NCT02551991

Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma

Completed Phase 2 Results posted Last updated 10 October 2022

What this trial tests

Phase 2 trial testing nal-IRI in Pancreatic Cancer in 56 participants. Completed in 15 February 2021.

Timeline

19 October 2015

Primary endpoint
15 February 2021

15 February 2021

Quick facts

Lead sponsor	Ipsen
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	56
Start date	19 October 2015
Primary completion	15 February 2021
Estimated completion	15 February 2021
Sites	36 locations across United States, Australia, Spain

Drugs / interventions tested

• nal-IRI
• 5 fluorouracil — full drug profile →
• Leucovorin (leucovorin) — full drug profile →
• Oxaliplatin (Oxaliplatin) — full drug profile →

Conditions studied

• Pancreatic Cancer — all drugs for Pancreatic Cancer →

Sponsor

Ipsen — full company profile →

Who can join

18 and older, any sex, with Pancreatic Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT) Primary · From the start of the first study treatment (Cycle 1 Day 1) up to 14 days after the second dose of study treatment, maximum of 42 days

Adverse events (AEs) were considered to be DLTs if they occurred during the safety evaluation period (i.e, 28 days of Cycle 1; or 14 days after the second dose of study treatment if there was a treatment delay) and were deemed related to the study treatment regimen. Any AE that was related to disease progression was not considered a DLT.

Group	Value	95% CI
Dose Exploration: Cohort 1	2
Dose Exploration: Cohort -1	1
Dose Exploration: Cohort -2B	2
Dose Exploration: Cohort -3	0

Median Progression Free Survival (PFS) Secondary · RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, end of treatment (EoT) visit, then every 2 months thereafter (maximum of 278 weeks).

The PFS was defined as the time from date of first study treatment to the first documented radiographical progression of disease (PD), per investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, or death from any cause, whichever comes first. The PFS was calculated using Kaplan-Meier technique.

Group	Value	95% CI
Dose Exploration: Cohort 1	9.7	2.96 – NA
Dose Exploration: Cohort -1	32.3	0.53 – NA
Dose Exploration: Cohort -2B	9.2	0.46 – NA
Dose Exploration: Cohort -3	3.8	1.22 – 5.78
Dose Expansion: Cohort -1	9.2	7.59 – 11.20
Cohort -1: Pooled	9.2	7.59 – 11.96

Best Overall Response (BOR) Secondary · RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).

The BOR was defined as the best response (complete response \[CR\] + partial response \[PR\] + stable disease \[SD\]) recorded from the start of study treatment until disease progression or start of new anticancer therapy using RECIST Version 1.1.

Group	Value	95% CI
Dose Exploration: Cohort 1	2
Dose Exploration: Cohort -1	6
Dose Exploration: Cohort -2B	4
Dose Exploration: Cohort -3	4
Dose Expansion: Cohort -1	20
Cohort -1: Pooled	26

Overall Response Rate (ORR) Secondary · RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).

The ORR was defined as the percentage of participants with a BOR characterized as either a CR or PR relative to the total number of evaluable participants using RECIST Version 1.1. Evaluable participants were defined as treated participants with measurable disease at baseline.

Group	Value	95% CI
Dose Exploration: Cohort 1	0	0 – 41.0
Dose Exploration: Cohort -1	42.9	9.9 – 81.6
Dose Exploration: Cohort -2B	30.0	6.7 – 65.2
Dose Exploration: Cohort -3	14.3	0.4 – 57.9
Dose Expansion: Cohort -1	32.0	14.9 – 53.5
Cohort -1: Pooled	34.4	18.6 – 53.2

Disease Control Rate (DCR) Secondary · At Week 16

The DCR was defined as percentage of participants with CR or PR or SD or Non-PD/Non-CR, per RECIST Version 1.1 relative to total number of treated participants with measurable disease at baseline.

