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

November 2, 2017 updated by: Amanda Townsend, The Queen Elizabeth Hospital

A Phase IB/II Study of Second Line Therapy With Panitumumab, Irinotecan and Everolimus (PIE) in Metastatic Colorectal Cancer With KRAS WT

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
49

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • South Australia
      • Adelaide, South Australia, Australia, 5011
        • The Queen Elizabeth Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Panitumumab + Irinotecan + Everolimus
Drug: Panitumumab
Panitumumab 6mg/kg IV every 14 days
Other Names:
  • Vectibix
Drug: Irinotecan
Irinotecan 200mg/m2 IV every 14 days
Drug: Everolimus
Everolimus daily po (dosage varies with cohort)
Other Names:
  • RAD001

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
at end of cycle 2 (each cycle is 14 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Approximately 24 weeks
Response rate
Time Frame: Assessed every 6 weeks until disease progression
Objective tumour response as per RECIST criteria V1.0
Assessed every 6 weeks until disease progression
Progression free survival
Time Frame: Until disease progression, occurrence of new disease or death
Until disease progression, occurrence of new disease or death
Overall Survival
Time Frame: Assessed 3 monthly until death
Assessed 3 monthly until death

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The Queen Elizabeth Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Novartis
Amgen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Amanda Townsend, MBBS, The Queen Elizabeth Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 28, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 7, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 8, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 6, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 2, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AU-2009-0003/CRAD001CAU06T

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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