Carcinoma, Pancreatic DuctalPhase 2NCT03403101
The Combination Chemotherapy of SIRIOX as First- or Second-Line Chemotherapy for Pancreatic Cancer
A Phase 2 study testing S1, Oxaliplatin and Irinotecan in people with Carcinoma, Pancreatic Ductal, run by Fudan University at 2 sites in China.
Trial summary
Pancreatic cancer represents the most lethal of the common malignancies with a 5-year survival rate of less than 5%. For patients who are eligible for potentially curative resection, despite mortality and morbidity rates after surgery have improved, the recurrence rate is up to 85% within 2 years. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Carcinoma, Pancreatic Ductal
- What is being tested?
- S1, Oxaliplatin and Irinotecan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 2 sitesChina
- Study dates
- 1 Jul 2020to 1 Jul 2024
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged 18 - 75 years old at the time of signing the ICF.
- Patients with pathologically proved adenocarcinoma of pancreatic cancer and diagnosed with inoperable/metastatic disease (previous systemic chemotherapy, neoadjuvant or adjuvant are acceptable without Irinotecan, Oxaliplatin, or S1).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Adequate hematologic function defined as: absolute neutrophil count (ANC) >= 2,000/μL; platelets count >= 100,000/μL; hemoglobin must be >= 10 g/dL (can be corrected by growth factor or transfusion).
- Adequate hepatic function defined as: serum bilirubin =< 1.5-fold upper limit of normal (ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) =< 3-fold ULN (5-fold ULN if liver metastasis is observed).
- Adequate renal function with: serum creatinine =< 1.3 mg/dL or calculated creatinine clearance >= 60 mL/minute according to the Cockcroft and Gault formula.
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- At least one measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Life expectancy over 12 weeks.
- Women must be either of non-child bearing potential, or women with child-bearing potential agree to use effective a highly contraceptive method or a contraceptive implant, exception of hormonal contraception (estrogen/progesterone), during treatment from time of Screening Visit and after cessation of therapy at least 3 months.
- Willing and able to comply with all aspects of the treatment protocol.
- Provide written informed consent.
Who cannot join
- Patients who are unwilling or unable to comply with the study protocol;
- Existing anticancer treatment-related toxicities of Grades >= 2 (except for alopecia and neuropathy) according to Common Terminology Criteria for Adverse Events (CTCAE v4.03).
- Simultaneously using targeted therapies, such as Erlotinib, Nimotuzumab etc;
- Any severe or uncontrolled systemic disease (e.g., unstable or decompensated breathing, heart, liver or kidney disease, HIV infection, hypertension, severe arrhythmia, diabetes mellitus, massive active bleeding);
- Large operations were performed within 14 days before entering the study, or there were surgical incisions that were not completely healed;
- Women who are pregnant or breastfeeding;
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- Ascertained hypersensitivity to investigational product, Oxaliplatin, Irinotecan, and S1 or any of the excipients used in the study.
- History of other malignancies within 5 years, except for adequately treated basal cell carcinoma or squamous cell carcinoma or carcinoma in situ;
- Obvious gastrointestinal injury history, the researchers estimate may significantly affect the absorption of S1 on the whole, including the ability to swallow drugs;
- Other combinations of anticancer therapies (including LHRH agonists, anticancer herbs, immunotherapy), except steroid hormones;
- Patients with UGT1A1 mutations or congenital disease lack of UGT1A1 expression (e.g. Crigler-Najjar syndrome and Gilbert syndrome);
- Patients with DPD enzyme deficiency.
- Judged to be not applicable to this study by investigator such as difficulty of follow-up observation, psychiatric disorder, with any other serious diseases/medical history.
Trial locations and contacts
2 sites in 1 country.
