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Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS Mutant 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: NCT04735068
Recruitment Status : Recruiting
First Posted : February 2, 2021
Last Update Posted : July 26, 2021
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer KRAS Mutation-Related Tumors Drug: Binimetinib Pill Drug: Hydroxychloroquine Pill Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 9, 2021
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : February 2023

Resource links provided by the National Library of Medicine


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

Drug: Binimetinib Pill
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

Drug: Hydroxychloroquine Pill
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




Primary Outcome Measures :
  1. Objective Response Rate [ Time Frame: 2 years ]
  2. Number of Patients with Adverse Events as assessed by CTCAE v5.0 [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. progression-free survival (PFS) [ Time Frame: 2 years ]
  2. Number of changes in ctDNA KRAS allelic frequency (blood) [ Time Frame: 2 years ]
  3. Overall survival (OS) [ Time Frame: 2 years ]


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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

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): NCT04735068


Contacts
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Contact: Joshua Bauml, MD 215-662-4469 joshua.bauml@pennmedicine.upenn.edu
Contact: Melissa Volpe 215-220-9703 melissa.volpe@pennmedicine.upenn.edu

Locations
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United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Joshua Bauml, MD    855-216-0098    PennCancerTrials@emergingmed.com   
Principal Investigator: Josua Bauml, MD         
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
Pfizer
Investigators
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Principal Investigator: Joshua Bauml, MD Abramson Cancer Center of the University of Pennsylvania
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Responsible Party: Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT04735068    
Other Study ID Numbers: UPCC 21520
844511 ( Other Identifier: University of Pennsylvania Office of Regulatory Affairs )
First Posted: February 2, 2021    Key Record Dates
Last Update Posted: July 26, 2021
Last Verified: July 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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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
Hydroxychloroquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents