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Metastatic Colon CarcinomaPhase 1NCT03317119

Trametinib and Trifluridine and Tipiracil Hydrochloride in Treating Patients With Colon or Rectal Cancer That is Advanced, Metastatic, or Cannot Be Removed by Surgery

A Phase 1 study testing Laboratory Biomarker Analysis, Trametinib and Trifluridine and Tipiracil Hydrochloride in people with Metastatic Colon Carcinoma and Metastatic Colorectal Carcinoma, run by City of Hope Medical Center at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of trametinib and trifluridine and tipiracil hydrochloride in treating patients with colon or rectal cancer that has spread to other places in the body (advanced/metastatic) or cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Trametinib and Trifluridine and Tipiracil Hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
8 sitesUnited States
Study dates
11 Apr 2018to 14 Jul 2023
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • All subjects must have the ability to understand and the willingness to sign a written informed consent
  • All patients must be able to take oral medications
  • All patients must be deemed by investigator to have the initiative and means to be compliant with the study protocol (treatment and follow-up)
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Pathologically confirmed advanced, unresectable, or metastatic colon or rectal cancer who have had intolerance to or progression after a fluoropyrimidine, oxaliplatin, irinotecan, and cetuximab or panitumumab in the event of wild-type RAS/BRAF tumors
  • Of note, prior bevacizumab or regorafenib exposure is not mandated as some patients are deemed poor candidates for anti-angiogenesis therapy and never receive these agents
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  • Tumors must have undergone expanded molecular profiling with a Clinical Laboratory Improvement Act (CLIA)-certified platform that evaluates, at a minimum, RAS, PIK3CA, PTEN and BRAF mutations status
  • Documented RAS-mutated tumor without activating PIK3CA mutations or PTEN mutation (loss of PTEN or silencing)
  • Measurable disease by RECIST 1.1 guidelines
  • Last chemotherapy at least 3 weeks from initiation of study treatment
  • No investigational agents within 4 weeks from initiation of study treatment
  • Negative serum or urine beta-human chorionic gonadotropin (HcG) test (female patient of childbearing potential only) performed within 72 hours of prior to first study dose
  • Absolute neutrophil count (ANC) >= 1500/mm^3 (to be performed within 28 days prior to day 1 of protocol therapy)
  • NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
  • Platelets >= 75,000/mm^3 without transfusions (to be performed within 28 days prior to day 1 of protocol therapy)
  • Hemoglobin (Hgb) >= 8 g/dL without transfusions (to be performed within 28 days prior to day 1 of protocol therapy)
  • Total serum bilirubin < upper limit of normal (ULN) (to be performed within 28 days prior to day 1 of protocol therapy)
  • Aspartate aminotransferase (AST) =< 2.5 x ULN if no liver metastases or =< 5 x ULN if liver metastases (to be performed within 28 days prior to day 1 of protocol therapy)
  • Alanine aminotransferase (ALT) =< 2.5 x ULN if no liver metastases or =< 5 x ULN if liver metastases (to be performed within 28 days prior to day 1 of protocol therapy)
  • Creatinine < 1.5 x ULN or creatinine clearance of >= 60 mL/min per the Cockcroft-Gault formula (to be performed within 28 days prior to day 1 of protocol therapy)
  • Female of childbearing potential: negative urine or serum pregnancy test (to be performed within 28 days prior to day 1 of protocol therapy)
  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Corrected QT (QTc) interval =< 480 ms (12 lead-electrocardiography [ECG]) (to be performed within 28 days prior to day 1 of protocol therapy)
  • Left ventricular ejection fraction >= 50% as determined by multigated acquisition (MUGA) scan or echocardiogram (to be performed within 28 days prior to day 1 of protocol therapy)
  • Normal eye examination (to be performed within 28 days prior to day 1 of protocol therapy)
  • Women of childbearing potential must use highly effective methods of contraception throughout the study and for 4 months after study drug discontinuation
  • Sexually active men must use a condom during intercourse while taking study drug and for 60 days after study drug discontinuation; a condom is required for vasectomized men to prevent delivery of study drug via seminal fluid

Who cannot join

  • Prior chemotherapy, biologic, targeted, or radiotherapy within 3 weeks prior to entering study or not recovered from grade >= 2 adverse events (AEs) due to agents administered more than 4 weeks earlier (except alopecia or neuropathy)
  • Prior MEK inhibitor or prior TAS-102 therapy
  • Use of other investigational drugs
  • History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity, or hypercoagulability syndromes)
  • History of retinal degenerative disease
  • History of Gilbert's syndrome
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  • Previous or concurrent malignancy with the following exceptions:
  • Adequately treated basal cell or squamous cell carcinoma of skin with adequate wound healing prior to study entry
  • In situ carcinoma of the cervix treated curatively and without evidence of recurrence
  • Primary malignancy completely resected and in complete remission >= 1 year
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft, coronary angioplasty, or stenting) < 6 months prior to screening
  • Impaired cardiovascular function or clinically significant cardiovascular disease including any of the following: symptomatic congestive heart failure, clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to screening except for atrial fibrillation and paroxysmal supraventricular tachycardia
  • Uncontrolled arterial hypertension despite appropriate medical therapy (systolic blood pressure > 160 or diastolic blood pressure > 100)
  • Neuromuscular disorders associated with elevated creatine kinase (CK, e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, or spinal muscular atrophy)
  • Started or planning to start on strenuous exercise regimen after first dose of study treatment (i.e., muscular activities, such as strenuous exercise, that can result in significant increase in plasma CK levels should be avoided while on trametinib treatment)
  • Gastrointestinal (GI) disease or impairment of GI function (e.g., active ulcerative disease, uncontrolled nausea, vomiting, or diarrhea, malabsorption syndrome, or small bowel resection)
  • Prior major surgery =< 3 weeks before study drug or not recovered from side effects of such procedure
  • Ongoing grade >= 3 neuropathy
  • Known hypersensitivity to any components of study drugs
  • Prior intolerance to a fluoropyrimidine
  • Any other condition that would, in the investigator's judgement, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medications, social/psychological issues, etc.)
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites
  • City of Hope Corona