China2 sites, 2 recruiting
- Recruiting
Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University
Shanghai, Shanghai Municipality, 200032
Xianjun Yu, M.D., Ph.D., +86 21 64175590, yuxianjun@fudanpci.org
- Recruiting
Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University; 270 Dong An Road, Shanghai 200032, China
Shanghai, 200032
Xian-Jun Yu, M.D., Ph.D., +86-21-64175590, yuxianjun@fudanpci.org
Wen-Quan Wang, M.D., Ph.D., +86-21-64175590, wangwenquan@fudanpci.org
About this study
Official title: A Phase II, Single Arm, Open Label Study to Evaluate the Efficacy and Safety of the Combination of S-1, Irinotecan and Oxaliplatin (SIRIOX) in Treating Patients With Advanced Inoperable or Metastatic Pancreatic Cancer
Pancreatic cancer represents the most lethal of the common malignancies with a 5-year survival rate of less than 5%. For patients who are eligible for potentially curative resection, despite mortality and morbidity rates after surgery have improved, the recurrence rate is up to 85% within 2 years. FOLFIRINOX (fluoropyrimidine/leucovorin plus irinotecan and oxaliplatin) has been proved to significantly improve the prognosis and is recommended as first line treatment in patients with advanced pancreatic cancer. However, the regimen is limited due to the severe adverse effects. Thus, the investigators replaced 5-FU and leucovorin in the FOLFIRINOX regimen with oral S-1, a new oral fluoropyrimidine derivative which was proved to be the well-tolerated and effectively in large III phase randomized clinical trial, to form the SIRIOX regimen. A phase I clinical trial from Japan found that SOXIRI (S-1, oxaliplatin and irinotecan) works in patients with advanced pancreatic cancer. In this study, the researchers intend to investigate the activity and safety of the combination of this regimen in patients with advanced pancreatic cancer, as first- or second-line chemotherapy.
Read the detailed description
Pancreatic cancer (mainly pancreatic ductal adenocarcinoma, PDAC) is a disease with extremely poor prognosis, and is often fatal. Surgical resection is the only potentially curative technique for management of PDAC, but only approximately 15% to 20% of patients are candidates for pancreatectomy at the time of diagnosis Gemcitabine (Gem) is widely used as a standard chemotherapeutic agent for advanced pancreatic cancer. FOLFIRINOX (fluoropyrimidine/leucovorin plus irinotecan and oxaliplatin), compared with Gem, has been proved to significantly improve the objective response rate (31.6% VS. 9.4%, P < 0.001) and prolong the median survival time (11.1 months VS. 6.8 months, P < 0.001) for patients with metastatic pancreatic ductal adenocarcinoma(PDAC), who had a performance status of ECOG 0-1 score. However, it is undeniable that the adverse effects of FOLFIRINOX are severe. For example, the incidence of 3/4 grade neutrophil decrease in patients receiving FOLFIRINOX is significantly higher than those with Gem (45.7% VS. 21%, P < 0.001). Thus, it is difficult for many patients to receive standard FOLFIRINOX and benefit from the protocol. Therefore, the investigators aim to explore an improvement program of FOLFIRINOX, hoping to better benefit patients.
S-1 is a new oral fluoropyrimidine derivative in which tegafur is combined with two 5-chloro-2, 4-dihydroxypyridine modulators and oteracil potassium, a potentiator of 5-fluorouracil's (5-FU's) antitumor activity that also decreases gastrointestinal toxicity. Combination chemotherapy with Gem and S-1 is reportedly well tolerated and benefits patients with advanced PDAC. Based on the results of the GEST study, S-1 is found to be non-inferior to Gem in patients' survival.
Therefore, in this study, the investigators replaced 5-FU and leucovorin in the FOLFIRINOX regimen with oral S-1, forming a SIRIOX regimen to treat patients with advanced pancreatic cancer, as first- or second-line chemotherapy.
- Conditions
- Carcinoma, Pancreatic Ductal
- Being tested
- S1, Oxaliplatin, Irinotecan
- Medical subject headings
- Carcinoma, Pancreatic Ductal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S1Drug
Patients are planned to receive the SIRIOX regimen including S-1 (BSA < 1.2m2, 40 mg/day; BSA = 1.2~1.4 m2, 60 mg/day; BSA = 1.4~1.6 m2, 80 mg/day; BSA > 1.6 m2, 100 mg/day; oral twice daily on days 1-7, days 15-21）of every cycle.
- 28 days a cycle.
OxaliplatinDrug
Patients are planned to receive the SIRIOX regimen including Oxaliplatin (OXA, 85 mg/m2; d1,d15) of every cycle.
- 28 days a cycle
IrinotecanDrug
Patients are planned to receive the SIRIOX regimen including Irinotecan (IRI, 180mg/m2; day 1,day 15) of every cycle.
