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

Официальное название

Phase I Trial Evaluating the Safety of the Dietary Supplement Honokiol in Early-Stage Resectable Non-Small Cell Lung Cancer

Обзор

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.

Вмешательства

• Препарат Honokiol
  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.

Первичные конечные точки

• Maximum Tolerated Dose of Honokiol therapy [Срок оценки: From treatment initiation of each patient, assessed up to 21 days after treatment initiation of final patient, up to 2 years after first enrollment.]

Вторичные конечные точки (4)

• Dose Limiting Toxicities of Honokiol therapy [Срок оценки: DLT period will start with initial treatment dose until 21 days after.]
• Recommended Phase 2 Dose of Honokiol therapy [Срок оценки: From initial treatment dose until 21 days after.]
• Number of participants with tumor necrosis [Срок оценки: 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 [Срок оценки: The safety period will start at baseline and will be assessed through study completion, up to 2 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

США · 1 центр

• Houston Methodist Neal Cancer Center — Houston

Публикации

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• Lampidis TJ, Bernal SD, Summerhayes IC, Chen LB. Selective toxicity of rhodamine 123 in carcinoma cells in vitro. Cancer Res. 1983 Feb;43(2):716-20. PMID 6848187
• Pathania D, Millard M, Neamati N. Opportunities in discovery and delivery of anticancer drugs targeting mitochondria and cancer cell metabolism. Adv Drug Deliv Rev. 2009 Nov 30;61(14):1250-75. doi: 10.1016/j.addr.2009.05.010. Epub 2009 Aug 27. PMID 19716393
• Chen F, Wang T, Wu YF, Gu Y, Xu XL, Zheng S, Hu X. Honokiol: a potent chemotherapy candidate for human colorectal carcinoma. World J Gastroenterol. 2004 Dec 1;10(23):3459-63. doi: 10.3748/wjg.v10.i23.3459. PMID 15526365

Идентификаторы

NCT: NCT06566443 · PRO00037422 (HMCC-LU22-001)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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