    Corona, California, 92879

  • City of Hope Medical Center

    Duarte, California, 91010

  • City of Hope Antelope Valley

    Lancaster, California, 93534

  • City of Hope Mission Hills

    Mission Hills, California, 91345

  • City of Hope Rancho Cucamonga

    Rancho Cucamonga, California, 91730

  • City of Hope - Santa Clarita

    Santa Clarita, California, 91355

  • City of Hope South Pasadena

    South Pasadena, California, 91030

  • City of Hope West Covina

    West Covina, California, 91790

Other trials in United States

About this study

Official title: A Phase I Clinical Trial of Trametinib in Combination With TAS-102 in Patients With Chemotherapy-Resistant RAS-Mutated (PIK3CA/PTEN-Wild-Type) Metastatic Colorectal Cancer

This phase I trial studies the side effects and best dose of trametinib and trifluridine and tipiracil hydrochloride in treating patients with colon or rectal cancer that has spread to other places in the body (advanced/metastatic) or cannot be removed by surgery. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as trifluridine and tipiracil hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving trametinib and trifluridine and tipiracil hydrochloride may prevent cancer cells from dividing and work better in treating patients with colon and rectal cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose (MTD) for the combination of trametinib and trifluridine and tipiracil hydrochloride (TAS-102) in patients with chemotherapy-resistant metastatic colorectal cancer.

SECONDARY OBJECTIVES:

  1. Describe the safety of the combination of trametinib and TAS-102 across all investigated dose levels.

II. Describe the clinical activity including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the combination in an expansion cohort using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

OUTLINE:

Patients receive trifluridine and tipiracil hydrochloride orally (PO) twice daily (BID) on days 1-5 and 8-12 and trametinib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then bi-annually thereafter.

Being tested
Laboratory Biomarker Analysis, Trametinib, Trifluridine and Tipiracil Hydrochloride
Medical subject headings
Colonic Neoplasms, Colorectal Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • TrametinibDrug

    Also called GSK1120212, JTP-74057, MEK Inhibitor GSK1120212, Mekinist

    Given PO

  • Trifluridine and Tipiracil HydrochlorideDrug

    Also called Lonsurf, TAS 102, TAS-102, Tipiracil Hydrochloride Mixture with Trifluridine

    Given PO

Study groups in NCT03317119
Study groupRoleWhat they receive
Treatment (TAS-102, trametinib)ExperimentalPatients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and 8-12 and trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Drug: Trametinib; Drug: Trifluridine and Tipiracil Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose defined for the combination of trametinib, and Trifluridine and Tipiracil Hydrochloride (TAS?102) as the highest dose level at which 0-1 out of 6 patients experience dose limiting toxicities

    Toxicities observed at each dose level will be categorized by type (organ affected or laboratory determination such as absolute neutrophil count), severity (by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] 4.0 and nadir or maximum values for the laboratory measures), time of onset (i.e., course number), duration, and reversibility or outcome.

    Measured: Up to 28 days

Secondary outcomes (4)
  1. Incidence of adverse events assessed using NCI) CTCAE 4.0

    Will be summarized in terms of type and severity, along with dose modification/delays that resulted. Analysis will be primarily descriptive.

    Measured: Up to 30 after last dose

  2. Objective response rate using Response Evaluation Criteria in Solid Tumor (RECIST) guideline, version 1.1

    Measured: Up to 1 year

  3. Time to progression using RECIST guideline, version 1.1

    Measured: From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year

  4. Overall survival

    Measured: From start of treatment to death (any cause), assessed up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Oct 2017
  2. Study start11 Apr 2018
  3. Primary completion14 Jul 2023
  4. Study completion14 Jul 2023

Resources

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
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03317119
Sponsor's protocol ID
17212
Other IDs
NCI-2017-01923, 17212, P30CA033572
Status last verified
Apr 2024
First submitted
18 Oct 2017
Last updated
8 Apr 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Chuang J, Gong J, Li SM, Wang C, Fakih M. A Phase I Clinical Trial of Trametinib in Combination with TAS-102 in Patients with Chemotherapy-Resistant RAS-Mutated (PIK3CA/PTEN-Wild Type) Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2022 Sep;21(3):252-258. doi: 10.1016/j.clcc.2022.05.004. Epub 2022 May 23.

    PubMed 35738999

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Laboratory Biomarker Analysis, Trametinib and Trifluridine and Tipiracil Hydrochloride in people with Metastatic Colon Carcinoma and Metastatic Colorectal Carcinoma, run by City of Hope Medical Center at 8 sites in United States.

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 27 inclusion and 22 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: finished, as of the sponsor's last update on 8 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose defined for the combination of trametinib, and Trifluridine and Tipiracil Hydrochloride (TAS?102) as the highest dose level at which 0-1 out of 6 patients experience dose limiting toxicities (time frame: Up to 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03317119, which also lists 1 linked publication.

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 8 Apr 2024.

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