Honokiol in Early-Stage Resectable Non-Small Cell Lung Cancer
ConditionCarcinoma, Non-Small-Cell Lung
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorThe Methodist Hospital Research Institute
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Sequential
Treatments tested in this trial
Honokiol
DrugHonokiol 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.
Treatment groups
15 Participants
are divided into 1 treatment groupGroup A: HonokiolExperimental treatment 1 intervention
Trial outcomes
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.
Time frame
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
1
Dose Limiting Toxicities of Honokiol therapy
To determine the dose-limiting toxicity (DLT) and other toxicities associated with honokiol therapy, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0;
Time frame
DLT period will start with initial treatment dose until 21 days after.2
Recommended Phase 2 Dose of Honokiol therapy
To determine the recommended Phase II dose (RP2D) of honokiol; Bayesian Optimal Interval (BOIN) design will be used for dose finding.
Time frame
From initial treatment dose until 21 days after.3
Number of participants with tumor necrosis
To assess for any evidence of tumor necrosis.
Time frame
From screening tissue collection to post-intervention tissue collection, an average of 3 months.4
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
To determine the safety and tolerability of honokiol therapy prior to surgery as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
Time frame
The safety period will start at baseline and will be assessed through study completion, up to 2 monthsOther outcomes
1
Tissue immune correlative biomarkers of honokiol therapy
To evaluate tissue immune correlative biomarkers of honokiol therapy, including but not limited to Ki67, a good standard for the measurement of cell proliferation.
Time frame
From pre-intervention blood collection to post-intervention blood collection, an average of 2 weeks.Sponsors and contacts
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Source ClinicalTrials.gov