A study of a new combination of drugs (cetuximab, cobimetinib and palbociclib) in subjects with advanced or metastatic colorectal cancer who have failed all available standard therapies

Phase 1

• Conditions: Colorectal Cancer; Cancer - Bowel - Back passage (rectum) or large bowel (colon)

• Registration Number: ACTRN12621001436864
• Lead Sponsor: Cothera Bioscience Pty ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-10-25
• Study Completion: 2022-07-27
• Last Update Posted: 29 August 2022

Recruitment & Eligibility

• Status: Stopped early
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

* Males or females aged 18 years and older.
* Signed informed consent. 
* Histologically or cytologically confirmed advanced or metastatic colorectal cancer that is refactory to all available standard therapies
* Tumor expression of BRAF V600E mutation or KRAS mutation
* Females postmenopausal or willing to use effective birth control
* Males patients must use effective birth control
* Females with a negative pregnancy test at Screening 
* Have stopped previous anticancer therapy for at least 3 weeks or 5 half lives prior to Screening

Exclusion Criteria

* Concomitant anticancer therapy, systemic immune therapy, hormonal therapy, nontraditional and/or herbal therapy as cancer therapy.
* Unresolved NCI CTCAE (v5.0) greater than or equal to Grade 2 toxicity from any prior anticancer therapy
* Symptomatic brain metastases
* History of known spinal cord cell compression or carcinomatous meningitis
* Pregnant or actively breastfeeding.
* Active hepatitis B or hepatitis C infection
* Known history of HIV infection
* Documented malignancies other than CRC within 3 years prior
* Clinically significant cardiac disease
* Signs or symptoms of organ failure, major chronic illnesses other than cancer
* Treatment with medications known to be strong CYP3A4 inhibitors within 7 days prior to Day 1 of treatment or CYP3A4 inducers within 14 days prior to Day 1 of treatment.
* Previous history of keratitis, ulcerative keratitis or severe form of dry eye
* Known pre-existing interstitial lung disease
* History of or evidence of retinal pathology
* Treatment with another investigational drug, or investigational device within 30 days before dosing

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Phase 1: Determination of Dose Limiting Toxicity (DLT). A DLT will be defined using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v 5.0<br><br>[Phase 1 DLTs will be assessed during the first cycle of treatment (28 days) and are events that are considered possiby related to the study drug combination for each cohort. After the treatment of each cohort, data will be reviewed to assess patient status and study drug related toxicities from the current cohort before deciding the escalation plan and dose level for the next cohort.<br><br>];Phase 2: Determination of Objective Response Rate as determined by MRI scanning with RECIST criteria reporting[Phase 2: patients will be reviewed for objective response rate after at least 2 treatment cycles]

Secondary Outcome Measures

Name	Time	Method
To assess pharmacokinetics of the study drug triplet combination during Phase 1 portion of study. Parameters to be assessed will include maximum concentration (Cmax), time of maximum observed concentration (Tmax) and steady state concentration measured before the next dose of study drug (C trough)[PK blood draws will occur on Day 1 and Day 22 of Cycle 1 and Day 1 of Cycle 2. PK will be drawn pre dose and 1, 2, 4 and 6 hours post dose after the IV infusion of cetuximab.]