Group	Value	95% CI
Dose Exploration: Cohort 1	42.9	9.9 – 81.6
Dose Exploration: Cohort -1	71.4	29.0 – 96.3
Dose Exploration: Cohort -2B	40.0	12.2 – 73.8
Dose Exploration: Cohort -3	28.6	3.7 – 71.0
Dose Expansion: Cohort -1	72.0	50.6 – 87.9
Cohort -1: Pooled	71.9	53.3 – 86.3

Median Overall Survival (OS) Secondary · RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).

The OS was the time from date of first study treatment to the date of death from any cause. Participant survival data were collected from all available sources. The OS was calculated using Kaplan-Meier technique.

Group	Value	95% CI
Dose Exploration: Cohort 1	12.6	3.98 – 21.03
Dose Exploration: Cohort -1	12.5	0.53 – 12.71
Dose Exploration: Cohort -2B	16.6	0.69 – 26.74
Dose Exploration: Cohort -3	5.8	1.35 – 14.65
Dose Expansion: Cohort -1	12.7	8.18 – 23.66
Cohort -1: Pooled	12.6	8.74 – 19.12

Median Duration of Response (DoR) Secondary · RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).

The DoR was defined as the time from the first date of response (CR or PR) to first date of documented radiographical PD, per investigator using RECIST Version 1.1. This only applied to participants with CR or PR. If a participant was given a new anticancer therapy prior to first response, DoR was not calculated. The DoR was calculated using Kaplan-Meier technique.

Group	Value	95% CI
Dose Exploration: Cohort -1	28.4	3.52 – NA
Dose Exploration: Cohort -2B	NA	NA – 16.39
Dose Expansion: Cohort -1	9.4	2.20 – NA
Cohort -1: Pooled	9.4	3.52 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to 30 days after the date of last study treatment administration or until the start of alternative anticancer therapy, approximately 1008 days. All-Cause Mortality are reported from first participant enrolled to last participant died, approximately 1946 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dose Exploration: Cohort 1

Serious: 6/7 (86%)

Deaths: 5/7

Dose Exploration: Cohort -1

Serious: 2/7 (29%)

Deaths: 7/7

Dose Exploration: Cohort -2B

Serious: 7/10 (70%)

Deaths: 8/10

Dose Exploration: Cohort -3

Serious: 4/7 (57%)

Deaths: 7/7

Dose Expansion: Cohort -1

Serious: 15/25 (60%)

Deaths: 17/25

Serious adverse events (45 terms)

Reaction	System	Dose Exploration: Cohort 1	Dose Exploration: Cohort -1	Dose Exploration: Cohort -2B	Dose Exploration: Cohort -3	Dose Expansion: Cohort -1
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Abdominal Pain	Gastrointestinal disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Colitis	Gastrointestinal disorders	—	—	—	—	—
Febrile Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Enterocolitis	Gastrointestinal disorders	—	—	—	—	—
Small Intestinal Obstruction	Gastrointestinal disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Duodenal Ulcer	Gastrointestinal disorders	—	—	—	—	—
Enteritis	Gastrointestinal disorders	—	—	—	—	—
Intestinal Obstruction	Gastrointestinal disorders	—	—	—	—	—
Large Intestinal Obstruction	Gastrointestinal disorders	—	—	—	—	—
Malignant Gastrointestinal Obstruction	Gastrointestinal disorders	—	—	—	—	—
Oesophageal Varices Haemorrhage	Gastrointestinal disorders	—	—	—	—	—
Pancreatitis	Gastrointestinal disorders	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—
Upper Gastrointestinal Haemorrhage	Gastrointestinal disorders	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Anaemia of Malignant Disease	Blood and lymphatic system disorders	—	—	—	—	—
Bacterial Sepsis	Infections and infestations	—	—	—	—	—
Clostridium Difficile Colitis	Infections and infestations	—	—	—	—	—
Neutropenic Sepsis	Infections and infestations	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—

Other adverse events (232 terms — click to expand)

