Clinical trial NCT02697058: Phase II of BAX2398/5-FU/Calcium Levofolinate in Pancreatic Cancer
Official title: Phase II Randomized Study of BAX2398 in Combination With 5-Fluorouracil and Calcium Levofolinate in Japanese Patients With Metastatic Pancreatic Cancer, Which Progressed or Recurred After Prior Gemcitabine-Based Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Pancreatic Cancer
Lead sponsor: Servier
Sponsor class: INDUSTRY
Collaborators: name: ADIR, a Servier Group company
First posted: 2016-03-03
Enrollment: 84
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: Study Part 1: To assess the safety and tolerability, and to characterize the pharmacokinetics (PK) of BAX2398 in combination with 5-FU/calcium levofolinate in Japanese patients.

Study Part 2: To compare the efficacy of BAX2398 in combination with 5-FU/calcium levofolinate versus 5-FU/calcium levofolinate as assessed by Progression Free Survival (PFS) using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).


Eligibility criteria: Inclusion Criteria:

1. Participant is ≥20 years of age at the time of screening.
2. Histologically or cytologically confirmed adenocarcinoma of exocrine pancreas
3. Documented metastatic disease
4. Metastatic disease with at least one measurable lesion as defined by RECIST 1.1 guidelines
5. Documented disease progression after prior gemcitabine or any gemcitabine containing therapy but excluding irinotecan, for locally advanced or metastatic setting. Prior chemotherapy must be stopped for at least 21 days before the first dose.
6. Karnofsky Performance Status (KPS) ≥70
7. Adequate bone marrow reserves
8. Adequate hepatic function
9. Adequate renal function
10. Normal ECG including Fridericia corrected QT interval (QTcF) \<440 ms within 7 days prior to first dose of study drug
11. Recovered from the effects of any prior surgery, radiotherapy or other anti-neoplastic therapy with no residual adverse events (AEs) of Grade ≥2.
12. Able to understand and sign an informed consent (or have a legal representative who is able to do so)
13. If female of childbearing potential, participant presents with a negative pregnancy, and agrees to employ adequate birth control measures during the study dosing period and for 3 months following the last dose of study drug.
14. Participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

1. Active and uncontrolled central nervous system (CNS) metastases; for controlled CNS metastases, patient should have been off steroids for at least 28 days prior to starting study therapy.
2. History of any second malignancy in the last 5 years; participants with prior history of in-situ cancer or basal or squamous cell skin cancers are eligible. Participants with other malignancies are eligible if they have been continuously disease free for at least 5 years.
3. Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before inclusion.
4. Cannot stop medications that are potent CYP3A4 inducers within 2 weeks and inhibitors within 1 week before start of treatment.
5. Significant cardiac conduction abnormalities, including a history of long QTcF syndrome and/or pacemaker.
6. New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure.
7. Active infection, including active hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV, or an unexplained fever \>38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, patients with tumor fever may be enrolled), which in the investigator's opinion might compromise the patient's participation in the trial or affect the study outcome.
8. Known hypersensitivity to any of the components of BAX2398, other liposomal products, fluoropyrimidines, or calcium levofolinate.
9. Any other medical or social condition deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
10. Participant has been exposed to an investigational product (IP) within 30 days prior to the first dose of the study drug or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
11. Participant is a family member or employee of the investigator.
12. Participant is pregnant or lactating at the time of enrollment. Lactating mothers can resume breast feeding 30 days following the last dose of the study treatment.

