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

NCT ID: NCT01139138

Last Updated: 2017-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

49 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-06-30

Study Completion Date

2017-06-30

Brief Summary

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

Detailed Description

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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

Conditions

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Colorectal Cancer Colorectal Carcinoma Colorectal Tumors Neoplasms, Colorectal

Keywords

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Colorectal Cancer Colorectal Carcinoma Colorectal Tumors Neoplasms, Colorectal

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Panitumumab + Irinotecan + Everolimus

Group Type EXPERIMENTAL

Panitumumab

Intervention Type DRUG

Panitumumab 6mg/kg IV every 14 days

Irinotecan

Intervention Type DRUG

Irinotecan 200mg/m2 IV every 14 days

Everolimus

Intervention Type DRUG

Everolimus daily po (dosage varies with cohort)

Interventions

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Panitumumab

Panitumumab 6mg/kg IV every 14 days

Intervention Type DRUG

Irinotecan

Irinotecan 200mg/m2 IV every 14 days

Intervention Type DRUG

Everolimus

Everolimus daily po (dosage varies with cohort)

Intervention Type DRUG

Other Intervention Names

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Vectibix RAD001

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role collaborator

Novartis

INDUSTRY

Sponsor Role collaborator

The Queen Elizabeth Hospital

OTHER

Sponsor Role lead

Responsible Party

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Amanda Townsend

Dr

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Amanda Townsend, MBBS

Role: PRINCIPAL_INVESTIGATOR

The Queen Elizabeth Hospital

Locations

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The Queen Elizabeth Hospital

Adelaide, South Australia, Australia

Site Status

Countries

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Australia

Other Identifiers

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AU-2009-0003/CRAD001CAU06T

Identifier Type: -

Identifier Source: org_study_id