Non-Small Cell Lung CancerPhase 2NCT04735068
Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS Mutant Non-Small Cell Lung Cancer
A Phase 2 study testing Binimetinib Pill and Hydroxychloroquine Pill in people with Non-Small Cell Lung Cancer and KRAS Mutation-Related Tumors, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Non-Small Cell Lung Cancer, KRAS Mutation-Related Tumors
- What is being tested?
- Binimetinib Pill and Hydroxychloroquine Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Apr 2021to 31 Dec 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Metastatic or incurable NSCLC
- Presence of a non-synonymous mutation in KRAS
- Patient must have received at least one prior systemic therapy for metastatic NSCLC or be intolerant/ineligible/refuse available therapies with known benefit
- Ability and willingness to sign a written informed consent document
- Age ≥18 years old
- At least one measureable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
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- ECOG performance status 0-1
- Adequate organ function
- 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).
- Qtc < 500 mSec on EKG
- Must be able to swallow tablets
- Must be willing to comply with protocol procedures (including completion of diaries and outcome measures
Who cannot join
- 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.
- Untreated symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
- 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.
- 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
- Active infection requiring systemic therapy with IV antibiotics
- 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.
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- 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.
- Pregnant or breastfeeding women
- Anticipated receipt of any live vaccine within 30 days prior to the first dose of trial treatment.
- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO).
- 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
- Known Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (subjects with laboratory evidence of cleared HBV and/or HCV will be permitted)
- Patients with a previously documented retinal vein occlusion.
- 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
- Any other conditions judged by the investigator that would limit the evaluation of the subject
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
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
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.
- Being tested
- Binimetinib Pill, Hydroxychloroquine Pill
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Binimetinib PillDrug
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
Hydroxychloroquine PillDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Binimetinib Pill; Drug: Hydroxychloroquine Pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: 16 months
Number of Patients With Adverse Events
as assessed by CTCAE v5.0
Measured: 16 months
Secondary outcomes (2)
Progression-free Survival (PFS)
Measured: 16 months
Overall Survival (OS)
Measured: 16 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2021
- Study start9 Apr 2021
- Primary completion21 Aug 2022
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Charu Aggarwal, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04735068
- Sponsor's protocol ID
- UPCC 21520
- Other IDs
- 844511
- Status last verified
- Mar 2025
- First submitted
- 11 Jan 2021
- Last updated
- 1 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Aggarwal C, Maity AP, Bauml JM, Long Q, Aleman T, Ciunci C, D'Avella C, Volpe M, Anderson E, Jones LM, Sun L, Singh AP, Marmarelis ME, Cohen RB, Langer CJ, Amaravadi R. A Phase II Open-Label Trial of Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS-Mutant Non-Small Cell Lung Cancer. Oncologist. 2023 Jul 5;28(7):644-e564. doi: 10.1093/oncolo/oyad106.
PubMed 37186063
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04735068
- Acronym / sponsor ID
- UPCC 21520
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 9 Apr 2021 (actual)
- Primary completion
- 21 Aug 2022 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 2 Feb 2021 (actual)
- Results
- Posted 1 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Binimetinib and Hydroxychloroquine | Experimental | Drug: Binimetinib Pill, Drug: Hydroxychloroquine PillHydroxychloroquine (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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Metastatic or incurable NSCLC
- Presence of a non-synonymous mutation in KRAS
- Patient must have received at least one prior systemic therapy for metastatic NSCLC or be intolerant/ineligible/refuse available therapies with known benefit
- Ability and willingness to sign a written informed consent document
- Age ≥18 years old
Key exclusion criteria (19 listed)
- 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.
- Untreated symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
- 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.
- 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
- Active infection requiring systemic therapy with IV antibiotics
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Binimetinib PillPatients 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 | Binimetinib and Hydroxychloroquine |
| Hydroxychloroquine PillPatients 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 | Binimetinib and Hydroxychloroquine |
Primary outcome
Objective Response Rate
Time frame: 16 months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Number of Patients With Adverse Events
Time frame: 16 months
as assessed by CTCAE v5.0
2 secondary outcomes
Progression-free Survival (PFS)
Time frame: 16 months
Overall Survival (OS)
Time frame: 16 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37186063Aggarwal C, Maity AP, Bauml JM, Long Q, Aleman T, Ciunci C, D'Avella C, Volpe M, Anderson E, Jones LM, Sun L, Singh AP, Marmarelis ME, Cohen RB, Langer CJ, Amaravadi R. A Phase II Open-Label Trial of Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS-Mutant Non-Small Cell Lung Cancer. Oncologist. 2023 Jul 5;28(7):644-e564. doi: 10.1093/oncolo/oyad106.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charu Aggarwal, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Binimetinib Pill and Hydroxychloroquine Pill in people with Non-Small Cell Lung Cancer and KRAS Mutation-Related Tumors, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (time frame: 16 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04735068, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2025.