Honokiol in Early-Stage Resectable Non-Small Cell Lung Cancer

NCT06566443 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PRO00037422 (HMCC-LU22-001)
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I Trial evaluating the safety of the dietary supplement honokiol for lung cancer chemoprevention. Female or male patients aged 18 years, or older, with early stage lung cancer who have been scheduled for curative surgery will be eligible for participation in the study. The study will only enroll patients with stage I lung cancers less than 4 cm, given the recent approval of neoadjuvant chemotherapy and nivolumab for stage IB tumors \> 4 cm. Approximately, 15 patients will be enrolled in the study. They will take the study drug, honokiol, for 2 weeks prior to the surgery. The primary endpoint will be the Maximum Tolerated Dose (MTD) of honokiol.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose of Honokiol therapy

  To determine the maximum tolerated dose (MTD) of honokiol therapy in patients with stage I NSCLC, less than 4 cm, who will undergo surgical resection. Review the safety data to determine the dose level at which the maximum tolerable level of toxicity is observed and select as the MTD the dose for which the isotonic estimate of the DLT rate is closest to the target DLT rate.

  From treatment initiation of each patient, assessed up to 21 days after treatment initiation of final patient, up to 2 years after first enrollment.

Secondary Outcomes (4)

• Dose Limiting Toxicities of Honokiol therapy

  DLT period will start with initial treatment dose until 21 days after.

• Recommended Phase 2 Dose of Honokiol therapy

  From initial treatment dose until 21 days after.

• Number of participants with tumor necrosis

  From screening tissue collection to post-intervention tissue collection, an average of 3 months.

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  The safety period will start at baseline and will be assessed through study completion, up to 2 months

Other Outcomes (1)

• Tissue immune correlative biomarkers of honokiol therapy

  From pre-intervention blood collection to post-intervention blood collection, an average of 2 weeks.

Study Arms (1)

Honokiol

EXPERIMENTAL

Approximately, 15 patients will be enrolled in the study. They will take the study drug, honokiol, for 2 weeks prior to the surgery. The primary endpoint will be the maximum tolerated dose (MTD) of honokiol and this will be determined using Bayesian Optimal Interval Design (BOIN)

Drug: Honokiol

Interventions

Honokiol DRUG

Honokiol will be given orally at a starting dose of 1 capsule (250 mg/ capsule) per day for 2 weeks. Dose levels will escalate based on dose-limiting toxicity occurrence. We will start at one capsule (250 mg) once daily, dose 0 would be one capsule (250 mg) twice daily, dose +1 would be 500mg in the AM and 250mg in the evening, and +2 would be 500 mg twice daily.

Also known as: Honopure (Dietary supplement)

Honokiol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient provides written informed consent for the trial. Spanish speaking patients will be included and translation services will be provided as needed.
• Male or female, 18 years of age or older, on the day of informed consent signing.
• Early stage NSCLC eligible for upfront definitive surgical resection
• Measurable disease according to the Response evaluation criteria in solid tumors (RECIST 1.1) within 30 days of treatment.
• Expected life expectancy of at least 6 months
• Adequate organ and marrow function as defined below:
• Hemoglobin ≥9.0 g/dl (without blood transfusion within 2 weeks of laboratory test used to determine eligibility) Absolute neutrophil count ≥1000/μL (without granulocyte colony stimulating factor support within 2 weeks of laboratory test used to determine eligibility) Platelet count ≥100,000/μL (without transfusion within 2 weeks of laboratory test used to determine eligibility)- Serum total bilirubin (TB) ≤1.5 x institutional upper limit of normal (ULN; In the case of known Gilbert's syndrome, a higher serum TB \[\>1.5 x ULN\] is allowed), Aspartate transaminase/alanine transaminase ≤5 x institutional ULN Creatinine ≤1.5X the ULN or measured creatinine clearance ≥ 60 mL/min/1.
• Willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits and examinations.

You may not qualify if:

• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 3 weeks of trial treatment administration.
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to trial treatment administration or who has not recovered (i.e., ≤ Grade 1 or at baseline) from Adverse Events (AEs) due to a previously administered agent.
• Use of agents that target the mitochondrial metabolism.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2.
• Patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Patients with ≤ Grade 2 neuropathy may be eligible. If patient received major surgery, she must have recovered adequately from the toxicity and/or complications from the intervention prior to starting the trial treatment.
• Active infection requiring systemic therapy.
• Confirmed positive pregnancy test in women of childbearing potential (WOCBP).

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead

Study Sites (1)

Houston Methodist Neal Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (23)

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• Xu HL, Tang W, Du GH, Kokudo N. Targeting apoptosis pathways in cancer with magnolol and honokiol, bioactive constituents of the bark of Magnolia officinalis. Drug Discov Ther. 2011 Oct;5(5):202-10. doi: 10.5582/ddt.2011.v5.5.202.

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• Chiang CK, Sheu ML, Hung KY, Wu KD, Liu SH. Honokiol, a small molecular weight natural product, alleviates experimental mesangial proliferative glomerulonephritis. Kidney Int. 2006 Aug;70(4):682-9. doi: 10.1038/sj.ki.5001617.

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• Chen YJ, Wu CL, Liu JF, Fong YC, Hsu SF, Li TM, Su YC, Liu SH, Tang CH. Honokiol induces cell apoptosis in human chondrosarcoma cells through mitochondrial dysfunction and endoplasmic reticulum stress. Cancer Lett. 2010 May 1;291(1):20-30. doi: 10.1016/j.canlet.2009.08.032. Epub 2009 Oct 31.

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• Hahm ER, Singh SV. Honokiol causes G0-G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity. Mol Cancer Ther. 2007 Oct;6(10):2686-95. doi: 10.1158/1535-7163.MCT-07-0217.

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• Tse AK, Wan CK, Shen XL, Yang M, Fong WF. Honokiol inhibits TNF-alpha-stimulated NF-kappaB activation and NF-kappaB-regulated gene expression through suppression of IKK activation. Biochem Pharmacol. 2005 Nov 15;70(10):1443-57. doi: 10.1016/j.bcp.2005.08.011. Epub 2005 Sep 21.

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• Deng J, Qian Y, Geng L, Chen J, Wang X, Xie H, Yan S, Jiang G, Zhou L, Zheng S. Involvement of p38 mitogen-activated protein kinase pathway in honokiol-induced apoptosis in a human hepatoma cell line (hepG2). Liver Int. 2008 Dec;28(10):1458-64. doi: 10.1111/j.1478-3231.2008.01767.x. Epub 2008 May 26.

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• Steinmann P, Walters DK, Arlt MJ, Banke IJ, Ziegler U, Langsam B, Arbiser J, Muff R, Born W, Fuchs B. Antimetastatic activity of honokiol in osteosarcoma. Cancer. 2012 Apr 15;118(8):2117-27. doi: 10.1002/cncr.26434. Epub 2011 Sep 20.

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• Hu H, Zhang XX, Wang YY, Chen SZ. Honokiol inhibits arterial thrombosis through endothelial cell protection and stimulation of prostacyclin. Acta Pharmacol Sin. 2005 Sep;26(9):1063-8. doi: 10.1111/j.1745-7254.2005.00164.x.

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Related Links

• Honokiol, magnolia bark, A miracle cure for cancer?
• Bayesian Optimal Interval Designs for Phase I Clinical Trials

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

honokiol; Dietary Supplements

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Jun Zhang, MD

  Houston Methodist Neal Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Zhang, MD

CONTACT

713-441-6698; jzhang22@houstonmethodist.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Thoracic Oncology

Study Record Dates

• First Submitted: August 9, 2024
• First Posted: August 22, 2024
• Study Start: February 13, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: May 28, 2026

Record last verified: 2026-05

Locations

US (1)