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
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the safety, tolerability of JPI-547 in combination with modified FOLFIRINOX (mFOLFIRINOX) or Gemcitabine-nab-paclitaxel (GemAbraxne) in patients with locally advanced and metastatic pancreatic cancer
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
In combination with JPI-547 and chemotherapy in patients with locally advanced/metastatic pancreatic cancer,
Primary Objectives
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To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D).
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To select the optimal combination chemotherapy based on the safety profile.
Secondary Objectives
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To assess the safety and toxicity.
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To evaluate anti-tumor activity.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm A (mFOLFIRINOX) JPI-547 and Combination Chemotherapy(mFOLFIRINOX) The study is conducted in a 3+3 dose escalation method. |
Drug: 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.
Drug: 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 every 2 weeks on a 14-day cycle
|
| Experimental: Arm B (GemAbraxane) JPI-547 and Combination Chemotherapy (Gemcitabine-nab-paclitaxel) The study is conducted in a 3+3 dose escalation method. |
Drug: 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.
Drug: Gemcitabine-nab-paclitaxel
After IV administration of nab-paclitaxel 100 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
|
Outcome Measures
Primary Outcome Measures
- Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). [From the date of administration to 4 weeks (DLT period)]
The MTD is determined according to the traditional 3+3 rule-based method for each combination therapy, and it is defined as the highest dose with a DLT incidence of less than 1/3 or 2/6 subjects.
Secondary Outcome Measures
- To assess the adverse events, drug adverse events, and serious adverse events evaluated by NCI-CTCAE v5.0 [Until 4 weeks after the last dose administration]
- To evaluate anti-tumor activity. [Evaluation at 8 weeks intervals through study completion from the date of study entry until the date of progression, up to 18 months]
Anti-tumor activity is evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically or cytologically confirmed inoperable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC)
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Those with at least one measurable lesion in accordance with RECIST 1.1
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Those with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
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Those with an expected survival period ≥12 weeks
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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.)
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Those who voluntarily decide to participate in this clinical study after hearing sufficient explanations and who consent in writing
Exclusion Criteria:
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Those with a history of severe hypersensitivity to the investigational product or combination anticancer drugs.
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Those with the following medical history or surgical history/procedural history confirmed
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Other primary malignant tumors other than pancreatic cancer
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Major surgery that requires general anesthesia or breathing aid
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Severe cardiovascular disease
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New York Heart Association Class 3 or 4 heart failure
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Severe cerebrovascular disease t
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Pulmonary thrombosis, deep vein thrombosis, or bronchial asthma, obstructive pulmonary disease, and other life-threatening severe lung diseases
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Infections requiring administration of systemic antibiotics or antivirals, etc.
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Hematologic malignancy
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Those with the following diseases
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Massive ascites, pleural effusions requiring therapeutic paracentesis
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Neuropathy ≥Grade 2
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Diarrhea, chronic inflammatory bowel disease
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Intestinal paralysis, intestinal obstruction
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Diseases that make oral administration difficult or affect absorption
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Interstitial lung disease, pulmonary fibrosis
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Dialysis patient
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Patients with clinically significant symptoms or uncontrolled central nervous system or brain metastases
- 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
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Those with a medication history of the following drugs
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Anti-cancer drug therapy such as chemotherapy and biological therapy
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Radiation therapy within 2 weeks of baseline
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Those who are taking or expected to require administration of strong inhibitors or inducers of CYP3A4
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(For mFOLFIRINOX cohort) Those who are taking or expected to require administration of sorivudine
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Patients who require continuous administration of non-steroidal anti-inflammatory drugs (NSAIDs) with high bleeding risk
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Patients requiring continuous administration of systemic corticosteroid equivalent to prednisone >10 mg/day
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Those who have received antithrombotic agents, including antiplatelet agents, anticoagulants, etc.
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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
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Those who have administered other investigational products or have received investigational medical device procedures within 4 weeks of the baseline
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Other patients who are inappropriate or unable to participate in this clinical study at the discretion of the investigator
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Onconic Therapeutics Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- JPI-547-102