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Non Small Cell Lung CancerPhase 1/2NCT03704688

Trial of Trametinib and Ponatinib in Patients With KRAS Mutant Advanced Non-Small Cell Lung Cancer

A Phase 1/2 study testing Trametinib 0.5 mg, Trametinib 1 MG and Trametinib 1.5 MG in people with Non Small Cell Lung Cancer and KRAS Gene Mutation, run by Memorial Sloan Kettering Cancer Center at 7 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

The purpose of this study is to evaluate the safety of the combination of ponatinib and trametinib as well as the most appropriate dosages of the combination. Read more about this study

Who is it for?
Ages 19 years and older
What is being tested?
Trametinib 0.5 mg, Trametinib 1 MG and Trametinib 1.5 MG
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
7 sitesUnited States
Study dates
9 Oct 2018to 4 Feb 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically proven diagnosis of advanced lung adenocarcinoma
  • KRAS mutation
  • Radiographic progression following prior treatment with platinum doublet chemotherapy and prior treatment with a PD-1/L1 inhibitor. Patients who are deemed not eligible for therapy with a PD-1/L1 inhibitor by their treating physician will also be eligible.
  • Able to take oral medications
  • Measurable disease as per RECIST 1.1. Previously irradiated sites of tumor may be considered measurable if there is radiographic progression at the site subsequent to the time of completing radiation.
  • Karnofsky performance status (KPS) ≥ 70%
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  • Age >18 years old
  • Adequate organ function:
  • AST, ALT ≤ 2.5 x ULN - Total bilirubin ≤ 1.5 x ULN -Albumin ≥ 2.5g/dL
  • Creatinine < 1.5 x ULN OR calculated creatinine clearance ≥ 50mL/min
  • Absolute neutrophil count (ANC) ≥ 1,200 cells/mm^3
  • Hemoglobin ≥ 9.0 g/dL
  • Platelets ≥ 100,000/mm^3
  • Amylase and lipase within normal limits (amylase ≤ 100, lipase ≤ 78)
  • Female patients who:
  • Are postmenopausal for at least 1 year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
  • Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study drug, or
  • Agree to completely abstain from heterosexual intercourse

Who cannot join

  • Patients with symptomatic brain metastasis requiring escalating doses of steroids
  • Patients with grade 2 or greater diarrhea prior to study initiation despite maximal medical management
  • History of acute pancreatitis within 1 year of study entry or history of chronic pancreatitis
  • History of or ongoing alcohol abuse that, in the opinion of the Investigator, would compromise compliance or impart excess risks associated with study participation.
  • Pregnant or lactating women
  • Any type of systemic therapy (chemotherapy or experimental drugs) within 2 weeks of starting treatment on protocol
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  • Patients who have received prior treatment with MEK inhibitor
  • A history of clinically significant interstitial lung disease or pneumonitis
  • Significant uncontrolled or active cardiovascular disease, specifically including, but not restricted to: History of clinically significant (as determined by the treating physician) atrial arrhythmia; or any ventricular arrhythmia, History of congenital long QT syndrome., Abnormal QTc (≥ 450 msec in males and ≥ 470 msec in females), Ejection fraction ≤ 50% as assessed by echocardiogram.
  • History of arterial thrombotic disease, specifically including, but not restricted to: Myocardial infarction or unstable angina, cerebrovascular event (CVA) or transient ischemic attack (TIA), Peripheral vascular disease or claudication.
  • Uncontrolled hypertension (Diastolic blood pressure > 100 mmHg; Systolic blood pressure > 150 mmHg).
  • History of venous thromboembolism (e.g. deep venous thrombosis or pulmonary embolism) within 6 months of study entry. Note: Participants enrolled after this window must be on appropriate therapeutic anticoagulation.
  • History of central serous retinopathy or retinal vein occlusion
  • Patients with baseline risk factors for central serous retinopathy or retinal vein occlusion such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure >21 mmHg are excluded from the trial
  • History of prior malignancy within 2 years that requires treatment. Patients who are considered NED from a malignancy may be considered on a case by case basis.
  • Any other condition that, in the opinion of the investigator, may compromise the safety, compliance of the patient, or would preclude the patient from successful completion of the study

