Clinical trial NCT01139138: Safety Study of the Combination of Panitumumab, Irinotecan and Everolimus in the Treatment of Advanced Colorectal Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Colorectal Carcinoma
Colorectal Tumors
Neoplasms, Colorectal
Keywords: Colorectal Cancer
Colorectal Carcinoma
Colorectal Tumors
Neoplasms, Colorectal
Lead sponsor: The Queen Elizabeth Hospital
Sponsor class: OTHER
Collaborators: name: Amgen
name: Novartis
First posted: 2010-06-08
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Eligibility criteria: 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.

Primary outcomes:
measure: Dose limiting toxicities
timeFrame: at end of cycle 2 (each cycle is 14 days)
Secondary outcomes:
measure: Safety & toxicity
timeFrame: Approximately 24 weeks
measure: Response rate
timeFrame: Assessed every 6 weeks until disease progression
measure: Progression free survival
timeFrame: Until disease progression, occurrence of new disease or death
measure: Overall Survival
timeFrame: Assessed 3 monthly until death
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
Study officials:
affiliation: The Queen Elizabeth Hospital
name: Amanda Townsend, MBBS
role: PRINCIPAL_INVESTIGATOR
References: