Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS Mutant Non-Small Cell Lung Cancer

June 27, 2023 updated by: Abramson Cancer Center at Penn Medicine

The LIMIT KRAS Mutant NSCLC Trial: Lysosome Inhibition to Enhance MAPK Inhibition Targeting KRAS Mutant NSCLC: A Phase 2 Open Label Trial of Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS Mutant Non-Small Cell Lung Cancer

This study will evaluate using hydroxychloroquine (HCQ) along with binimetinib as an effective method for treating cancer. All patients will receive binimetinib at a standard dose approved for other cancers. The dose of HCQ will also be fixed based on ongoing phase I studies. Eligible subjects will have lung cancer that has a mutation in a key cancer gene called KRAS, and the cancer has spread to other parts of their body.

Study Overview

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Abramson Cancer Center of the University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Metastatic or incurable NSCLC
  2. Presence of a non-synonymous mutation in KRAS
  3. Patient must have received at least one prior systemic therapy for metastatic NSCLC or be intolerant/ineligible/refuse available therapies with known benefit
  4. Ability and willingness to sign a written informed consent document
  5. Age ≥18 years old
  6. At least one measureable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  7. ECOG performance status 0-1
  8. Adequate organ function
  9. Women of childbearing potential must have a negative serum pregnancy test performed within 72hours of the first dose of study therapy. Subjects of reproductive potential must agree to use acceptable birth control methods (see Appendix B for childbearing potential).
  10. Qtc < 500 mSec on EKG
  11. Must be able to swallow tablets
  12. Must be willing to comply with protocol procedures (including completion of diaries and outcome measures

Exclusion Criteria:

  1. Currently participating in or has participated in a study of an investigational agent or anticipated use of an investigational device within 4 weeks of the first dose of study treatment.
  2. Untreated symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
  3. Prior monoclonal antibody within 4 weeks prior to enrollment, or individuals who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  4. Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, non-invasive bladder tumors, or in situ cervical cancer
  5. Active infection requiring systemic therapy with IV antibiotics
  6. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  7. Known psychiatric or substance abuse disorders as documented in the chart that, in the opinion of the investigator, would interfere with cooperation with the requirements of the trial.
  8. Pregnant or breastfeeding women
  9. Anticipated receipt of any live vaccine within 30 days prior to the first dose of trial treatment.
  10. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO).
  11. Patients receiving cytochrome P450 enzyme-inducing anticonvulsant drugs (EIADs) (i.e.

    phenytoin, carbamazepine, Phenobarbital, primidone or oxcarbazepine) within 4 weeks of the start of the study treatment

  12. Known Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (subjects with laboratory evidence of cleared HBV and/or HCV will be permitted)
  13. Patients with a previously documented retinal vein occlusion.
  14. History or evidence of increased cardiovascular risk including any of the following:

    • Current clinically significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible.
    • History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization.
    • Ejection fraction of ≤50% as measured by echocardiography or MUGA
  15. Any other conditions judged by the investigator that would limit the evaluation of the subject

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Binimetinib and Hydroxychloroquine

Hydroxychloroquine (HCQ)in combination with Binimetinib (B). The starting dose for HCQ will be 400mg. Tablets of HCQ are available in 200 mg strength. HCQ will be administered in divided doses (every 12 hours) with or without food.

The starting dose of B is 45mg. B will be administered in divided doses (every 12 hours) with or without food

Patients will be treated with B 45 mg two times daily and HCQ 400 mg twice daily beginning on day 1. The dose of HCQ is based on an ongoing Phase 1 trial, and may be modified in a future amendment prior to the first patient enrolled. Efforts will be made to ensure dose homogeneity throughout the trial. Treatment will be administered on an outpatient basis on a 28 day cycle
Patients will be treated with B 45 mg two times daily and HCQ 400 mg twice daily beginning on day 1. The dose of HCQ is based on an ongoing Phase 1 trial, and may be modified in a future amendment prior to the first patient enrolled. Efforts will be made to ensure dose homogeneity throughout the trial. Treatment will be administered on an outpatient basis on a 28 day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Objective Response Rate
Time Frame: 2 years
2 years
Number of Patients with Adverse Events as assessed by CTCAE v5.0
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival (OS)
Time Frame: 2 years
2 years
progression-free survival (PFS)
Time Frame: 2 years
2 years
Number of changes in ctDNA KRAS allelic frequency (blood)
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Charu Aggarwal, MD, Abramson Cancer Center at Penn Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 9, 2021

Primary Completion (Actual)

August 21, 2022

Study Completion (Estimated)

December 1, 2023

Study Registration Dates

First Submitted

January 11, 2021

First Submitted That Met QC Criteria

January 28, 2021

First Posted (Actual)

February 2, 2021

Study Record Updates

Last Update Posted (Actual)

June 29, 2023

Last Update Submitted That Met QC Criteria

June 27, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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