Colorectal CancerPhase 1NCT04303403
Study of Trametinib and Ruxolitinib in Colorectal Cancer and Pancreatic Adenocarcinoma
A Phase 1 study testing Trametinib and Ruxolitinib in people with Colorectal Cancer and Pancreatic Adenocarcinoma, run by National Cancer Centre, Singapore at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Colorectal Cancer, Pancreatic Adenocarcinoma
- What is being tested?
- Trametinib and Ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteSingapore
- Study dates
- 31 Jul 2018to 31 Mar 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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:
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- 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.
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
National Cancer Centre
Singapore, 169610
About this study
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
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
- Being tested
- Trametinib, Ruxolitinib
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrametinibDrug
Also called Mekinist
Taken orally once daily
RuxolitinibDrug
Also called Jakafi
Taken orally twice daily
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Trametinib; Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 28 days (1 cycle)
Secondary outcomes (16)
Frequency and severity of treatment-emergent Adverse Events and Serious Adverse Events
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.
Measured: 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
Unit of measure: g/dL. To assess the safety of the drug combination
Measured: 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
Unit of measure: x 10^9/L. To assess the safety of the drug combination.
Measured: 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
Unit of measure: Percentage component of white blood cells. To assess the safety of the drug combination.
Measured: 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
Unit of measure: mmol/L. To assess the safety of the drug combination
Measured: 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 - Uric acid, Creatinine, Total bilirubin
Unit of measure: umol/L. To assess the safety of the drug combination
Measured: 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 - Total protein, Albumin
Unit of measure: g/L. To assess the safety of the drug combination
Measured: 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 - Alkaline phosphatase, Alanine transaminase, Aspartate transaminase, Lactate dehydrogenase, Beta-human chorionic gonadotrophin
Unit of measure: U/L. To assess the safety of the drug combination
Measured: From time of first study drug administration until 30 days after last dose of study drug
Frequency of dose interruptions
To assess the tolerability of the drug combination.
Measured: From time of first study drug administration until 30 days after last dose of study drug
Frequency of dose reductions
To assess the tolerability of the drug combination
Measured: From time of first study drug administration until 30 days after last dose of study drug
Pharmacokinetics (PK): Trough concentrations of trametinb
Trough concentrations of trametinb at different cycles of combination treatment with ruxolitinib
Measured: From cycle 1-6 of study (each cycle is 28 days)
Tumour Markers: CEA and CA 19-9 in blood samples
Changes from baseline tumour markers (CEA and CA 19-9) in blood samples
Measured: From cycle 1 up to last cycle of treatment (each cycle is 28 days)
Overall Response Rate
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).
Measured: From time of first study drug administration until first occurrence of disease progression, up to 2 years
Disease Control Rate
Percentage of patients who have achieved complete response, partial response and stable disease in accordance to RECIST 1.1.
Measured: From time of first study drug administration until best overall response, first occurence of disease progression, up to 2 years
Progression Free Survival
Time elapsed between treatment initiation and tumour progression or death from any cause, with censoring of patients who are lost to follow-up.
Measured: From time of first study drug administration until first occurence of disease progression, or death from any cause, up to 2 years
Overall Survival
Time elapsed between treatment initiation and death from any cause, with censoring of patients who are lost to follow-up.
Measured: From time of first study drug administration to death from any cause, up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2020
- Study start31 Jul 2018
- Primary completion30 Jun 2023
- Study completion31 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- The first part of this study will be a standard 3+3 dose-escalating
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Centre, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Tai, MD, Principal investigator, National Cancer Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04303403
- Sponsor's protocol ID
- CTMT212XSG01T
- Status last verified
- Oct 2023
- First submitted
- 25 Sep 2018
- Last updated
- 11 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04303403
- Acronym / sponsor ID
- CTMT212XSG01T
- Conditions
- Colorectal Cancer, Pancreatic Adenocarcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- National Cancer Centre, SingaporeUniversity, hospital or other
- Study start
- 31 Jul 2018 (actual)
- Primary completion
- 30 Jun 2023 (actual)
- Study completion
- 31 Mar 2024 (estimated)
- First posted
- 11 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The first part of this study will be a standard 3+3 dose-escalating
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation and Expansion | Experimental | Drug: Trametinib, Drug: RuxolitinibDose 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. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrametinibAlso: MekinistTaken orally once daily | Drug | Dose Escalation and Expansion |
| RuxolitinibAlso: JakafiTaken orally twice daily | Drug | Dose Escalation and Expansion |
Primary outcome
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
16 secondary outcomes
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
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
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
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
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
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
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
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
Frequency of dose interruptions
Time frame: From time of first study drug administration until 30 days after last dose of study drug
Frequency of dose reductions
Time frame: From time of first study drug administration until 30 days after last dose of study drug
Pharmacokinetics (PK): Trough concentrations of trametinb
Time frame: From cycle 1-6 of study (each cycle is 28 days)
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)
Overall Response Rate
Time frame: From time of first study drug administration until first occurrence of disease progression, up to 2 years
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
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
Overall Survival
Time frame: From time of first study drug administration to death from any cause, up to 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Tai, MD principal investigator
National Cancer Centre, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Trametinib and Ruxolitinib in people with Colorectal Cancer and Pancreatic Adenocarcinoma, run by National Cancer Centre, Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact David Tai, MD (+65 6436 8000, david.tai.w.m@singhealth.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (time frame: 28 days (1 cycle)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2023.