Metastatic Pancreatic AdenocarcinomaPhase 2NCT07076212
Evaluating NALIRIFOX vs Modified Gemcitabine, Nab-Paclitaxel and Cisplatin in Patients With Locally Advanced and Metastatic Pancreatic Adenocarcinoma
A Phase 2 study testing Liposomal Irinotecan, Oxaliplatin and 5-Fluorouracil in people with Metastatic Pancreatic Adenocarcinoma and Locally Advanced Pancreatic Adenocarcinoma, run by Medical University of South Carolina at 2 sites in United States.
Trial summary
This is a single-center, open-label, randomized Phase 2 trial to evaluate the efficacy of NALIRIFOX (Arm 1) vs mGAP (Arm 2) in previously untreated patients with locally advanced (unresectable) and metastatic pancreatic ductal adenocarcinoma (PDAC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Pancreatic Adenocarcinoma, Locally Advanced Pancreatic Adenocarcinoma
- What is being tested?
- Liposomal Irinotecan, Oxaliplatin and 5-Fluorouracil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 2 sitesUnited States
- Study dates
- 2 Apr 2026to Nov 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged ≥18 years
- For females of reproductive potential: use of highly effective contraception for at least 1 month before screening and agreement to use such a method during study participation and for an additional 9 months after the end of the last dose of study medication administration
- Female patients including WOCBP must test negative for pregnancy at the time of screening based on a urine or serum pregnancy test.
- For males of reproductive potential: use of condoms or other methods to ensure effective contraception with a partner during the study and for 4 months after the last dose of study medication.
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- Histologically or cytologically confirmed locally advanced or metastatic PDAC that has not been previously treated
- Radiographically confirmed measurable (per RECIST 1.1) locally advanced or metastatic PDAC per the National Comprehensive Cancer Network (NCCN) definition.
- Inoperable status due to the presence of locally advanced, unresectable disease with or metastases.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Hematological, biochemical, and organ function inclusion criteria:
- Absolute neutrophil count (ANC) ≥1500/mm3 without the use of hemopoietic growth factors within 7 days before treatment
- Platelet count ≥100,000/mm3.
- International normalized ratio (INR) <1.5 unless the patient is receiving anticoagulation therapy, in which case a therapeutic INR is acceptable. Anticoagulation therapy with low-molecular weight heparin or warfarin, whether medically indicated, is permitted.
- Adequate renal function, as evidenced by serum/plasma creatinine level <1.6 mg/dL
Who cannot join
- Pregnancy or lactation
- Treatment with another investigational drug or other intervention within 30 days of protocol initiation.
- Known hypersensitivity/allergic reaction to any of the components of the therapeutic agents in mGAP or NALIRIFOX.
- Any other medical or social condition deemed by the investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, and participate in the study or who is likely to interfere with the interpretation of the results.
- Unwilling or unable to comply with study procedures and/or study visits.
- Uncontrolled, active infection
- Histologic diagnosis other than adenocarcinoma.
- Medical co-morbidities, that preclude major abdominal surgery
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, 29425
HCC Clinical Trials Office, 843-792-9321, hcc-clinical-trials@musc.edu
Albert Lockhart, MD
- Recruiting
Medical University of South Carolina Hollings Cancer Center
Charleston, South Carolina, 29425
HCC Clinical Trials Office, 843-792-9321, hcc-clinical-trials@musc.edu
About this study
Official title: Phase II Study Evaluating NALIRIFOX Versus Modified Gemcitabine, Nab-Paclitaxel and Cisplatin in Patients With Locally Advanced and Metastatic Pancreatic Adenocarcinoma
This is a single-center, open-label, randomized Phase 2 trial to evaluate the efficacy of NALIRIFOX (Arm 1) vs mGAP (Arm 2) in previously untreated patients with locally advanced (unresectable) and metastatic pancreatic ductal adenocarcinoma (PDAC).
Read the detailed description
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies in the United States and is a leading cause of cancer-related deaths. In the metastatic setting, treatment consists of systemic chemotherapy in hopes of palliating symptoms and prolonging survival. However, prognosis remains very poor, and patients will invariably succumb to disease-related complications. Therefore, there is a critical need to identify new first-line systemic therapeutic options in hopes of improving clinical outcomes in PDAC.