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

    Basking Ridge, New Jersey, 07920

  • Memorial Sloan Kettering Cancer Center @ Suffolk (Limited protocol activity)

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester (Limited Protocol Activities)

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)

    Montvale, New Jersey, 07645

  • Memorial Sloan - Kettering Cancer Center

    New York, New York, 10021

  • Memorial Sloan Kettering Nassau (Limited protocol activity)

    Uniondale, New York, 11553

Other trials in United States

About this study

Official title: A Phase 1 Trial of Trametinib and Ponatinib in Patients With KRAS Mutant Advanced Non-Small Cell Lung Cancer

The purpose of this study is to evaluate the safety of the combination of ponatinib and trametinib as well as the most appropriate dosages of the combination.

Being tested
Trametinib 0.5 mg, Trametinib 1 MG, Trametinib 1.5 MG, Trametinib 2 mg, Ponatinib 15 MG
Keywords
trametinib, Ponatinib, KRAS Mutant Advanced Non-Small Cell Lung Cancer, 17-297, Memorial Sloan Kettering Cancer Center
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • Trametinib 0.5 mgDrug

    0.5mg PO q daily

  • Trametinib 1 MGDrug

    1.0 mg PO q daily

  • Trametinib 1.5 MGDrug

    1.5mg PO q daily

  • Trametinib 2 mgDrug

    2 mg PO q daily

  • Ponatinib 15 MGDrug

    15mg PO q daily

  • Ponatinib 30 MGDrug

    30mg PO q daily

Study groups in NCT03704688
Study groupRoleWhat they receive
Phase I: Dose Level -3ExperimentalTrametinib 0.5mg PO q daily Ponatinib 15mg PO q daily
Receives: Drug: Trametinib 0.5 mg; Drug: Ponatinib 15 MG
Phase I: Dose Level -2ExperimentalTrametinib 1.0 mg PO q daily Ponatinib 15mg PO q daily
Receives: Drug: Trametinib 1 MG; Drug: Ponatinib 15 MG
Phase I: Dose Level -1ExperimentalTrametinib 1.5 mg PO q daily 15mg PO q daily
Receives: Drug: Trametinib 1.5 MG; Drug: Ponatinib 15 MG
Phase I: Dose Level 1ExperimentalTrametinib 2 mg PO q daily Ponatinib 15mg PO q daily
Receives: Drug: Trametinib 2 mg; Drug: Ponatinib 15 MG
Phase I: Dose Level 2ExperimentalTrametinib 2 mg PO q daily Ponatinib 30mg PO q daily
Receives: Drug: Trametinib 2 mg; Drug: Ponatinib 30 MG
Phase IIExperimentalMaximum tolerated dose as established in Phase I portion
Receives: Drug: Trametinib 2 mg; Drug: Ponatinib 15 MG

What is being measured

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

  1. Maximum Tolerated Dose of Ponatinib, Phase I

    In the Phase I portion of the study, a standard 3+3 design will be used to find the maximum tolerated dose.

    Measured: maximum of 18 months

  2. Overall Response Rate

    In the Phase II portion of the study, RECIST criteria 1.1 will evaluate the overall response rate. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: 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 posted15 Oct 2018
  2. Study start9 Oct 2018
  3. Primary completion4 Feb 2022
  4. Study completion4 Feb 2022

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03704688
Sponsor's protocol ID
17-297
Status last verified
Feb 2022
First submitted
10 Oct 2018
Last updated
16 May 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Trametinib 0.5 mg, Trametinib 1 MG and Trametinib 1.5 MG in people with Non Small Cell Lung Cancer and KRAS Gene Mutation, run by Memorial Sloan Kettering Cancer Center at 7 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 21 inclusion and 16 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 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 of Ponatinib, Phase I (time frame: maximum of 18 months). The study lists 2 primary outcomes in all. 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 NCT03704688.

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 16 May 2025.

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