Clinical Trials /

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

NCT03704688

Description:

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.

Related Conditions:
  • Lung Adenocarcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 17-297
  • NCT ID: NCT03704688

Conditions

  • Non Small Cell Lung Cancer
  • KRAS Gene Mutation

Interventions

DrugSynonymsArms
Trametinib 0.5 mgPhase I: Dose Level -3
Trametinib 1 MGPhase I: Dose Level -2
Trametinib 1.5 MGPhase I: Dose Level -1
Trametinib 2 mgPhase I: Dose Level 1
Ponatinib 15 MGPhase I: Dose Level -3
Ponatinib 30 MGPhase I: Dose Level 2

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase I: Dose Level -3ExperimentalTrametinib 0.5mg PO q daily Ponatinib 15mg PO q daily
  • Trametinib 0.5 mg
  • Ponatinib 15 MG
Phase I: Dose Level -2ExperimentalTrametinib 1.0 mg PO q daily Ponatinib 15mg PO q daily
  • Trametinib 1 MG
  • Ponatinib 15 MG
Phase I: Dose Level -1ExperimentalTrametinib 1.5 mg PO q daily 15mg PO q daily
  • Trametinib 1.5 MG
  • Ponatinib 15 MG
Phase I: Dose Level 1ExperimentalTrametinib 2 mg PO q daily Ponatinib 15mg PO q daily
  • Trametinib 2 mg
  • Ponatinib 15 MG
Phase I: Dose Level 2ExperimentalTrametinib 2 mg PO q daily Ponatinib 30mg PO q daily
  • Trametinib 2 mg
  • Ponatinib 30 MG
Phase IIExperimentalMaximum tolerated dose as established in Phase I portion
  • Trametinib 2 mg
  • Ponatinib 15 MG

Eligibility Criteria

        Inclusion Criteria:

          -  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 inhibitor. Patients who are deemed not eligible for
             therapy with a PD-1 inhibitor by their treating physician will also be eligible.

          -  Able to take oral medications

          -  Measurable (RECIST 1.1) indicator lesion not previously irradiated

          -  Karnofsky performance status (KPS) ≥ 70%

          -  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 ≤ 51)

          -  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

        Exclusion Criteria:

          -  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

          -  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 within the past 6
             months. Note: Participants enrolled after this window must be on appropriate
             anti-platelet therapy

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose of Ponatinib and Trametinib
Time Frame:maximum of 18 months
Safety Issue:
Description:In the Phase I portion of the study, a standard 3+3 design will be used to find the maximum tolerated dose.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • trametinib
  • Ponatinib
  • KRAS Mutant Advanced Non-Small Cell Lung Cancer
  • 17-297
  • Memorial Sloan Kettering Cancer Center

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