Metastatic Pancreatic CancerPhase 2NCT02697058
Phase II of BAX2398/5-FU/Calcium Levofolinate in Pancreatic Cancer
A Phase 2 study testing BAX2398 + 5-FU/calcium levofolinate and 5-FU/calcium levofolinate in people with Metastatic Pancreatic Cancer, run by Institut de Recherches Internationales Servier at 16 sites in Japan.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Metastatic Pancreatic Cancer
- What is being tested?
- BAX2398 + 5-FU/calcium levofolinate and 5-FU/calcium levofolinate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 16 sitesJapan
- Study dates
- 30 Mar 2016to 28 Aug 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant is ≥20 years of age at the time of screening.
- Histologically or cytologically confirmed adenocarcinoma of exocrine pancreas
- Documented metastatic disease
- Metastatic disease with at least one measurable lesion as defined by RECIST 1.1 guidelines
- 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.
- Karnofsky Performance Status (KPS) ≥70
Show all 14Show fewer
- Adequate bone marrow reserves
- Adequate hepatic function
- Adequate renal function
- Normal ECG including Fridericia corrected QT interval (QTcF) <440 ms within 7 days prior to first dose of study drug
- Recovered from the effects of any prior surgery, radiotherapy or other anti-neoplastic therapy with no residual adverse events (AEs) of Grade ≥2.
- Able to understand and sign an informed consent (or have a legal representative who is able to do so)
- 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.
- Participant is willing and able to comply with the requirements of the protocol.
Who cannot join
- 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.
- 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.
- Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before inclusion.
- Cannot stop medications that are potent CYP3A4 inducers within 2 weeks and inhibitors within 1 week before start of treatment.
- Significant cardiac conduction abnormalities, including a history of long QTcF syndrome and/or pacemaker.
- New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure.
Show all 12Show fewer
- 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.
- Known hypersensitivity to any of the components of BAX2398, other liposomal products, fluoropyrimidines, or calcium levofolinate.
- 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.
- 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.
- Participant is a family member or employee of the investigator.
- 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.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
Japan16 sites
Chiba Cancer Center
Chiba, Chiba, 260-8717
National Cancer Center Hospital
Chuo Ku, Tokyo, 104-0045
NHO Kyushu Cancer Center
Fukuoka, Fukuoka, 811-1395
Kyushu University Hospital
Fukuoka, Fukuoka, 812-8582
Hirosaki University School of Medicine & Hospital
Hirosaki-shi, Aomori, 036-8563
National Cancer Center Hospital East
Kashiwa-shi, Chiba, 277-8577
Saitama Cancer Center
Kitaadachi-gun, Saitama, 362-0806
Cancer Institute Hospital of JFCR
Kōtoku, Tokyo-To, 135-8550
Kyoto University Hospital
Kyoto, Kyoto, 606-8507
NHO Shikoku Cancer Center
Matsuyama, Ehime, 791-0280
Kyorin University Hospital
Mitaka-shi, Tokyo-To, 181-8611
NHO Osaka National Hospital
Osaka, Osaka, 540-0006
Osaka International Cancer Institute
Osaka, Osaka, 541-8567
Hokkaido University Hospital
Sapporo, Hokkaido, 060-8648
Yokohama City University Medical Center
Yokohama, Kanagawa, 232-0024
Kanagawa Cancer Center
Yokohama, Kanagawa -ku, 241-8515
About this study
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 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).
- Conditions
- Metastatic Pancreatic Cancer
- Being tested
- BAX2398 + 5-FU/calcium levofolinate, 5-FU/calcium levofolinate
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAX2398 + 5-FU/calcium levofolinateBiological
Also called nal-IRI, MM-398
BAX2398 (a liposomal formulation of irinotecan) in combination with 5-FU/calcium levofolinate
5-FU/calcium levofolinateDrug
5-FU/calcium levofolinate alone
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Safety and PK | Experimental | BAX2398 in combination with 5-FU/calcium levofolinate Receives: Biological: BAX2398 + 5-FU/calcium levofolinate |
| Part 2: Safety, PK, Efficacy | Experimental | BAX2398 in combination with 5-FU/calcium levofolinate Receives: Biological: BAX2398 + 5-FU/calcium levofolinate |
| Part 2: 5-FU/calcium levofolinate alone | Active comparator | 5-FU/calcium levofolinate Receives: Drug: 5-FU/calcium levofolinate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS) in Part 2 of Study
Progression Free Survival (PFS) was defined as the time from randomization to the first documented disease progression based on the independent central review board's assessment using RECIST 1.1 or death due to any cause, whichever occurred first.