FOLFIRINOX (leucovorin, 5-flurouracil, irinotecan, oxaliplatin) became a standard of care systemic therapy option in metastatic PDAC, largely based on the findings from the Phase III ACCORD 11 study, where the objective response rate (ORR) was significantly higher with FOLFIRINOX vs single-agent gemcitabine (32% vs 9%). Median progression-free survival (PFS) (6.4 months vs 3.3 months) and overall survival (OS) (11.1 months vs 6.8 months) were higher as well. However, a recent Phase I/II study demonstrated tolerability of the chemotherapy combination liposomal irinotecan, oxaliplatin, 5-fluorouracil, and leucovorin (NALIRIFOX) in locally advanced and metastatic PDAC. This has been followed by a randomized Phase III study evaluating first-line NALIRIFOX vs gemcitabine plus nab-paclitaxel, which has demonstrated greater ORR with NALIRIFOX than gemcitabine plus nab-paclitaxel (41.8% vs 36.2%). Both median PFS (7.4 months vs 5.6 months) and OS (11.1 months vs 9.2 months) were significantly higher with NALIRIFOX than with gemcitabine plus nab-paclitaxel as well. In light of these findings, NALIRIFOX use in treatment-naïve patients is increasing.
As suggested above, gemcitabine combinations have elicited treatment responses in advanced PDAC as well. Efficacy of first-line gemcitabine plus nab-paclitaxel was demonstrated in the MPACT trial, where a higher ORR and median OS was noted in the combination arm vs single-agent gemcitabine (23% vs 7% and 8.7 months vs 6.7 months, respectively). This led to its indication for use in metastatic and locally advanced PDAC. Additionally, gemcitabine plus cisplatin was noted to have an ORR of 74% in germline BRCA1/2 and PALB2 mutated advanced PDAC. A recent small Phase II study demonstrated the use of the triplet regimen, gemcitabine plus nab-paclitaxel plus cisplatin administered on Day 1 and Day 8 of a 21-day cycle as having clinical activity in metastatic PDAC where ORR was 71% with median PFS and median OS of 10.1 months and 16.4 months, respectively. However, it remains unknown whether this triplet regimen is more efficacious than NALIRIFOX.
Therefore, investigators propose evaluating whether gemcitabine plus nab-paclitaxel plus cisplatin (mGAP) will lead to greater ORR than NALIRIFOX in previously untreated patients with locally advanced and metastatic PDAC. Of note, despite the high ORR observed with this regimen, 2 of 3 deaths in the study were attributed by the authors to the chemotherapy combination. Due to this toxicity, rather than administering the triplet regimen on Day 1 and Day 8 of a 21-day cycle as done in the Phase Ib/II study, investigators will proceed with Day 1 and Day 15 administration of a 28-day cycle. Investigators hypothesize that gemcitabine plus nab-paclitaxel plus cisplatin will have a greater ORR than NALIRIFOX and lead to improved secondary outcome measurements of BOR, DOR, DCR, PFS, OS, and toxicity profile. Investigators will determine its clinical utility relative to NALIRIFOX in the first-line setting based on standard radiology used to measure treatment response. Findings from this study may have implications for changing the standard of care systemic therapeutic approach in patients with treatment-naïve locally advanced and metastatic PDAC.
- Being tested
- Liposomal Irinotecan, Oxaliplatin, 5-Fluorouracil, Leucovorin, Gemcitabine (mg/m²)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liposomal IrinotecanDrug
50 mg/m2 will be administered on Day 1 of a 2-week cycle
OxaliplatinDrug
60 mg/m2 will be administered on Day 1 of a 2-week cycle
5-FluorouracilDrug
5-fluorouracil (2400 mg/m2 over 46 hours) will begin administration on Day 1 of a 2-week cycle
LeucovorinDrug
400 mg/m2 will be administered on Day 1 of a 2-week cycle
Gemcitabine (mg/m²)Drug
1000 mg/m2 will be administered on Day 1 and Day 15 of a 4-week cycle
Nab-paclitaxelDrug
125 mg/m2 will be administered on Day 1 and Day 15 of a 4-week cycle
CisplatinDrug
25 mg/m2 will be administered on Day 1 and Day 15 of a 4-week cycle
| Study group | Role | What they receive |
|---|---|---|
| NALIRIFOX | Experimental | Not described Receives: Drug: Liposomal Irinotecan; Drug: Oxaliplatin; Drug: 5-Fluorouracil; Drug: Leucovorin |
| mGAP | Experimental | Not described Receives: Drug: Gemcitabine (mg/m²); Drug: Nab-paclitaxel; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR) assessed by imaging.
Overall response rate (ORR) defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by imaging completed every 8 weeks.
Measured: Up to 30 months
Secondary outcomes (6)
Best overall response (BOR) assessed by imaging.
