CAU06T
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the safety of panitumumab, irinotecan and everolimus when given in combination to treat advanced colorectal cancer

Conditions

Colorectal Cancer; Colorectal Carcinoma; Colorectal Tumors; Neoplasms, Colorectal

Keywords

Colorectal Cancer; Colorectal Carcinoma; Colorectal Tumors; Neoplasms, Colorectal

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicities

  To determine the maximum tolerated dose (MTD)of everolimus, irinotecan and panitumumab when given in combination for patients with Kras WT mCRC

  at end of cycle 2 (each cycle is 14 days)

Secondary Outcomes (4)

• Safety & toxicity

  Approximately 24 weeks

• Response rate

  Assessed every 6 weeks until disease progression

• Progression free survival

  Until disease progression, occurrence of new disease or death

• Overall Survival

  Assessed 3 monthly until death

Study Arms (1)

Panitumumab + Irinotecan + Everolimus

EXPERIMENTAL

Drug: Panitumumab; Drug: Irinotecan; Drug: Everolimus

Interventions

Panitumumab DRUG

Panitumumab 6mg/kg IV every 14 days

Also known as: Vectibix

Panitumumab + Irinotecan + Everolimus

Irinotecan DRUG

Irinotecan 200mg/m2 IV every 14 days

Panitumumab + Irinotecan + Everolimus

Everolimus DRUG

Everolimus daily po (dosage varies with cohort)

Also known as: RAD001

Panitumumab + Irinotecan + Everolimus

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years
• Histological diagnosis of colorectal cancer that is KRAS wild type
• Metastatic disease not amenable to resection
• Measurable disease as assessed by CT scan using RECIST criteria
• Received and failed fluoropyrimidine therapy
• Radiographically documented disease progression per RECIST criteria
• For phase 1b group only, ECOG PS 0-1
• For phase 2 group only, ECOG PS 0-2
• Adequate bone marrow function with haemoglobin \> 100 g/L, platelets \> 100 X 109/l; neutrophils \> 1.5 X 109/l within 7 days of enrolment
• Adequate renal function, with calculated creatinine clearance \>40 ml/min (Cockcroft and Gault) within 7 days of enrolment
• Adequate hepatic function with serum total bilirubin \< 1.25 X upper limit of normal range and ALT or AST\<2.5xULN (\<5xULN if liver metastases present) within 7 days of enrolment
• Magnesium ≥ lower limit of normal within 7 days of enrolment.
• Fasting serum cholesterol ≤ 7.75mmol/L AND fasting triglycerides ≤ 2.5 x ULN. Note: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
• Life expectancy of at least 12 weeks
• Negative pregnancy test ≤ 72 hours before commencing study treatment (women of childbearing potential only).

You may not qualify if:

• Presence of KRAS mutation in tumour sample
• For Phase 1b group only, patients with prior pelvic radiotherapy.
• Systemic chemotherapy, immunotherapy, approved proteins/antibodies or any investigational agent within 4 weeks prior to commencing study treatment
• Radiotherapy within 14 days of commencing study treatment.
• Unresolved toxicities from prior systemic therapy or radiotherapy
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol
• Prior treatment with drugs targeting EGFR such as cetuximab, panitumumab or erlotinib
• Prior therapy with mTOR inhibitors (sirolimus, temsirolimus, everolimus)
• Prior therapy with irinotecan
• CYP3A4 enzyme inducing anti-convulsant medication ≤ 14 days prior to study treatment.
• Ketoconazole ≤ 7 days before study treatment.
• Uncontrolled diabetes mellitus defined by fasting glucose \>1.5 x ULN.
• Known cirrhosis, chronic active hepatitis, or chronic persistent hepatitis
• Patients with known interstitial lung disease or severely impaired lung function
• Patients with active bleeding diatheses.

Sponsors & Collaborators

• The Queen Elizabeth Hospital: lead
• Amgen: collaborator
• Novartis: collaborator

Study Sites (1)

The Queen Elizabeth Hospital

Adelaide, South Australia, 5011, Australia

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Panitumumab; Irinotecan; Everolimus

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; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Amanda Townsend, MBBS

  The Queen Elizabeth Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: May 28, 2010
• First Posted: June 8, 2010
• Study Start: June 1, 2010
• Primary Completion: August 1, 2015
• Study Completion: June 1, 2017
• Last Updated: November 6, 2017

Record last verified: 2017-11

Locations

AU (1)