Measured: Part 2 Baseline to the end of the study (up to 22 months)
Secondary outcomes (39)
Progression Free Survival (PFS) in Part 1 of Study
Progression Free Survival (PFS) was defined as the time from randomization to the first documented disease progression based on the independent central review board's assessment using RECIST 1.1 or death due to any cause, whichever occurred first.
Measured: Part 1 Baseline to the end of the study (up to 22 months)
Overall Survival (OS)
OS was defined as the time from the date of informed consent (Part 1) or date of randomization (Part 2) to death due to any cause or the date of last known alive.
Measured: Baseline to the end of the study (up to 22 months)
Time to Treatment Failure (TTF)
TTF was defined as the time from randomization to disease progression according to RECIST 1.1, death due to any cause, discontinuation of treatment due to toxicity, or for symptomatic deterioration, or start of another anticancer therapy
Measured: Baseline to the end of the study (up to 22 months)
Objective Response Rate (ORR)
ORR was defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR)
Measured: Baseline to the end of the study (up to 22 months)
Disease Control Rate (DCR)
DCR was defined as the proportion of participants with a best overall response of complete response (CR); partial response (PR); or stable disease (SD) lasting >=24 weeks
Measured: Baseline to the end of the study (up to 22 months)
Tumor Marker Response
Tumor marker response was defined as decrease of 50% of cancer antigen (CA)-19-9 in relation to the baseline level at least once during the treatment period. Tumor marker response evaluable population consist of participants who have elevated CA-19-9 level (greater than [<] 30 international unit [IU] / millilitre [ml]) at baseline and at least one post baseline CA-19-9 assessment.
Measured: Baseline, every 6 weeks and 37 days post last visit (up to 22 months)
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores
The EORTC-QLQC30 is a reliable and valid measure of the quality of life of cancer participants in multicultural clinical research settings. It incorporates nine multi-item scales: five functional scales (physical [PFS], role [RFS], cognitive [CFS], emotional [EFS], and social [SFS]); three symptom scales (fatigue [FSS], pain [PSS], and nausea and vomiting [NVSS]); and a global health status (GHS) and quality-of-life scale. Several single-item symptom measures are also included. All scales and single-item measures range=0 to 100. High score for a functional scale=high/healthy level of functioning. High score for global health status/QoL=high QoL. High score for symptom scale/single item=high level of symptomatology/problems.
Measured: Baseline, Day 1 of Cycle 4, 7, 10, 13, and 16; and 37 days post last visit (up to 22 months)
Change From Baseline in Pain
Participants assessed pain on the VAS. VAS range: 0 (no pain) to 100 worst pain.
Measured: 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)
Change from Baseline in Analgesic use
Participants recorded their analgesic usage in diaries.
Measured: 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)
Number of Participants With Karnofsky Performance Score (KPS)
The Karnofsky score runs from 100 to 0, where 100 is "perfect" health and 0 is death.
Measured: Baseline, Day 1 of Cycles 1 - 18 and 37 days post last visit (up to 22 months)
Change From Baseline in Weight
The participant defined to be a clinical benefit responder if the weight change is classified as Positive. (1) Positive: an increase of at least 7% over baseline, maintained for at least 2 cycles (2) Non-positive: any other change in weight.
Measured: 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)
Number of Participants With Serious Adverse Events
A Serious adverse event (AE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Measured: From start of study treatment up to 22 months
Number of Participants With Non-Serious Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.
Measured: From start of study treatment up to 22 months
Number of Participants With Clinically Significant Findings From the Physical Examination
Physical examination done on the following body systems: general appearance, head and neck, eyes and ears, nose and throat, chest, lungs, heart, abdomen, extremities and joints, lymph nodes, skin, and neurological.
Measured: From start of study treatment up to 22 months
Number of Participants With Clinically Significant Changes in Vital Signs
Number of participants with clinically significant changes in vital signs assessed by measuring height, weight, temperature, respiration rate, pulse rate, systolic and diastolic blood pressure, and body surface area at all the listed time points was reported.