Best overall response (BOR) defined as a patient's best response across all response evaluations by RECIST v1.1 (CR, PR, stable disease [SD], or progressive disease [PD]) as assessed by imaging completed every 8 weeks.
Measured: Up to 30 months
Duration of response (DOR).
Duration of response (DOR) defined as the time interval between first evaluation of CR or PR and the first occurrence of progression or death due to any cause.
Measured: Up to 30 months
Disease control rate (DCR).
Disease control rate (DCR) defined as the proportion of patients with a best overall response of CR, PR or SD.
Measured: Up to 30 months
Progression-free survival (PFS).
Progression-free survival (PFS) defined as the time from randomization to progression or death due to any cause.
Measured: Up to 30 months
Overall survival (OS).
Overall survival (OS) defined as the time from randomization to death from any cause.
Measured: Up to 30 months
Toxicity profile of each chemotherapy regimen.
Toxicity profile of each chemotherapy regimen as determined by AEs, SAEs and TEAEs and based on CTCAE v5.0
Measured: Up to 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2025
- Study start2 Apr 2026
- Primary completionMay 2028 (estimated)
- Study completionNov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Pancreatic AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Medical University of South CarolinaThe 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
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Albert Lockhart, MD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07076212
- Sponsor's protocol ID
- 103973
- Status last verified
- May 2026
- First submitted
- 14 Jul 2025
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study Evaluating NALIRIFOX Versus Modified Gemcitabine, Nab-Paclitaxel and Cisplatin in Patients With Locally Advanced and Metastatic Pancreatic Adenocarcinoma
- ClinicalTrials.gov ID
- NCT07076212
- Acronym / sponsor ID
- 103973
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Study start
- 2 Apr 2026 (actual)
- Primary completion
- May 2028 (estimated)
- Study completion
- Nov 2029 (estimated)
- First posted
- 22 Jul 2025 (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.
This is a single-center, open-label, randomized Phase 2 trial to evaluate the efficacy of NALIRIFOX (Arm 1) vs mGAP (Arm 2) in previously untreated patients with locally advanced (unresectable) and metastatic pancreatic ductal adenocarcinoma (PDAC).
Detailed description
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies in the United States and is a leading cause of cancer-related deaths. In the metastatic setting, treatment consists of systemic chemotherapy in hopes of palliating symptoms and prolonging survival. However, prognosis remains very poor, and patients will invariably succumb to disease-related complications. Therefore, there is a critical need to identify new first-line systemic therapeutic options in hopes of improving clinical outcomes in PDAC.
FOLFIRINOX (leucovorin, 5-flurouracil, irinotecan, oxaliplatin) became a standard of care systemic therapy option in metastatic PDAC, largely based on the findings from the Phase III ACCORD 11 study, where the objective response rate (ORR) was significantly higher with FOLFIRINOX vs single-agent gemcitabine (32% vs 9%). Median progression-free survival (PFS) (6.4 months vs 3.3 months) and overall survival (OS) (11.1 months vs 6.8 months) were higher as well. However, a recent Phase I/II study demonstrated tolerability of the chemotherapy combination liposomal irinotecan, oxaliplatin, 5-fluorouracil, and leucovorin (NALIRIFOX) in locally advanced and metastatic PDAC. This has been followed by a randomized Phase III study evaluating first-line NALIRIFOX vs gemcitabine plus nab-paclitaxel, which has demonstrated greater ORR with NALIRIFOX than gemcitabine plus nab-paclitaxel (41.8% vs 36.2%). Both median PFS (7.4 months vs 5.6 months) and OS (11.1 months vs 9.2 months) were significantly higher with NALIRIFOX than with gemcitabine plus nab-paclitaxel as well. In light of these findings, NALIRIFOX use in treatment-naïve patients is increasing.
As suggested above, gemcitabine combinations have elicited treatment responses in advanced PDAC as well. Efficacy of first-line gemcitabine plus nab-paclitaxel was demonstrated in the MPACT trial, where a higher ORR and median OS was noted in the combination arm vs single-agent gemcitabine (23% vs 7% and 8.7 months vs 6.7 months, respectively). This led to its indication for use in metastatic and locally advanced PDAC. Additionally, gemcitabine plus cisplatin was noted to have an ORR of 74% in germline BRCA1/2 and PALB2 mutated advanced PDAC. A recent small Phase II study demonstrated the use of the triplet regimen, gemcitabine plus nab-paclitaxel plus cisplatin administered on Day 1 and Day 8 of a 21-day cycle as having clinical activity in metastatic PDAC where ORR was 71% with median PFS and median OS of 10.1 months and 16.4 months, respectively. However, it remains unknown whether this triplet regimen is more efficacious than NALIRIFOX.