Reaction	System	Dose Exploration: Cohort 1	Dose Exploration: Cohort -1	Dose Exploration: Cohort -2B	Dose Exploration: Cohort -3	Dose Expansion: Cohort -1
Nausea	Gastrointestinal disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—
Neuropathy peripheral	Nervous system disorders	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—	—
Depression	Psychiatric disorders	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—	—	—	—
Dysgeusia	Nervous system disorders	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
White blood cell count decreased	Investigations	—	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—	—	—
Blood bilirubin increased	Investigations	—	—	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—	—	—
Pancreatic failure	Gastrointestinal disorders	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—
Mucosal inflammation	General disorders	—	—	—	—	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—	—	—	—	—

Most-reported serious reactions: Vomiting, Abdominal Pain, Nausea, Diarrhoea, Colitis, Febrile Neutropenia, Enterocolitis, Small Intestinal Obstruction.

Data from ClinicalTrials.gov NCT02551991 adverse events section.

Sponsor's own description

This is an open-label, phase 2 non-comparative study to assess the safety, tolerability, and preliminary efficacy of nal-IRI in combination with other anticancer therapies in patients not previously treated for metastatic pancreatic adenocarcinoma. This study will assess the following regimen:

• nal-IRI + 5-fluorouracil (5-FU)/leucovorin (LV) + oxaliplatin

The study will be conducted in two parts:

Part 1, consisting of an initial dose exploration (Part 1A) followed by dose expansion (Part 1B) of the irinotecan liposome injection +5-FU/LV + oxaliplatin regimen and Part 2, consisting of a comparison of irinotecan liposome injection-containing regimen versus nab-paclitaxel plus gemcitabine. The comparative Part 2 was removed in a protocol amendment, dated 11 April 2018 (Version 6.0), before it was initiated, as this comparative part of the study is being undertaken as a stand-alone phase III study D-US-60010-001. This CSR only pertains to the single-arm dose exploration and dose expansion Part 1 results and no further reference is made to the comparative Part 2.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial.
   Wainberg ZA, Melisi D, Macarulla T, Pazo Cid R, et al · · 2023 · cited 333× · PMID 37708904 · DOI 10.1016/s0140-6736(23)01366-1
2. New Treatment Strategies for Metastatic Pancreatic Ductal Adenocarcinoma.
   Singh RR, O'Reilly EM. · · 2020 · cited 119× · PMID 32306207 · DOI 10.1007/s40265-020-01304-0
3. Onivyde for the therapy of multiple solid tumors.
   Zhang H. · · 2016 · cited 114× · PMID 27284250 · DOI 10.2147/ott.s105587
4. Improved Efficacy and Reduced Toxicity Using a Custom-Designed Irinotecan-Delivering Silicasome for Orthotopic Colon Cancer.
   Liu X, Jiang J, Chan R, Ji Y, et al · · 2019 · cited 88× · PMID 30525443 · DOI 10.1021/acsnano.8b06164
5. Pancreatic Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells.
   Pelosi E, Castelli G, Testa U. · · 2017 · cited 74× · PMID 29156578 · DOI 10.3390/biomedicines5040065
6. Nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience.
   Glassman DC, Palmaira RL, Covington CM, Desai AM, et al · · 2018 · cited 72× · PMID 29945562 · DOI 10.1186/s12885-018-4605-1
7. Nano albumin bound-paclitaxel in pancreatic cancer: Current evidences and future directions.
   Giordano G, Pancione M, Olivieri N, Parcesepe P, et al · · 2017 · cited 67× · PMID 28932079 · DOI 10.3748/wjg.v23.i32.5875
8. A real-world analysis of second-line treatment options in pancreatic cancer: liposomal-irinotecan plus 5-fluorouracil and folinic acid.
   Kieler M, Unseld M, Bianconi D, Scheithauer W, et al · · 2019 · cited 41× · PMID 31360237 · DOI 10.1177/1758835919853196