Measured: From start of study treatment up to 22 months
Number of Participants With Clinically Significant Changes in Laboratory Results
Number of participants with clinically significant changes in laboratory results was reported.
Measured: From start of study treatment up to 22 months
Number of Participants With Clinically Significant Changes in Twelve-lead Electrocardiogram (ECG)
Number of participants with clinically significant changes in ECG results was reported.
Measured: From start of study treatment up to 22 months
Maximum Plasma Concentration (Cmax) of Total Irinotecan in Study Part 1
The Cmax of total irinotecan (encapsulated + unencapsulated) in study part 1 was reported.
Measured: 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
Maximum Plasma Concentration (Cmax) of Total Primary Metabolite of Irinotecan (SN-38) in Study Part 1
The Cmax of total SN-38 (encapsulated + unencapsulated) in study part 1 was reported.
Measured: 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
Maximum Plasma Concentration (Cmax) of SN-38-Glucuronide (SN-38G) in Study Part 1
The Cmax of SN-38G in study part 1 was reported.
Measured: 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
Time of Maximum Concentration (tmax) of Total Irinotecan, Total SN-38, and SN-38-Glucuronide (SN-38G) in Study Part 1
The Tmax of total irinotecan (encapsulated + unencapsulated), total SN-38 (encapsulated + unencapsulated), and SN-38G was reported.
Measured: 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
Terminal Half-Life (t1/2) of Total Irinotecan, Total SN-38, and SN-38-Glucuronide (SN-38G) in Study Part 1
The t1/2 of Total irinotecan (encapsulated + unencapsulated), total SN-38 (encapsulated + unencapsulated), and SN-38-glucuronide (SN-38G) in study part 1 was reported.
Measured: 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
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
The AUC0-infinity of Total irinotecan (encapsulated + unencapsulated) in study part 1 was reported.
Measured: 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
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.
The AUC0-infinity of total SN-38 (encapsulated + unencapsulated)in study part 1 was reported.
Measured: 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
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.
The AUC0-infinity of SN-38-glucuronide (SN-38G) in study part 1 was reported.
Measured: 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
Systemic Clearance (CL) of Total Irinotecan in Study Part 1
The CL of total irinotecan (encapsulated + unencapsulated) in study part 1 was reported.
Measured: 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
Systemic Clearance (CL) of Total SN-38 in Study Part 1
The CL of SN-38 (encapsulated + unencapsulated), in study part 1 was reported.
Measured: 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
Systemic Clearance (CL) of SN-38-Glucuronide (SN-38G) in Study Part 1
The CL of SN-38-glucuronide (SN-38G) in study part 1 was reported.
Measured: 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
Volume of Distribution (V) of Total Irinotecan in Study Part 1
The V of total irinotecan (encapsulated + unencapsulated) in study part 1 was reported.
Measured: 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
Volume of Distribution (V) of Total SN-38 in Study Part 1.
The V of total SN-38 (encapsulated + unencapsulated), in study part 1 was reported.
Measured: 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
Volume of Distribution (V) of SN-38-Glucuronide (SN-38G) in Study Part 1.
The V of SN-38-glucuronide (SN-38G) in study part 1 was reported.
Measured: 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
Volume of Distribution at Steady-State (Vss) of Total Irinotecan in Study Part 1
The Vss of total irinotecan (encapsulated + unencapsulated) in study part 1 was reported.
Measured: 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
Volume of Distribution at Steady-state (Vss) of Total SN-38 in Study Part 1
The Vss of total irinotecan (encapsulated + unencapsulated), SN-38 (encapsulated + unencapsulated), and SN-38-glucuronide (SN-38G) was reported.
Measured: 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
Volume of Distribution at Steady-state (Vss) of SN-38-Glucuronide (SN-38G) in Study Part 1
The Vss of SN-38-glucuronide (SN-38G) in study part 1 was reported.
Measured: 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
Terminal Half-life (t1/2) - Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)
The t1/2 of total irinotecan (encapsulated + unencapsulated), SN-38 (encapsulated + unencapsulated), and SN-38-glucuronide (SN-38G) was reported.