Therefore, investigators propose evaluating whether gemcitabine plus nab-paclitaxel plus cisplatin (mGAP) will lead to greater ORR than NALIRIFOX in previously untreated patients with locally advanced and metastatic PDAC. Of note, despite the high ORR observed with this regimen, 2 of 3 deaths in the study were attributed by the authors to the chemotherapy combination. Due to this toxicity, rather than administering the triplet regimen on Day 1 and Day 8 of a 21-day cycle as done in the Phase Ib/II study, investigators will proceed with Day 1 and Day 15 administration of a 28-day cycle. Investigators hypothesize that gemcitabine plus nab-paclitaxel plus cisplatin will have a greater ORR than NALIRIFOX and lead to improved secondary outcome measurements of BOR, DOR, DCR, PFS, OS, and toxicity profile. Investigators will determine its clinical utility relative to NALIRIFOX in the first-line setting based on standard radiology used to measure treatment response. Findings from this study may have implications for changing the standard of care systemic therapeutic approach in patients with treatment-naïve locally advanced and metastatic PDAC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NALIRIFOX | Experimental | Drug: Liposomal Irinotecan, Drug: Oxaliplatin, Drug: 5-Fluorouracil, Drug: Leucovorin |
| mGAP | Experimental | Drug: Gemcitabine (mg/m²), Drug: Nab-paclitaxel, Drug: Cisplatin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged ≥18 years
- For females of reproductive potential: use of highly effective contraception for at least 1 month before screening and agreement to use such a method during study participation and for an additional 9 months after the end of the last dose of study medication administration
- Female patients including WOCBP must test negative for pregnancy at the time of screening based on a urine or serum pregnancy test.
Key exclusion criteria (8 listed)
- Pregnancy or lactation
- Treatment with another investigational drug or other intervention within 30 days of protocol initiation.
- Known hypersensitivity/allergic reaction to any of the components of the therapeutic agents in mGAP or NALIRIFOX.
- Any other medical or social condition deemed by the investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, and participate in the study or who is likely to interfere with the interpretation of the results.
- Unwilling or unable to comply with study procedures and/or study visits.
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 |
|---|---|---|
| Liposomal Irinotecan50 mg/m2 will be administered on Day 1 of a 2-week cycle | Drug | NALIRIFOX |
| Oxaliplatin60 mg/m2 will be administered on Day 1 of a 2-week cycle | Drug | NALIRIFOX |
| 5-Fluorouracil5-fluorouracil (2400 mg/m2 over 46 hours) will begin administration on Day 1 of a 2-week cycle | Drug | NALIRIFOX |
| Leucovorin400 mg/m2 will be administered on Day 1 of a 2-week cycle | Drug | NALIRIFOX |
| Gemcitabine (mg/m²)1000 mg/m2 will be administered on Day 1 and Day 15 of a 4-week cycle | Drug | mGAP |
| Nab-paclitaxel125 mg/m2 will be administered on Day 1 and Day 15 of a 4-week cycle | Drug | mGAP |
| Cisplatin25 mg/m2 will be administered on Day 1 and Day 15 of a 4-week cycle | Drug | mGAP |
Primary outcome
Overall response rate (ORR) assessed by imaging.
Time frame: Up to 30 months
Overall response rate (ORR) defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by imaging completed every 8 weeks.
6 secondary outcomes
Best overall response (BOR) assessed by imaging.
Time frame: Up to 30 months
Duration of response (DOR).
Time frame: Up to 30 months
Disease control rate (DCR).
Time frame: Up to 30 months
Progression-free survival (PFS).
Time frame: Up to 30 months
Overall survival (OS).
Time frame: Up to 30 months
Toxicity profile of each chemotherapy regimen.
Time frame: Up to 30 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Individual participant dataSharing planned: No
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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.
Albert Lockhart, MD principal investigator
Medical University of South Carolina
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 Liposomal Irinotecan, Oxaliplatin and 5-Fluorouracil in people with Metastatic Pancreatic Adenocarcinoma and Locally Advanced Pancreatic Adenocarcinoma, run by Medical University of South Carolina at 2 sites in United States.
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 15 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 6 May 2026. 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 United States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact HCC Clinical Trials Office, MD (843-792-9321, hcc-clinical-trials@musc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (ORR) assessed by imaging. (time frame: Up to 30 months). 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 6 May 2026; AzTrials last refreshed its copy on 7 Nov 2026.