Study to Assess the Safety, Tolerability of JPI-547 in Combination With Modified FOLFIRINOX or Gemcitabine-nab-paclitaxel in Patients With Locally Advanced and Metastatic Pancreatic Cancer

Официальное название

An Open-label, Dose-finding, Phase Ib/II Study to Assess the Safety, Tolerability of JPI-547, a Dual Inhibitor of PARP/Tankyrase, in Combination With Modified FOLFIRINOX (mFOLFIRINOX) or Gemcitabine-nab-paclitaxel (GemAbraxne) in Patients With Locally Advanced and Metastatic Pancreatic Cancer

Обзор

The purpose of this study is to assess the safety, tolerability and efficacy of JPI-547 in combination with modified FOLFIRINOX (mFOLFIRINOX) or Gemcitabine-nab-paclitaxel (GemAbraxne) in patients with locally advanced and metastatic pancreatic cancer

Подробное описание

In combination with JPI-547 and chemotherapy in patients with locally advanced/metastatic pancreatic cancer,

Primary Objectives

* To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). * To select the optimal combination chemotherapy based on the safety profile.

Secondary Objectives

* To assess the safety and toxicity. * To evaluate anti-tumor activity.

Вмешательства

• Препарат JPI-547
  * Subjects are administered this investigational product once a week for 5 days, and have wash-out period for 2 days (5 Days on-2 Days off). * The investigational product is administered orally in a fasting state for 2 hours before and after meals at the same time (e.g., a certain time in the morning). * Capsules should be swallowed whole and should not be chewed, crushed or split.
• Препарат modified FOLFIRINOX
  * After IV administration of Oxaliplatin 65 mg/m2 for 2 hours * After IV administration of Leucovorin 400 mg/m2 for 2 hours + IV administration of Irinotecan 135 mg/m2 for 90 minutes (Irinotecan is started 30 minutes after the start of Leucovorin administration and administered simultaneously during the last 90 minutes of Leucovorin administration, but administered separately using a Y-connector without mixing) * Continuous IV infusion of 5-FU 2400 mg/m2 for 46 hours * Repeated administration ev
• Препарат Gemcitabine-nab-paclitaxel
  * After IV administration of nab-paclitaxel 125 mg/m2 for 30 minutes * IV administration of Gemcitabine 1000 mg/m2 for 30 minutes * Administration on Days 1, 8, and 15 on a 28-day cycle

Первичные конечные точки

• Phase 1b: Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). [Срок оценки: From the date of administration to 4 weeks (DLT period)]
• Phase 2: To determine the regimen of JPI-547 in combination with Chemotherapy GemAbraxane and to evaluate the potential antitumor activity and safety of the combination therapy. [Срок оценки: From first dose until disease progression, assessed up to end of study]

Вторичные конечные точки (2)

• To assess the adverse events, drug adverse events, and serious adverse events evaluated by NCI-CTCAE v5.0 [Срок оценки: Until 4 weeks after the last dose administration]
• To evaluate anti-tumor activity. [Срок оценки: Evaluation at 8 weeks intervals through study completion from the date of study entry until the date of progression, up to 18 months]

Критерии участия

Критерии включения

\[Phase 1b/2\]

• Histologically or cytologically confirmed inoperable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC)
• Those with at least one measurable lesion in accordance with RECIST 1.1
• Those with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Those with an expected survival period ≥12 weeks
• Patients with adequate hematologic function, renal and hepatic function confirmed by the following criteria (During the screening period, laboratory tests can be retested only once.)
• Those who voluntarily decide to participate in this clinical study after hearing sufficient explanations and who consent in writing

\[only to Phase 2\]

1\. Subjects from whom tumor tissue samples can be obtained at screening and who meet at least one of the following criteria:

• Tumor tissue samples stored prior to screening are available
• Tumor tissue samples can be obtained at screening with the subject's consent to biopsy

Критерии исключения

\[Phase 1b/2\]

• Those with a history of severe hypersensitivity to the investigational product or combination anticancer drugs.
• Those with the following medical history or surgical history/procedural history confirmed

• Other primary malignant tumors other than pancreatic cancer
• Major surgery that requires general anesthesia or breathing aid
• Severe cardiovascular disease
• New York Heart Association Class 3 or 4 heart failure
• Severe cerebrovascular disease t
• Pulmonary thrombosis, deep vein thrombosis, or bronchial asthma, obstructive pulmonary disease, and other life-threatening severe lung diseases
• Infections requiring administration of systemic antibiotics or antivirals, etc.
• Hematologic malignancy
• Those with the following diseases

• Massive ascites, pleural effusions requiring therapeutic paracentesis
• Neuropathy ≥Grade 2
• Diarrhea, chronic inflammatory bowel disease
• Intestinal paralysis, intestinal obstruction
• Diseases that make oral administration difficult or affect absorption
• Interstitial lung disease, pulmonary fibrosis
• Dialysis patient
• Patients with clinically significant symptoms or uncontrolled central nervous system or brain metastases

j. Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure >90 mmHg) k. Bleeding diatheses l. Active hepatitis B or C virus. m. Known human immunodeficiency virus (HIV) positive

• Those with a medication history of the following drugs

• Anti-cancer drug therapy such as chemotherapy and biological therapy
• Radiation therapy within 2 weeks of baseline
• Those who are taking or expected to require administration of strong inhibitors or inducers of CYP3A4
• (For mFOLFIRINOX cohort) Those who are taking or expected to require administration of sorivudine
• Patients who require continuous administration of non-steroidal anti-inflammatory drugs (NSAIDs) with high bleeding risk
• Patients requiring continuous administration of systemic corticosteroid equivalent to prednisone >10 mg/day
• Those who have received antithrombotic agents, including antiplatelet agents, anticoagulants, etc.
• Pregnant women, lactating women, or women of childbearing potential and men who do not intend to practice abstinence or use appropriate contraceptive methods for until 6 months for men and 9 months for women after administration of the investigational product and during the clinical study
• Those who have administered other investigational products or have received investigational medical device procedures within 4 weeks of the baseline
• Other patients who are inappropriate or unable to participate in this clinical study at the discretion of the investigator

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

South Korea · 4 центра

• Seoul National University Bundang Hospital — Gyeonggi-do
• Samsung Medical Center — Seoul
• Seoul national university hospital — Seoul
• Severance Hospital — Seoul

Идентификаторы

NCT: NCT05257993 · JPI-547-102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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