Measured: 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
Area Under the Curve (AUC) - Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)
The AUC of total irinotecan (encapsulated + unencapsulated), SN-38 (encapsulated + unencapsulated), and SN-38-glucuronide (SN-38G) was reported.
Measured: 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
Systemic Clearance (CL) -Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)
The CL of total irinotecan (encapsulated + unencapsulated), SN-38 (encapsulated + unencapsulated), and SN-38-glucuronide (SN-38G) was reported.
Measured: 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
Volume of Distribution (V)-Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)
The V of total irinotecan (encapsulated + unencapsulated), SN-38 (encapsulated + unencapsulated), and SN-38-glucuronide (SN-38G) was reported.
Measured: 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
Volume of Distribution at Steady-State (Vss)-Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)
The Vss of total irinotecan (encapsulated + unencapsulated), SN-38 (encapsulated + unencapsulated), and SN-38-glucuronide (SN-38G) was reported.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2016 (estimated)
- Study start30 Mar 2016
- Primary completion4 May 2017
- Study completion28 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut de Recherches Internationales Servier
- Sponsor type
- University, hospital or other
- Collaborators
- ADIR, a Servier Group company
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02697058
- Sponsor's protocol ID
- 331501
- Status last verified
- Jul 2024
- First submitted
- 20 Feb 2016
- Last updated
- 25 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. They can ask for all interventional clinical studies: * submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.
Publications
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.
PubMed 33099898
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02697058
- Acronym / sponsor ID
- 331501
- Conditions
- Metastatic Pancreatic Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Institut de Recherches Internationales ServierUniversity, hospital or other
- Collaborators
- ADIR, a Servier Group company
- Study start
- 30 Mar 2016 (actual)
- Primary completion
- 4 May 2017 (actual)
- Study completion
- 28 Aug 2018 (actual)
- First posted
- 3 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1: Safety and PK | Experimental | Biological: BAX2398 + 5-FU/calcium levofolinateBAX2398 in combination with 5-FU/calcium levofolinate |
| Part 2: Safety, PK, Efficacy | Experimental | Biological: BAX2398 + 5-FU/calcium levofolinateBAX2398 in combination with 5-FU/calcium levofolinate |
| Part 2: 5-FU/calcium levofolinate alone | Active comparator | Drug: 5-FU/calcium levofolinate5-FU/calcium levofolinate |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Participant is ≥20 years of age at the time of screening.
- Histologically or cytologically confirmed adenocarcinoma of exocrine pancreas
- Documented metastatic disease
- Metastatic disease with at least one measurable lesion as defined by RECIST 1.1 guidelines
- 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.
Key exclusion criteria (12 listed)
- 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.
- 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.
- Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before inclusion.
- Cannot stop medications that are potent CYP3A4 inducers within 2 weeks and inhibitors within 1 week before start of treatment.
- Significant cardiac conduction abnormalities, including a history of long QTcF syndrome and/or pacemaker.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BAX2398 + 5-FU/calcium levofolinateAlso: nal-IRI, MM-398BAX2398 (a liposomal formulation of irinotecan) in combination with 5-FU/calcium levofolinate | Biological | Part 1: Safety and PK, Part 2: Safety, PK, Efficacy |
| 5-FU/calcium levofolinate5-FU/calcium levofolinate alone | Drug | Part 2: 5-FU/calcium levofolinate alone |
Primary outcome
Progression Free Survival (PFS) in Part 2 of Study
Time frame: Part 2 Baseline to the end of the study (up to 22 months)
Progression Free Survival (PFS) was defined as the time from randomization to the first documented disease progression based on the independent central review board's assessment using RECIST 1.1 or death due to any cause, whichever occurred first.
