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Clinical Trial Details

An open label dose-finding, safety and tolerability study of Panitumumab, Irinotecan, Trifluridine/Tipiracil in RAS wild-type patients with metastatic colorectal cancer.

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Trial Information

Broad Health Condition Cancer

Specific Health ConditionBowel - Back passage (rectum) or large bowel (colon)

Trial FocusTreatment

Recruitment statusRecruiting

Recruitment Details
Recruitment State

The Queen Elizabeth Hospital - Woodville
Flinders Medical Centre - Bedford Park
The Royal Adelaide Hospital - Adelaide
Royal Brisbane & Womens Hospital - Herston

5011 - Woodville
5042 - Bedford Park
5000 - Adelaide

Anticipated date of first participant enrolment31/07/2018

Anticipated date of last participant enrolment31/07/2018

Phase of TrialPhase 1 / Phase 2

Has the study received ethics approval?Further information iconApproved

Trial summary

This study aims to determine the maximum tolerated dose (MTD) and assess the efficacy of panitumumab, irinotecan and trifluridine/tipiracil when given in combination for participants with RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC).

Who is it for?
You may be eligible to join this study if you are aged 18 years or above and have a confirmed diagnosis of metastatic colorectal cancer that is RAS/BRAF wild type.

Study details
This study will be conducted in two parts: phase Ib and phase II. The study will commence with a phase Ib dose escalation phase, during which participants will be administered Irinotecan (180mg/m2) and Panitumumab (6mg/Kg) intravenously (IV) on Day 1 of every 14 day cycle, in combination with oral Trifluridine/tipiracil twice a day on Days 1-5 of every 14 day cycle. Dosing of trifluridine/Tipiracil will commence at 25 mg/m2 orally twice a day in the first group. If tolerated, the dose will be elevated for subsequent groups up to a maximum of 35 mg/m2 orally twice a day. Phase II of the study will enrol a separate group of participants who will receive the maximum tolerated dose determined in phase Ib. Treatment in both phases will continue until disease progression, unacceptable toxicity or participant withdrawal.

Participants will be regularly assessed throughout the study in order to monitor safety and tumour response. Follow-up visits will occur every 12 weeks after the end of treatment visit until death or study closure.

It is hoped that this study will provide evidence for further research into this combination, and improve health outcomes for patients with this disease.

Key inclusion criteria

Inclusion criteria
•	Provide a signed and dated Participant Information and Consent Sheet
•	Age greater than or equal to 18 years
•	Histological diagnosis of colorectal cancer that is RAS/BRAF wild type.
•	Metastatic disease not amenable to resection, including borderline resectable cases.
•	Measurable disease as assessed by CT scan in accordance with RECIST v1.1 criteria.
•	Phase Ib group only: Received and failed one, and only one, prior chemotherapy regimen for mCRC consisting of first-line fluoropyrimidine-based chemotherapy (Treatment failure is defined as radiological progression per RECIST v1.1 criteria after therapy for metastatic disease, prior adjuvant therapy completed <6 months prior to metastatic disease, or toxicity limiting further therapy). 
Phase II group only: previously untreated mCRC.
•	Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 during screening..
•	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 greater than or equal to 1.25 x upper limit of normal (ULN) range and ALT or AST greater than or equal to 2.5xULN (or greater than or equal to 5xULN if liver metastases present) within 7 days of enrolment
•	Magnesium greater than or equal to lower limit of normal within 7 days of enrolment.
•	Life expectancy of at least 12 weeks.
•	Negative pregnancy test within 7 days before commencing study treatment (women of childbearing potential only).

Minimum age18 Years

GenderBoth males and females

Can Healthy volunteers participate?No

Key exclusion criteria

Exclusion criteria
•	Phase  Ib group only: any history of prior pelvic radiotherapy
•	Phase Ib group only: history of prior 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 greater than or equal to grade 2 resulting from prior systemic therapy or radiotherapy.
•	Any medical or psychiatric conditions that compromise the patient’s ability to give informed consent or to complete the protocol.
•	Prior treatment with EGFR targeting therapies such as cetuximab, panitumumab or erlotinib.
•	Prior therapy with irinotecan.
•	History of interstitial pneumonitis, pulmonary fibrosis or evidence of interstitial pneumonitis, or pulmonary fibrosis on baseline chest CT scan.
•	History of Gilbert syndrome.
•	Known cirrhosis, chronic active hepatitis, or chronic persistent hepatitis.
•	Patients with active bleeding diathesis.
•	Any uncontrolled clinically significant cardiac disease, arrhythmias or angina pectoris
•	Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea (defined as Common Terminology Criteria for Adverse Events (CTCAE) greater than or equal to grade 2 [version 4.03])
•	Chronic treatment with immunosuppressives.
•	Patients with a known history of HIV seropositivity.
•	Patients who have any severe and/or uncontrolled medical conditions or infections
•	Patients who have a history of another primary malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer treated with curative intent >2 years previously without evidence of relapse.
•	Known brain metastasis.
•	Pregnancy or lactation.
•	Women and partners of women of childbearing potential who are not using effective contraception. Highly effective contraception must be used throughout study treatment and for 6 months following the completion of all study treatment.
•	Patients with history of serious drug adverse reactions.
Contact details and further information

Sponsor Primary Sponsor Type: Hospital
Primary Sponsor Name: Central Adelaide Local Health Network Incorporated
Primary Sponsor Address: Level 3, Margaret Graham Building Royal Adelaide Hospital, North Terrace, Adelaide South Australia, 5000
Primary Sponsor Country: Australia

Trial IDACTRN12617001190392


Contact person for information and recruitmentMs
Jerneen Williams
The Queen Elizabeth Hospital Haematology and Oncology 28 Woodville Road Woodville South South Australia 5011
+61 8 8222 6410
+61 8 8222 7486
Further information