Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03704688
Recruitment Status : Recruiting
First Posted : October 15, 2018
Last Update Posted : October 11, 2019
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief 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.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer KRAS Gene Mutation Drug: Trametinib 0.5 mg Drug: Trametinib 1 MG Drug: Trametinib 1.5 MG Drug: Trametinib 2 mg Drug: Ponatinib 15 MG Drug: Ponatinib 30 MG Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 37 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Trial of Trametinib and Ponatinib in Patients With KRAS Mutant Advanced Non-Small Cell Lung Cancer
Actual Study Start Date : October 9, 2018
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Phase I: Dose Level -3
Trametinib 0.5mg PO q daily Ponatinib 15mg PO q daily
Drug: Trametinib 0.5 mg
0.5mg PO q daily

Drug: Ponatinib 15 MG
15mg PO q daily

Experimental: Phase I: Dose Level -2
Trametinib 1.0 mg PO q daily Ponatinib 15mg PO q daily
Drug: Trametinib 1 MG
1.0 mg PO q daily

Drug: Ponatinib 15 MG
15mg PO q daily

Experimental: Phase I: Dose Level -1
Trametinib 1.5 mg PO q daily 15mg PO q daily
Drug: Trametinib 1.5 MG
1.5mg PO q daily

Drug: Ponatinib 15 MG
15mg PO q daily

Experimental: Phase I: Dose Level 1
Trametinib 2 mg PO q daily Ponatinib 15mg PO q daily
Drug: Trametinib 2 mg
2 mg PO q daily

Drug: Ponatinib 15 MG
15mg PO q daily

Experimental: Phase I: Dose Level 2
Trametinib 2 mg PO q daily Ponatinib 30mg PO q daily
Drug: Trametinib 2 mg
2 mg PO q daily

Drug: Ponatinib 30 MG
30mg PO q daily

Experimental: Phase II
Maximum tolerated dose as established in Phase I portion
Drug: Trametinib 2 mg
2 mg PO q daily

Drug: Ponatinib 15 MG
15mg PO q daily




Primary Outcome Measures :
  1. Maximum Tolerated Dose of Ponatinib and Trametinib [ Time Frame: maximum of 18 months ]
    In the Phase I portion of the study, a standard 3+3 design will be used to find the maximum tolerated dose.

  2. Overall Response Rate [ Time Frame: 1 year ]
    In the Phase II portion of the study, RECIST criteria 1.1 will evaluate the overall response rate.



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.


Layout table for eligibility information
Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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/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%
  • 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

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.
  • 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

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): NCT03704688


Contacts
Layout table for location contacts
Contact: Kathryn Arbour, MD 646-449-1775 arbourk@mskcc.org
Contact: Gregory Riely, MD, PhD 646-888-4199 rielyg@mskcc.org

Locations
Layout table for location information
United States, New Jersey
Memoral Sloan Kettering Basking Ridge (Limited Protocol Activities) Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Kathryn Arbour, MD    646-449-1775      
Memoral Sloan Kettering Monmouth (Limited Protocol Activities) Recruiting
Middletown, New Jersey, United States, 07748
Contact: Kathryn Arbour, MD    646-449-1775      
Memorial Sloan Kettering Bergen (Limited Protocol Activities) Recruiting
Montvale, New Jersey, United States, 07645
Contact: Kathryn Arbour, MD    646-449-1775      
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk (Limited protocol activity) Recruiting
Commack, New York, United States, 11725
Contact: Kathryn Arbour, MD    646-449-1775      
Memoral Sloan Kettering Westchester (Limited Protocol Activities) Recruiting
Harrison, New York, United States, 10604
Contact: Kathryn Arbour, MD    646-449-1775      
Memorial Sloan - Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Contact: Kathryn Arbour, MD    646-449-1775      
Memorial Sloan Kettering Nassau (Limited protocol activity) Recruiting
Uniondale, New York, United States, 11553
Contact: Kathryn Arbour, MD    646-449-1775      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
Layout table for investigator information
Principal Investigator: Kathryn Arbour, MD Memorial Sloan Kettering Cancer Center

Additional Information:
Layout table for additonal information
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03704688     History of Changes
Other Study ID Numbers: 17-297
First Posted: October 15, 2018    Key Record Dates
Last Update Posted: October 11, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
trametinib
Ponatinib
KRAS Mutant Advanced Non-Small Cell Lung Cancer
17-297
Memorial Sloan Kettering Cancer Center
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Trametinib
Ponatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action