39 secondary outcomes
Progression Free Survival (PFS) in Part 1 of Study
Time frame: Part 1 Baseline to the end of the study (up to 22 months)
Overall Survival (OS)
Time frame: Baseline to the end of the study (up to 22 months)
Time to Treatment Failure (TTF)
Time frame: Baseline to the end of the study (up to 22 months)
Objective Response Rate (ORR)
Time frame: Baseline to the end of the study (up to 22 months)
Disease Control Rate (DCR)
Time frame: Baseline to the end of the study (up to 22 months)
Tumor Marker Response
Time frame: Baseline, every 6 weeks and 37 days post last visit (up to 22 months)
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores
Time frame: Baseline, Day 1 of Cycle 4, 7, 10, 13, and 16; and 37 days post last visit (up to 22 months)
Change From Baseline in Pain
Time frame: 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)
Change from Baseline in Analgesic use
Time frame: 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)
Number of Participants With Karnofsky Performance Score (KPS)
Time frame: Baseline, Day 1 of Cycles 1 - 18 and 37 days post last visit (up to 22 months)
Change From Baseline in Weight
Time frame: 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)
Number of Participants With Serious Adverse Events
Time frame: From start of study treatment up to 22 months
Number of Participants With Non-Serious Adverse Events
Time frame: From start of study treatment up to 22 months
Number of Participants With Clinically Significant Findings From the Physical Examination
Time frame: From start of study treatment up to 22 months
Number of Participants With Clinically Significant Changes in Vital Signs
Time frame: From start of study treatment up to 22 months
Number of Participants With Clinically Significant Changes in Laboratory Results
Time frame: From start of study treatment up to 22 months
Number of Participants With Clinically Significant Changes in Twelve-lead Electrocardiogram (ECG)
Time frame: From start of study treatment up to 22 months
Maximum Plasma Concentration (Cmax) of Total Irinotecan in Study Part 1
Time frame: 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
Maximum Plasma Concentration (Cmax) of Total Primary Metabolite of Irinotecan (SN-38) in Study Part 1
Time frame: 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
Maximum Plasma Concentration (Cmax) of SN-38-Glucuronide (SN-38G) in Study Part 1
Time frame: 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
Time of Maximum Concentration (tmax) of Total Irinotecan, Total SN-38, and SN-38-Glucuronide (SN-38G) in Study Part 1
Time frame: 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
Terminal Half-Life (t1/2) of Total Irinotecan, Total SN-38, and SN-38-Glucuronide (SN-38G) in Study Part 1
Time frame: 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
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
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
Systemic Clearance (CL) of Total Irinotecan in Study Part 1
Time frame: 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
Systemic Clearance (CL) of Total SN-38 in Study Part 1
Time frame: 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
Systemic Clearance (CL) of SN-38-Glucuronide (SN-38G) in Study Part 1
Time frame: 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
Volume of Distribution (V) of Total Irinotecan in Study Part 1
Time frame: 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
Volume of Distribution (V) of Total SN-38 in Study Part 1.
Time frame: 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
Volume of Distribution (V) of SN-38-Glucuronide (SN-38G) in Study Part 1.
Time frame: 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
Volume of Distribution at Steady-State (Vss) of Total Irinotecan in Study Part 1
Time frame: 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
Volume of Distribution at Steady-state (Vss) of Total SN-38 in Study Part 1
Time frame: 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
Volume of Distribution at Steady-state (Vss) of SN-38-Glucuronide (SN-38G) in Study Part 1
Time frame: 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
Terminal Half-life (t1/2) - Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)
Time frame: 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
Area Under the Curve (AUC) - Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)
Time frame: 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
Systemic Clearance (CL) -Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)
Time frame: 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
Volume of Distribution (V)-Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)
Time frame: 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
Volume of Distribution at Steady-State (Vss)-Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2024.
- Background: PubMed 33099898Ueno 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.
- Individual participant dataSharing planned: Yes. Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. They can ask for all interventional clinical studies: * submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.
Related trials for Metastatic Pancreatic Cancer
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
RecruitingPhase 1
Modified FOLFIRINOX and Pentamidine in Advanced and Metastatic Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma (PDAC)
RecruitingPhase 3
Atebimetinib + GnP as a First Line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma
Pancreatic Cancer, Pancreatic Cancer Metastatic
RecruitingPhase 3
Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma ( RASolute 305 )
Pancreatic Cancer, Pancreatic Cancer Metastatic
Recruiting
CREO - Microwave Ablation Feasibility Study
Pancreatic Cancer, Liver Cancer (Locally Advanced or Metastatic)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BAX2398 + 5-FU/calcium levofolinate and 5-FU/calcium levofolinate in people with Metastatic Pancreatic Cancer, run by Institut de Recherches Internationales Servier at 16 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) in Part 2 of Study (time frame: Part 2 Baseline to the end of the study (up to 22 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02697058, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2024.