- 28 days a cycle
| Study group | Role | What they receive |
|---|---|---|
| SIRIOX regimen | Experimental | 5-FU and leucovorin in the FOLFIRINOX regimen were replaced with oral S-1, forming the SIRIOX regimen(S1 plus irinotecan and oxaliplatin) Receives: Drug: S1; Drug: Oxaliplatin; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression free survival (PFS)
The time from the beginning of randomization to the earliest date of confirmation of tumor progression or the patient death for any reason. If the above criteria are not reached, the date of the last evaluation will be used.
Measured: 6 weeks (1.5 cycle)
Secondary outcomes (3)
objective response rate (ORR)
The proportion of patients whose tumors shrink to a certain amount for a certain period of time and include cases of complete response (CR) and partial response (PR). Calculated as: (CR cases + PR cases) / FAS × 100 (%); FAS (full analysis set) refers to the case of qualified patients, administered more than one case.
Tumor remission rates are calculated according to the RECIST guidelines (version 1.1)
Measured: 6 weeks (1.5 cycle)
overall survival (OS)
The time from the beginning of randomization to the earliest date of confirmation of the patient death for any reason.
Measured: through study completion, an average of 18 months
Toxicity evaluated according to the Common Terminology Criteria Adverse Events
Toxicity is evaluated according to the Common Terminology Criteria Adverse Events Version3.0,CTCAEv3.0
Measured: every week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2018
- Study start1 Jul 2020
- Primary completion31 Dec 2023 (estimated)
- Study completion1 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Pancreatic DuctalStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xian-Jun Yu, Fudan University
- Investigators
- Xianjun Yu, M.D., Ph.D., Study chair, 270 Dong An Road, Shanghai 200032, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03403101
- Sponsor's protocol ID
- CSPAC-020
- Status last verified
- Apr 2021
- First submitted
- 28 Nov 2017
- Last updated
- 9 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Single Arm, Open Label Study to Evaluate the Efficacy and Safety of the Combination of S-1, Irinotecan and Oxaliplatin (SIRIOX) in Treating Patients With Advanced Inoperable or Metastatic Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT03403101
- Acronym / sponsor ID
- CSPAC-020
- Conditions
- Carcinoma, Pancreatic Ductal
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 65 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 1 Jul 2024 (estimated)
- First posted
- 18 Jan 2018 (actual)
- 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.
Pancreatic cancer represents the most lethal of the common malignancies with a 5-year survival rate of less than 5%. For patients who are eligible for potentially curative resection, despite mortality and morbidity rates after surgery have improved, the recurrence rate is up to 85% within 2 years. FOLFIRINOX (fluoropyrimidine/leucovorin plus irinotecan and oxaliplatin) has been proved to significantly improve the prognosis and is recommended as first line treatment in patients with advanced pancreatic cancer. However, the regimen is limited due to the severe adverse effects. Thus, the investigators replaced 5-FU and leucovorin in the FOLFIRINOX regimen with oral S-1, a new oral fluoropyrimidine derivative which was proved to be the well-tolerated and effectively in large III phase randomized clinical trial, to form the SIRIOX regimen. A phase I clinical trial from Japan found that SOXIRI (S-1, oxaliplatin and irinotecan) works in patients with advanced pancreatic cancer. In this study, the researchers intend to investigate the activity and safety of the combination of this regimen in patients with advanced pancreatic cancer, as first- or second-line chemotherapy.
Detailed description
Pancreatic cancer (mainly pancreatic ductal adenocarcinoma, PDAC) is a disease with extremely poor prognosis, and is often fatal. Surgical resection is the only potentially curative technique for management of PDAC, but only approximately 15% to 20% of patients are candidates for pancreatectomy at the time of diagnosis Gemcitabine (Gem) is widely used as a standard chemotherapeutic agent for advanced pancreatic cancer. FOLFIRINOX (fluoropyrimidine/leucovorin plus irinotecan and oxaliplatin), compared with Gem, has been proved to significantly improve the objective response rate (31.6% VS. 9.4%, P < 0.001) and prolong the median survival time (11.1 months VS. 6.8 months, P < 0.001) for patients with metastatic pancreatic ductal adenocarcinoma(PDAC), who had a performance status of ECOG 0-1 score. However, it is undeniable that the adverse effects of FOLFIRINOX are severe. For example, the incidence of 3/4 grade neutrophil decrease in patients receiving FOLFIRINOX is significantly higher than those with Gem (45.7% VS. 21%, P < 0.001). Thus, it is difficult for many patients to receive standard FOLFIRINOX and benefit from the protocol. Therefore, the investigators aim to explore an improvement program of FOLFIRINOX, hoping to better benefit patients.
