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First Line Metastatic Pancreatic Cancer : 5FU/LV+Nal-IRI, Gemcitabine+Nab-paclitaxel or a Sequential Regimen of 2 Months 5FU/LV+Nal-IRI (FUNGEMAX)

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ClinicalTrials.gov Identifier: NCT03693677
Recruitment Status : Recruiting
First Posted : October 3, 2018
Last Update Posted : July 19, 2019
Sponsor:
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive

Brief Summary:

In Europe, pancreatic cancer (PC) is the 7th most common cancer and the 5th leading cause of cancer death in Europe. Each year, the number of deaths due to prostate cancer is almost as high as the number of new cases diagnosed reflecting the poor prognosis associated with this disease. PC is insidious and is often diagnosed late. Despite advances in the management of other more common gastrointestinal cancers, the treatment of PC has had few benefits inherent in recent advances in digestive oncology. Gemcitabine has thus remained the reference treatment for more than 10 years.

Recent studies have shown that gemcitabine/Nab-paclitaxel combination therapy is more effective in PC than gemcitabine-based therapy alone. In addition, multidrug therapy approaches (Irinotecan-5FU/LV) have also emerged to avoid the emergence of resistance to treatments while limiting toxicities. The recently developed Nal-IRI has also shown interesting efficacy in patients with metastatic PC previously treated with gemcitabine, with improved overall survival median and limited toxicity. Based on this information, the NAPOLI trial was conducted in patients with second line PC comparing the efficacy of Nal-IRI/5FU/LV or Nal-IRI and 5FU/LV alone; in this key study, the combination Nal-IRI/5FU/LV treatment was more effective than monotherapies (Nal-IRI or 5FU/LV alone).

Based on all these data, a Phase II trial testing the standard of care gemcitabine/nab-paclitaxel vs Nal-IRI/5FU/LV vs Nal-IRI/5FU/LV 2-months sequential regimen followed by gemcitabine/nab-paclitaxel will be performed. This will allow us to i) know the tolerance and efficacy of Nal-IRI/5FU/LV in the first line of treatment, ii) test a new sequential strategy with Nal-IRI but also iii) compare our results in the experimental arms with one of the two world standard therapeutic regimens: gemcitabine + nab-Paclitaxel. All this in order to improve the management of patients with PC from the first line of treatment.


Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Cancer Drug: Irinotecan Liposomal Injection Drug: 5-FU/LV Drug: Nab-Paclitaxel Drug: Gemcitabine Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 288 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Study Comparing 5FU/LV+Nal-IRI, Gemcitabine+Nab-paclitaxel or a Sequential Regimen of 2 Months 5FU/LV+Nal-IRI Followed by Two Months of Gemcitabine+Nab-paclitaxel, in Metastatic Pancreatic Cancer
Actual Study Start Date : November 16, 2018
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2024


Arm Intervention/treatment
Experimental: Nal-IRI/5-FU/LV + Nab-paclitaxel/Gemcitabine alternatively

Nal-IRI plus 5-FU/LV and Nab-Paclitaxel plus Gemcitabine alternately every two months

  • Nal-IRI at 80 mg/m2 IV over 90 minutes followed by folinic acid (leucovorin 400 mg/m2 IV, or Elvorin 200 mg/m2 IV over 30 minutes) then by 5-FU 2400 mg/m2 IV over 46-hours, every 2 weeks.
  • Nab-Paclitaxel + Gemcitabine (6 injections, one injection three weeks out of four; so ≈ 2 months per cycle)

Day 1 (D1): Nab-Paclitaxel plus Gemcitabine at the dose of :

  • Gemcitabine: 1000 mg/m² in 500 ml normal saline infusion at a fixed dose rate of 10 mg/m²/min (i.e. 100 min).
  • Nab-Paclitaxel: 125 mg/m2 This treatment is administered at D1, D8, D15 and at D29, D36, D43.
Drug: Irinotecan Liposomal Injection
Nal-IRI at 80 mg/m2 IV over 90 minutes
Other Name: Nal-IRI

Drug: 5-FU/LV
5-FU 2400 mg/m2 IV over 46-hours, every 2 weeks.

Drug: Nab-Paclitaxel
Nab-Paclitaxel: 125 mg/m2 This treatment is administered at D1, D8, D15 and at D29, D36, D43.

Drug: Gemcitabine
1000 mg/m² in 500 ml normal saline infusion at a fixed dose rate of 10 mg/m²/min (i.e. 100 min). This treatment is administered at D1, D8, D15 and at D29, D36, D43.

Experimental: Nal-IRI/5-FU/LV
Nal-IRI plus 5-FU/LV Nal-IRI at 80 mg/m2 IV over 90 minutes followed by folinic acid (leucovorin 400 mg/m2 IV, or Elvorin 200 mg/m2 IV over 30 minutes) then by 5-FU 2400 mg/m2 IV over 46-hours, every 2 weeks.
Drug: Irinotecan Liposomal Injection
Nal-IRI at 80 mg/m2 IV over 90 minutes
Other Name: Nal-IRI

Drug: 5-FU/LV
5-FU 2400 mg/m2 IV over 46-hours, every 2 weeks.

