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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01139138
Recruitment Status : Completed
First Posted : June 8, 2010
Last Update Posted : November 6, 2017
Information provided by (Responsible Party):
Amanda Townsend, The Queen Elizabeth Hospital

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

Condition or disease Intervention/treatment Phase
Colorectal Cancer Colorectal Carcinoma Colorectal Tumors Neoplasms, Colorectal Drug: Panitumumab Drug: Irinotecan Drug: Everolimus Phase 1 Phase 2

Detailed Description:
This is an open label uncontrolled phase IB/II study to determine the maximum tolerated dose (MTD) and assess the efficacy of everolimus, irinotecan and panitumumab when given in combination for patients with metastatic colorectal cancer and KRAS wild-type (WT). Patients with metastatic colorectal cancer (mCRC) that have failed fluorouracil based first line therapy will be included. It is anticipated that approximately 50 patients will be enrolled over a period of 24 months

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IB/II Study of Second Line Therapy With Panitumumab, Irinotecan and Everolimus (PIE) in Metastatic Colorectal Cancer With KRAS WT
Study Start Date : June 2010
Actual Primary Completion Date : August 2015
Actual Study Completion Date : June 2017

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Panitumumab + Irinotecan + Everolimus Drug: Panitumumab
Panitumumab 6mg/kg IV every 14 days
Other Name: Vectibix

Drug: Irinotecan
Irinotecan 200mg/m2 IV every 14 days

Drug: Everolimus
Everolimus daily po (dosage varies with cohort)
Other Name: RAD001

Primary Outcome Measures :
  1. Dose limiting toxicities [ Time Frame: at end of cycle 2 (each cycle is 14 days) ]
    To determine the maximum tolerated dose (MTD)of everolimus, irinotecan and panitumumab when given in combination for patients with Kras WT mCRC

Secondary Outcome Measures :
  1. Safety & toxicity [ Time Frame: Approximately 24 weeks ]
    Safety and toxicity assessed weekly during the phase Ib component (as per NCI CTCAE version 3.0) and fortnightly during the phase II component

  2. Response rate [ Time Frame: Assessed every 6 weeks until disease progression ]
    Objective tumour response as per RECIST criteria V1.0

  3. Progression free survival [ Time Frame: Until disease progression, occurrence of new disease or death ]
  4. Overall Survival [ Time Frame: Assessed 3 monthly until death ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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).
  • Written informed consent including consent for biomarker studies

Exclusion Criteria:

  • 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.
  • Any uncontrolled clinically significant cardiac disease, arrhythmias or angina pectoris
  • Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea
  • Chronic treatment with immunosuppressives
  • Patients with a known history of HIV seropositivity
  • Patients who have any severe and/or uncontrolled medical conditions or infections
  • Untreated or symptomatic CNS metastases
  • Patients who have a history of another primary malignant disease
  • Pregnancy or lactation.
  • Women and partners of women of childbearing potential who are not using effective contraception.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01139138

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Australia, South Australia
The Queen Elizabeth Hospital
Adelaide, South Australia, Australia, 5011
Sponsors and Collaborators
The Queen Elizabeth Hospital
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Principal Investigator: Amanda Townsend, MBBS Queen Elizabeth Hospital
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Responsible Party: Amanda Townsend, Dr, The Queen Elizabeth Hospital Identifier: NCT01139138    
Other Study ID Numbers: AU-2009-0003/CRAD001CAU06T
First Posted: June 8, 2010    Key Record Dates
Last Update Posted: November 6, 2017
Last Verified: November 2017
Keywords provided by Amanda Townsend, The Queen Elizabeth Hospital:
Colorectal Cancer
Colorectal Carcinoma
Colorectal Tumors
Neoplasms, Colorectal
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological