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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01139138




Registration number
NCT01139138
Ethics application status
Date submitted
28/05/2010
Date registered
8/06/2010
Date last updated
6/11/2017

Titles & IDs
Public title
Safety Study of the Combination of Panitumumab, Irinotecan and Everolimus in the Treatment of Advanced Colorectal Cancer
Scientific title
A Phase IB/II Study of Second Line Therapy With Panitumumab, Irinotecan and Everolimus (PIE) in Metastatic Colorectal Cancer With KRAS WT
Secondary ID [1] 0 0
AU-2009-0003/CRAD001CAU06T
Universal Trial Number (UTN)
Trial acronym
PIE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 0 0
Colorectal Carcinoma 0 0
Colorectal Tumors 0 0
Neoplasms, Colorectal 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Panitumumab
Treatment: Drugs - Irinotecan
Treatment: Drugs - Everolimus

Experimental: Panitumumab + Irinotecan + Everolimus -


Treatment: Drugs: Panitumumab
Panitumumab 6mg/kg IV every 14 days

Treatment: Drugs: Irinotecan
Irinotecan 200mg/m2 IV every 14 days

Treatment: Drugs: Everolimus
Everolimus daily po (dosage varies with cohort)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose limiting toxicities
Timepoint [1] 0 0
at end of cycle 2 (each cycle is 14 days)
Secondary outcome [1] 0 0
Safety & toxicity
Timepoint [1] 0 0
Approximately 24 weeks
Secondary outcome [2] 0 0
Response rate
Timepoint [2] 0 0
Assessed every 6 weeks until disease progression
Secondary outcome [3] 0 0
Progression free survival
Timepoint [3] 0 0
Until disease progression, occurrence of new disease or death
Secondary outcome [4] 0 0
Overall Survival
Timepoint [4] 0 0
Assessed 3 monthly until death

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2017
Sample size
Target
Accrual to date
Final
49
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
The Queen Elizabeth Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
5011 - Adelaide

Funding & Sponsors
Primary sponsor type
Other
Name
The Queen Elizabeth Hospital
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Amgen
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Novartis
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will assess the safety of panitumumab, irinotecan and everolimus when given in
combination to treat advanced colorectal cancer
Trial website
https://clinicaltrials.gov/ct2/show/NCT01139138
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Amanda Townsend, MBBS
Address 0 0
The Queen Elizabeth Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01139138