S-1 is a new oral fluoropyrimidine derivative in which tegafur is combined with two 5-chloro-2, 4-dihydroxypyridine modulators and oteracil potassium, a potentiator of 5-fluorouracil's (5-FU's) antitumor activity that also decreases gastrointestinal toxicity. Combination chemotherapy with Gem and S-1 is reportedly well tolerated and benefits patients with advanced PDAC. Based on the results of the GEST study, S-1 is found to be non-inferior to Gem in patients' survival.
Therefore, in this study, the investigators replaced 5-FU and leucovorin in the FOLFIRINOX regimen with oral S-1, forming a SIRIOX regimen to treat patients with advanced pancreatic cancer, as first- or second-line chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SIRIOX regimen | Experimental | Drug: S1, Drug: Oxaliplatin, Drug: Irinotecan5-FU and leucovorin in the FOLFIRINOX regimen were replaced with oral S-1, forming the SIRIOX regimen(S1 plus irinotecan and oxaliplatin) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients aged 18 - 75 years old at the time of signing the ICF.
- Patients with pathologically proved adenocarcinoma of pancreatic cancer and diagnosed with inoperable/metastatic disease (previous systemic chemotherapy, neoadjuvant or adjuvant are acceptable without Irinotecan, Oxaliplatin, or S1).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Adequate hematologic function defined as: absolute neutrophil count (ANC) >= 2,000/μL; platelets count >= 100,000/μL; hemoglobin must be >= 10 g/dL (can be corrected by growth factor or transfusion).
- Adequate hepatic function defined as: serum bilirubin =< 1.5-fold upper limit of normal (ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) =< 3-fold ULN (5-fold ULN if liver metastasis is observed).
Key exclusion criteria (13 listed)
- Patients who are unwilling or unable to comply with the study protocol;
- Existing anticancer treatment-related toxicities of Grades >= 2 (except for alopecia and neuropathy) according to Common Terminology Criteria for Adverse Events (CTCAE v4.03).
- Simultaneously using targeted therapies, such as Erlotinib, Nimotuzumab etc;
- Any severe or uncontrolled systemic disease (e.g., unstable or decompensated breathing, heart, liver or kidney disease, HIV infection, hypertension, severe arrhythmia, diabetes mellitus, massive active bleeding);
- Large operations were performed within 14 days before entering the study, or there were surgical incisions that were not completely healed;
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 |
|---|---|---|
| S1Patients are planned to receive the SIRIOX regimen including S-1 (BSA < 1.2m2, 40 mg/day; BSA = 1.2~1.4 m2, 60 mg/day; BSA = 1.4~1.6 m2, 80 mg/day; BSA > 1.6 m2, 100 mg/day; oral twice daily on days 1-7, days 15-21）of every cycle. • 28 days a cycle. | Drug | SIRIOX regimen |
| OxaliplatinPatients are planned to receive the SIRIOX regimen including Oxaliplatin (OXA, 85 mg/m2; d1,d15) of every cycle. • 28 days a cycle | Drug | SIRIOX regimen |
| IrinotecanPatients are planned to receive the SIRIOX regimen including Irinotecan (IRI, 180mg/m2; day 1,day 15) of every cycle. • 28 days a cycle | Drug | SIRIOX regimen |
Primary outcome
progression free survival (PFS)
Time frame: 6 weeks (1.5 cycle)
The time from the beginning of randomization to the earliest date of confirmation of tumor progression or the patient death for any reason. If the above criteria are not reached, the date of the last evaluation will be used.
3 secondary outcomes
objective response rate (ORR)
Time frame: 6 weeks (1.5 cycle)
overall survival (OS)
Time frame: through study completion, an average of 18 months
Toxicity evaluated according to the Common Terminology Criteria Adverse Events
Time frame: every week
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2021.
- Individual participant dataSharing planned: Undecided
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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.
Xianjun Yu, M.D., Ph.D. study chair
270 Dong An Road, Shanghai 200032, China
2 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 S1, Oxaliplatin and Irinotecan in people with Carcinoma, Pancreatic Ductal, run by Fudan University at 2 sites in China.
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 11 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 9 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xianjun Yu, M.D., Ph.D. (+86 21 64175590, yuxianjun88@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
progression free survival (PFS) (time frame: 6 weeks (1.5 cycle)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Apr 2021.