Study of Trametinib and Ruxolitinib in Colorectal Cancer and Pancreatic Adenocarcinoma

NCT04303403 | Unknown Phase 1

• 1 other identifier: CTMT212XSG01T
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study to find out if the drug trametinib in combination with ruxolitinib is safe, tolerable and has beneficial effects in people who has certain type of cancers including the type that you have. Patients with RAS mutant colorectal cancer and pancreatic adenocarcinoma are invited to participate in this study. This is the first time that both trametinib and ruxolitinib are studied in combination. Trametinib is marketed in several countries with the brand name Mekinist® for the treatment of melanoma (a type of skin cancer). Trametinib has been studied extensively in cancer and has been tested in many patients. Ruxolitinib is an oral inhibitor of JAK1 and JAK2 tyrosine kinases and is approved for treatment of adult polycythemia vera and myelofibrosis. Ruxolitinib has been studied extensively in many patients.

Conditions

Colorectal Cancer; Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  Highest dose level at which less than one-third of the patients in the dose level experienced dose limiting toxicities (DLTs) during the first cycle of treatment

  28 days (1 cycle)

Secondary Outcomes (16)

• Frequency and severity of treatment-emergent Adverse Events and Serious Adverse Events

  From time of first study drug administration until 30 days after last dose of study drug

• Changes between baseline and post-baseline hematology laboratory parameters during treatment - Haemoglobin

  From time of first study drug administration until 30 days after last dose of study drug

• Changes between baseline and post-baseline hematology laboratory parameters during treatment - White blood count, Platelets, Absolute neutrophil count

  From time of first study drug administration until 30 days after last dose of study drug

• Changes between baseline and post-baseline hematology laboratory parameters during treatment - Neutrophils

  From time of first study drug administration until 30 days after last dose of study drug

• Changes between baseline and post-baseline biochemistry laboratory parameters during treatment - Urea, Sodium, Potassium, Chloride, Bicarbonate, Glucose, Magnesium, Calcium, Phosphate, Total cholesterol, High and low density lipoprotein, Triglycerides

  From time of first study drug administration until 30 days after last dose of study drug

Study Arms (1)

Dose Escalation and Expansion

EXPERIMENTAL

Dose Escalation: Trametinib 2mg daily monotherapy for 14 days. Followed by combination oral trametinb (2mg starting dose) daily and oral ruxolitinib (5mg starting dose) twice daily at assigned doses. Dose Expansion: Combination oral trametinb daily and oral ruxolitinib twice daily at the maximum tolerated dose (MTD) established at the Dose Escalation phase. A cycle of therapy will comprise of 28 days of combination trametinib and ruxolitinib treatment.

Drug: Trametinib; Drug: Ruxolitinib

Interventions

Trametinib DRUG

Taken orally once daily

Also known as: Mekinist

Dose Escalation and Expansion

Ruxolitinib DRUG

Taken orally twice daily

Also known as: Jakafi

Dose Escalation and Expansion

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients (male or female) ≥ 21.
• Patients with histological diagnosis of RAS mutant advanced colorectal and pancreatic adenocarcinoma having received at least 1 prior line of systemic therapy. Pancreatic cancer patients with KRAS mutation detected on plasma profiling having received at least 1 prior line of systemic therapy.
• Patients must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1.
• Life expectancy of at least 3 months.
• Written informed consent that is consistent with ICH-GCP guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2.
• Have adequate organ and hematologic function, as determined by:
• Absolute neutrophil count (ANC) ≥ 1,500/μl.
• Platelets ≥ 100,000/μl.
• Haemoglobin ≥ 9g/dL.
• Aspartate Amino Transferase (AST)/ Alanine Amino Transferase (ALT) ≤ 2.5 x upper limit of normal (ULN ≤ 5 x ULN is acceptable if liver metastases are present).
• Total bilirubin ≤1.5 x ULN (\< 3 ULN for patients with Gilbert syndrome).
• Creatinine clearance ≥ 60ml/min.
• Prothrombin time and activated partial thromboplastin time ≤ 1.5 x upper limit of normal (ULN) per institutional laboratory normal range.
• Ejection fraction ≥ 50% with no symptoms attributable to heart failure.

You may not qualify if:

• Received cytotoxic chemotherapy, investigational agents, or radiation within 14 days of study drug commencement, or 5 half-lives, whichever is shorter, and with recovery of clinically significant toxicities from that therapy.
• Received monoclonal antibodies or had surgery within 30 days of the first dose of study drug.
• Have been diagnosed with another primary malignancy within the past 3 years of study drug commencement (except for adequately treated non-melanoma skin cancer, cervical cancer in situ, or prostate cancer).
• Have CNS metastases that are symptomatic, neurologically unstable, or requiring an increasing dose of corticosteroids.
• Have meningeal involvement or spinal cord compression.
• Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
• Myocardial infarction (MI) within 6 months prior to the first dose.
• Unstable angina within 6 months prior to first dose.
• History of congestive heart failure (CHF).
• History of clinically significant atrial arrhythmia.
• Any history of ventricular arrhythmia.
• Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose.
• Have history or the presence of pulmonary interstitial disease or drug related pneumonitis.
• Have an ongoing or active infection.
• Patients with active HBV and HCV are excluded unless they are undergoing treatment for HBV and HCV.

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead

Study Sites (1)

National Cancer Centre

Singapore, 169610, Singapore

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

trametinib; ruxolitinib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• David Tai, MD

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Tai, MD

CONTACT

+65 6436 8000; david.tai.w.m@singhealth.com.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The first part of this study will be a standard 3+3 dose-escalating

Study Record Dates

• First Submitted: September 25, 2018
• First Posted: March 11, 2020
• Study Start: July 31, 2018
• Primary Completion: June 30, 2023
• Study Completion: March 31, 2024
• Last Updated: October 11, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)