EVICT: This phase I/II trial is combining BRAF and EGFR inhibitiors in the treatment of BRAF V600E colorectal cancer, and advanced or metastatic lung cancerA Phase I/II Trial of the combination of BRAF and EGFR inhibition in BRAF V600E mutant colorectal, advanced or metastatic lung adenocarcinoma and other cancers.

Inclusion

1. Male or female patients greater than or equal to 18 years of age at the time of study entry
2. All patients must have histological or cytological confirmed metastatic colorectal cancer with a BRAF V600E mutation of their primary cancer or related metastases. Patients with other tumour types with a proven BRAF V600E mutation can be considered for enrolment into the Expansion Phase exploratory cohort with the permission of the Study Chair.
3. Patients with BRAF V600E mCRC are permitted to have had a maximum of 2-lines of therapy for metastatic disease. A maintenance strategy post 1st-line treatment is not considered as an additional line of therapy, nor is rechallenge with oxaliplatin. Patients with lung adenocarcinoma are required to have received prior treatment with a platinum doublet. There is no requirement for previous treatment for other tumour types.
4. All patients must have measurable disease per RECIST 1.1 criteria.
5. A tumour paraffin tissue block or 20 - 30 unstained slides from the tumour tissue block must be available for the purpose of biomarker analyses. Obtaining archived tumour material or unstained slides from an archived tumour block will suffice to meet this requirement. The availability of the tumour tissue block must be confirmed at screening for a patient to be considered eligible. If no tissue block and fewer than 20 unstained slides are available, eligibility must be confirmed with the Study Chair or delegate.
6. ECOG performance status 0 to 1 inclusive.
7. Participants must have adequate organ and marrow function as defined below:
a) Absolute neutrophil count greater than or equal to 1.5 x 109/L
b) Platelets greater than or equal to 100 x 109/L
c) ALT and AST less than or equal to 2.5 x upper limit of normal (ULN), or less than or equal to 5 x ULN if liver metastases are present
d) Total serum bilirubin less than or equal to 1.5 x ULN
e) Serum creatinine less than or equal to 1.5 x ULN, or creatinine clearance > 50ml/min
8. Participants must be suitable for oral drug administration.
9. Life expectancy > 3 months.
10. Female patients of childbearing potential (see below) must:
a) Be on highly effective contraception. Highly effective contraception methods include:
* total abstinence, or
* sterilisation (see below), or
* combination of any two of the following (a+b, or a+c, or b+c):
* Use of oral, injected or implanted hormonal methods of contraception. Hormonal contraceptives include any marketed contraceptive agent that includes an oestrogen and/or a progestin.
* Placement of an intrauterine device (IUD)
* Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/cream/ vaginal suppository
b) Have a negative serum or urine pregnancy test performed within the 7 days before start of treatment.
c) Highly effective contraception for females of child bearing potential must be maintained throughout the study and for 6 months after study drug discontinuation.
11. Female patients not of child-bearing potential. Women are considered not of child bearing potential if they have had either:
a) 12 months of natural (spontaneous) amenorrhoea with an appropriate clinical profile (eg. age appropriate, history of vasomotor symptoms), or
b) A surgical bilateral oophorectomy (with or without hysterectomy), or
c) Tubal ligation at least 6 weeks ago.
In the case of unilateral oophorectomy alone, a woman is considered not of child-bearing potential only once the reproductive status has been confirmed by follow up hormone level assessment.
12. Sexually active males must use a condom during intercourse while taking the drug and for 6 months after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomised men in order to prevent delivery of the drug via seminal fluid.
13. Absence of any psychological, familial or sociological condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before trial entry.
14. Ability to understand and the willingness to sign a written informed consent. Before study entry, written informed consent must be obtained from patient prior to performing any study-related procedures.