Clinical Trials /

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

NCT04735068

Description:

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.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS Mutant Non-Small Cell Lung Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: UPCC 21520
  • SECONDARY ID: 844511
  • NCT ID: NCT04735068

Conditions

  • Non-Small Cell Lung Cancer
  • KRAS Mutation-Related Tumors

Interventions

DrugSynonymsArms
Binimetinib PillBinimetinib and Hydroxychloroquine
Hydroxychloroquine PillBinimetinib and Hydroxychloroquine

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Binimetinib and HydroxychloroquineExperimentalHydroxychloroquine (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
  • Binimetinib Pill
  • Hydroxychloroquine Pill

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:Objective Response Rate
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Abramson Cancer Center of the University of Pennsylvania

Last Updated

July 26, 2021