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Trial record 1 of 1 for:    ctmt212xsg01t
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Study of Trametinib and Ruxolitinib in Colorectal Cancer and Pancreatic Adenocarcinoma

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ClinicalTrials.gov Identifier: NCT04303403
Recruitment Status : Recruiting
First Posted : March 11, 2020
Last Update Posted : March 11, 2020
Sponsor:
Information provided by (Responsible Party):
National Cancer Centre, Singapore

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Pancreatic Adenocarcinoma Drug: Trametinib Drug: Ruxolitinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Sequential Assignment
Intervention Model Description: The first part of this study will be a standard 3+3 dose-escalating
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib Study Evaluating Safety and Tolerability of Combination Trametinib and Ruxolitinib in Patients With Advanced RAS Mutant Colorectal Cancer and Pancreatic Adenocarcinoma
Actual Study Start Date : July 31, 2018
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose Escalation and Expansion

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:

Trametinib 2mg daily monotherapy for 14 days. Followed by 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
Taken orally once daily
Other Name: Mekinist

Drug: Ruxolitinib
Taken orally twice daily
Other Name: Jakafi




Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: 28 days (1 cycle) ]
    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


Secondary Outcome Measures :
  1. Frequency and severity of treatment-emergent Adverse Events and Serious Adverse Events [ Time Frame: From time of first study drug administration until 30 days after last dose of study drug ]
    To assess the safety of the drug combination. During the dose escalation phase, this includes the incidences of dose limiting toxicities during the first 2 cycles of treatment.

  2. Changes between baseline and post-baseline hematology laboratory parameters during treatment - Haemoglobin [ Time Frame: From time of first study drug administration until 30 days after last dose of study drug ]
    Unit of measure: g/dL. To assess the safety of the drug combination

  3. Changes between baseline and post-baseline hematology laboratory parameters during treatment - White blood count, Platelets, Absolute neutrophil count [ Time Frame: From time of first study drug administration until 30 days after last dose of study drug ]
    Unit of measure: x 10^9/L. To assess the safety of the drug combination.

  4. Changes between baseline and post-baseline hematology laboratory parameters during treatment - Neutrophils [ Time Frame: From time of first study drug administration until 30 days after last dose of study drug ]
    Unit of measure: Percentage component of white blood cells. To assess the safety of the drug combination.

  5. 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 [ Time Frame: From time of first study drug administration until 30 days after last dose of study drug ]
    Unit of measure: mmol/L. To assess the safety of the drug combination

  6. Changes between baseline and post-baseline biochemistry laboratory parameters during treatment - Uric acid, Creatinine, Total bilirubin [ Time Frame: From time of first study drug administration until 30 days after last dose of study drug ]
    Unit of measure: umol/L. To assess the safety of the drug combination

  7. Changes between baseline and post-baseline biochemistry laboratory parameters during treatment - Total protein, Albumin [ Time Frame: From time of first study drug administration until 30 days after last dose of study drug ]
    Unit of measure: g/L. To assess the safety of the drug combination

  8. Changes between baseline and post-baseline biochemistry laboratory parameters during treatment - Alkaline phosphatase, Alanine transaminase, Aspartate transaminase, Lactate dehydrogenase, Beta-human chorionic gonadotrophin [ Time Frame: From time of first study drug administration until 30 days after last dose of study drug ]
    Unit of measure: U/L. To assess the safety of the drug combination

  9. Frequency of dose interruptions [ Time Frame: From time of first study drug administration until 30 days after last dose of study drug ]
    To assess the tolerability of the drug combination.

  10. Frequency of dose reductions [ Time Frame: From time of first study drug administration until 30 days after last dose of study drug ]
    To assess the tolerability of the drug combination

  11. Pharmacokinetics (PK): Trough concentrations of trametinb [ Time Frame: From cycle 1-6 of study (each cycle is 28 days) ]
    Trough concentrations of trametinb at different cycles of combination treatment with ruxolitinib

  12. Tumour Markers: CEA and CA 19-9 in blood samples [ Time Frame: From cycle 1 up to last cycle of treatment (each cycle is 28 days) ]
    Changes from baseline tumour markers (CEA and CA 19-9) in blood samples

  13. Overall Response Rate [ Time Frame: From time of first study drug administration until first occurrence of disease progression, up to 2 years ]
    The best overall response is the best response recorded from the start of the treatment until disease progression (PD)/ recurrence (taking as reference for PD the smallest measurements recorded since the treatment started).

  14. Disease Control Rate [ Time Frame: From time of first study drug administration until best overall response, first occurence of disease progression, up to 2 years ]
    Percentage of patients who have achieved complete response, partial response and stable disease in accordance to RECIST 1.1.

  15. Progression Free Survival [ Time Frame: From time of first study drug administration until first occurence of disease progression, or death from any cause, up to 2 years ]
    Time elapsed between treatment initiation and tumour progression or death from any cause, with censoring of patients who are lost to follow-up.

  16. Overall Survival [ Time Frame: From time of first study drug administration to death from any cause, up to 2 years ]
    Time elapsed between treatment initiation and death from any cause, with censoring of patients who are lost to follow-up.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients (male or female) ≥ 21.
  • Patients with histological diagnosis of RAS mutant advanced colon 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.
  • Have normal QT interval on screening electrocardiogram (ECG) evaluation, defined as QT interval corrected (Fridericia) (QTcF) of ≤450 ms in males or ≤470 ms in females.
  • For female patients of childbearing potential, a negative pregnancy test must be documented prior to enrolment.
  • Female and male patients who are fertile must agree to use a highly effective form of contraception with their sexual partners throughout study participation.
  • Have the willingness and ability to comply with scheduled visits and study procedures.

Exclusion Criteria:

  • 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.
  • Have a history of or active significant gastrointestinal (GI) bleeding within 3 months of the first dose.
  • Patients who are on immunosuppressive therapy.
  • Patients who have retinal vein occlusion and retinal pigment epithelial detachment.
  • On medications which are potent and moderate inhibitor and inducers of CYP3A4.
  • Patients with moderate to severe hepatic impairment (Child Pugh B and C).
  • Patients with history of severe allergic skin reactions or current skin conditions.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04303403


Contacts
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Contact: David Tai, MD +65 6436 8000 david.tai.w.m@singhealth.com.sg
Contact: Stella Chan stella.chan.l.l@nccs.com.sg

Locations
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Singapore
National Cancer Centre Recruiting
Singapore, Singapore, 169610
Sponsors and Collaborators
National Cancer Centre, Singapore
Investigators
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Principal Investigator: David Tai, MD National Cancer Centre, Singapore
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Responsible Party: National Cancer Centre, Singapore
ClinicalTrials.gov Identifier: NCT04303403    
Other Study ID Numbers: CTMT212XSG01T
First Posted: March 11, 2020    Key Record Dates
Last Update Posted: March 11, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Adenocarcinoma
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Trametinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action