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.
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
Drug | Synonyms | Arms |
---|
Binimetinib Pill | | Binimetinib and Hydroxychloroquine |
Hydroxychloroquine Pill | | Binimetinib 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
Name | Type | Description | Interventions |
---|
Binimetinib and Hydroxychloroquine | Experimental | 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 | - 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