Primary outcomes:
measure: Progression Free Survival (PFS) in Part 2 of Study
timeFrame: Part 2 Baseline to the end of the study (up to 22 months)
Secondary outcomes:
measure: Progression Free Survival (PFS) in Part 1 of Study
timeFrame: Part 1 Baseline to the end of the study (up to 22 months)
measure: Overall Survival (OS)
timeFrame: Baseline to the end of the study (up to 22 months)
measure: Time to Treatment Failure (TTF)
timeFrame: Baseline to the end of the study (up to 22 months)
measure: Objective Response Rate (ORR)
timeFrame: Baseline to the end of the study (up to 22 months)
measure: Disease Control Rate (DCR)
timeFrame: Baseline to the end of the study (up to 22 months)
measure: Tumor Marker Response
timeFrame: Baseline, every 6 weeks and 37 days post last visit (up to 22 months)
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores
timeFrame: Baseline, Day 1 of Cycle 4, 7, 10, 13, and 16; and 37 days post last visit (up to 22 months)
measure: Change From Baseline in Pain
timeFrame: Baseline, Days 1 and 8 of Cycles 1, 2, 4, 5, 7, 8, 10, 11, 13, 14, 16, 17, Day 1 of Cycles 3, 6, 9, 12, 15, 18 and 37 days post last visit (up to 22 months)
measure: Change from Baseline in Analgesic use
timeFrame: Baseline, Days 1 and 8 of Cycles 1, 2, 4, 5, 7, 8, 10, 11, 13, 14, 16, 17, Day 1 of Cycles 3, 6, 9, 12, 15, 18 and 37 days post last visit (up to 22 months)
measure: Number of Participants With Karnofsky Performance Score (KPS)
timeFrame: Baseline, Day 1 of Cycles 1 - 18 and 37 days post last visit (up to 22 months)
measure: Change From Baseline in Weight
timeFrame: Baseline, Days 1 and 8 of Cycles 1, 2, 4, 5, 7, 8, 10, 11, 13, 14, 16, 17, Day 1 of Cycles 3, 6, 9, 12, 15, 18 and 37 days post last visit (up to 22 months)
measure: Number of Participants With Serious Adverse Events
timeFrame: From start of study treatment up to 22 months
measure: Number of Participants With Non-Serious Adverse Events
timeFrame: From start of study treatment up to 22 months
measure: Number of Participants With Clinically Significant Findings From the Physical Examination
timeFrame: From start of study treatment up to 22 months
measure: Number of Participants With Clinically Significant Changes in Vital Signs
timeFrame: From start of study treatment up to 22 months
measure: Number of Participants With Clinically Significant Changes in Laboratory Results
timeFrame: From start of study treatment up to 22 months
measure: Number of Participants With Clinically Significant Changes in Twelve-lead Electrocardiogram (ECG)
timeFrame: From start of study treatment up to 22 months
measure: Maximum Plasma Concentration (Cmax) of Total Irinotecan in Study Part 1
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Maximum Plasma Concentration (Cmax) of Total Primary Metabolite of Irinotecan (SN-38) in Study Part 1
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Maximum Plasma Concentration (Cmax) of SN-38-Glucuronide (SN-38G) in Study Part 1
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Time of Maximum Concentration (tmax) of Total Irinotecan, Total SN-38, and SN-38-Glucuronide (SN-38G) in Study Part 1
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Terminal Half-Life (t1/2) of Total Irinotecan, Total SN-38, and SN-38-Glucuronide (SN-38G) in Study Part 1
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) of Total Irinotecan in Study Part 1
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) of Total SN-38 in Study Part 1.
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) of SN-38-Glucuronide (SN-38G) IN Study Part 1.
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Systemic Clearance (CL) of Total Irinotecan in Study Part 1
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Systemic Clearance (CL) of Total SN-38 in Study Part 1
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Systemic Clearance (CL) of SN-38-Glucuronide (SN-38G) in Study Part 1
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Volume of Distribution (V) of Total Irinotecan in Study Part 1
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Volume of Distribution (V) of Total SN-38 in Study Part 1.
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Volume of Distribution (V) of SN-38-Glucuronide (SN-38G) in Study Part 1.
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Volume of Distribution at Steady-State (Vss) of Total Irinotecan in Study Part 1
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Volume of Distribution at Steady-state (Vss) of Total SN-38 in Study Part 1
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Volume of Distribution at Steady-state (Vss) of SN-38-Glucuronide (SN-38G) in Study Part 1
timeFrame: Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose
measure: Terminal Half-life (t1/2) - Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)
timeFrame: Cycle 1: pre dose, 15-90 minutes after start of infusion; and 0-6, 6-24, 24-48, 72-168, and 216-264 hours after the end of the infusion; Cycle 2: pre dose
measure: Area Under the Curve (AUC) - Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)
timeFrame: Cycle 1: pre dose, 15-90 minutes after start of infusion; and 0-6, 6-24, 24-48, 72-168, and 216-264 hours after the end of the infusion; Cycle 2: pre dose
measure: Systemic Clearance (CL) -Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)
timeFrame: Cycle 1: pre dose, 15-90 minutes after start of infusion; and 0-6, 6-24, 24-48, 72-168, and 216-264 hours after the end of the infusion; Cycle 2: pre dose
measure: Volume of Distribution (V)-Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)
timeFrame: Cycle 1: pre dose, 15-90 minutes after start of infusion; and 0-6, 6-24, 24-48, 72-168, and 216-264 hours after the end of the infusion; Cycle 2: pre dose
measure: Volume of Distribution at Steady-State (Vss)-Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)
timeFrame: Cycle 1: pre dose, 15-90 minutes after start of infusion; and 0-6, 6-24, 24-48, 72-168, and 216-264 hours after the end of the infusion; Cycle 2: pre dose
Other outcomes:
Locations:
city: Hirosaki-shi
country: Japan
facility: Hirosaki University School of Medicine & Hospital
state: Aomori-Ken
city: Chiba-shi
country: Japan
facility: Chiba Cancer Center
state: Chiba-Ken
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba-Ken
city: Matsuyama-shi
country: Japan
facility: NHO Shikoku Cancer Center
state: Ehime-Ken
city: Fukuoka-shi
country: Japan
facility: NHO Kyushu Cancer Center
state: Fukuoka-Ken
city: Fukuoka-shi
country: Japan
facility: Kyushu University Hospital
state: Fukuoka-Ken
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa -ku
city: Yokohama-shi
country: Japan
facility: Yokohama City University Medical Center
state: Kanagawa-Ken
city: Kyoto-shi
country: Japan
facility: Kyoto University Hospital
state: Kyoto-Fu
city: Osaka-shi
country: Japan
facility: NHO Osaka National Hospital
state: Osaka-Fu
city: Osaka-shi
country: Japan
facility: Osaka International Cancer Institute
state: Osaka-Fu
city: Kitaadachi-gun
country: Japan
facility: Saitama Cancer Center
state: Saitama-Ken
city: Koto-ku
country: Japan
facility: Cancer Institute Hospital of JFCR
state: Tokyo-To
city: Mitaka-shi
country: Japan
facility: Kyorin University Hospital
state: Tokyo-To
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
Study officials:
References:
citation: Ueno M, Nakamori S, Sugimori K, Kanai M, Ikeda M, Ozaka M, Furukawa M, Okusaka T, Kawabe K, Furuse J, Komatsu Y, Ishii H, Sato A, Shimizu S, Chugh P, Tang R, Ioka T. nal-IRI+5-FU/LV versus 5-FU/LV in post-gemcitabine metastatic pancreatic cancer: Randomized phase 2 trial in Japanese patients. Cancer Med. 2020 Dec;9(24):9396-9408. doi: 10.1002/cam4.3558. Epub 2020 Oct 25.