Active Comparator: Nab-paclitaxel/Gemcitabine

Nab-Paclitaxel plus Gemcitabine Nab-Paclitaxel + Gemcitabine (6 courses, one course three weeks out of four; so ≈ 2 months per cycle)

Day 1 (D1): Nab-Paclitaxel + Gemcitabine at the dose of :

  • Gemcitabine: 1000 mg/m² in 500 ml normal saline infusion at a fixed dose rate of 10 mg/m²/min (i.e. 100 min).
  • Nab-Paclitaxel: 125 mg/m2 This treatment is administered at D1, D8, D15 and at D29, D36, D43.
Drug: Nab-Paclitaxel
Nab-Paclitaxel: 125 mg/m2 This treatment is administered at D1, D8, D15 and at D29, D36, D43.

Drug: Gemcitabine
1000 mg/m² in 500 ml normal saline infusion at a fixed dose rate of 10 mg/m²/min (i.e. 100 min). This treatment is administered at D1, D8, D15 and at D29, D36, D43.




Primary Outcome Measures :
  1. The progression free survival at 6 months according to the RECIST 1.1 criteria [ Time Frame: 6 months ]
    PFS is defined as the time between the date of randomization and the date of the first radiological and/or clinical progression or the date of death (for whatever reason). Patients living without progression will be censured at date of last news. Progression is assessed by investigator and central review according to RECIST v1.1 criteria.


Secondary Outcome Measures :
  1. Progression free survival at 6 months (according to central review) [ Time Frame: 6 months ]
    PFS is defined as the time between the date of randomization and the date of the first radiological and/or clinical progression or the date of death (for whatever reason). Patients living without progression will be censured at date of last news. Progression is assessed by investigator and central review according to RECIST v1.1 criteria.

  2. Best objective response rate [ Time Frame: An average of 1 year ]
    BOR is defined as complete or partial response rate according to scans and RECIST v1.1 criteria over the entire treatment period.

  3. Overall survival [ Time Frame: 2 years ]
    OS is defined as the time between the date of randomization and the date of death (whatever the cause). Alive patients will be censured at date of last news.

  4. Time to treatment failure [ Time Frame: An average of 1 year ]
    Time to treatment failure is defined as the time between the date of randomization and the date of discontinuation of all protocol treatments (regardless of cause) or date last news for patients alive under treatment.

  5. Treatment safety [ Time Frame: An average of 1 year ]
    Toxicities are evaluated according to NCI-CTC v4.0.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histopathologically or cytologically proven pancreatic adenocarcinoma (on primitive or metastatic lesion)
  • Metastatic disease at a distance
  • At least one measurable lesion according RECIST v1.1 criteria
  • 18 ≤ age ≤ 75 years
  • Life expectancy >12 weeks
  • Performance status WHO < 2
  • No prior chemotherapy : adjuvant chemotherapy by gemcitabine +/- capecitabine is allowed if ended at least 12 months before the inclusion and adjuvant or neo-adjuvant FOLRIFINOX chemotherapy is allowed if ended at least 12 months prior the inclusion
  • Pain well controlled before the inclusion of the patient
  • ANC ≥ 1,500 cells/μL (without the use of hematopoietic growth factors); platelet count ≥ 100,000 cells/μL, hemoglobin ≥ 9 g/dL (blood transfusions is permitted for patients with hemoglobin levels below 9 g/dL)
  • Adequate hepatic function as evidenced by: Serum total bilirubin within normal range for the institution (Serum bilirubin ≤ 1,5 UNL) Biliary drainage allowed for biliary obstruction.
  • Albumin levels ≥ 3.0 g/dL
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN acceptable if liver metastases were present)
  • Normal renal function test (creatinine clearance ≥ 50 ml/min)
  • Normal ECG or ECG without any clinically significant findings
  • Patient able to understand and sign an informed consent
  • Females of child-bearing potential are required to test negative for pregnancy at the time of enrollment based on a urine or serum pregnancy test.
  • Both male and female patients of reproductive potential were required to agree to use a reliable method of birth control, during the study and for 3 months following the last dose of study drug.
  • Patient affiliated to social security
  • Regular follow-up possible

Exclusion Criteria:

  • Uncontrolled brain or meningeal metastasis, or bone metastasis (no need of systematic CT scan)
  • Prior radiation therapy (except if there is at least one measurable target outside irradiation area)
  • Clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > Grade 1
  • History of chronic inflammatory bowel disease
  • Other types of pancreatic tumours, in particular endocrine or acinar cell tumours
  • Ampulloma
  • Gilbert's syndrome
  • Presence of neuropathy > grade 1 according to NCI-CTC
  • History of any second malignancy in the last 5 years; subjects with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they had 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.
  • NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure.
  • Known hypersensitivity to any of the drugs /constituents or non-liposomal irinotecan
  • 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 interferes with the interpretation of the results.
  • Use of CYP3A4/UGT1A inducers/inhibitors
  • Use of strong CYP2C8 inhibitors or inducers, or presence of any other contraindications for nab-paclitaxel or gemcitabine
  • ILD presence
  • Pregnant or breast feeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03693677


Contacts
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Contact: Daniel Gonzalez +33 3.80.39.34.83 daniel.gonzalez@u-bourgogne.fr

Locations
Show Show 36 study locations
Sponsors and Collaborators
Federation Francophone de Cancerologie Digestive
Investigators
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Principal Investigator: Julien Taieb, Pr HEGP - Paris - France
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Responsible Party: Federation Francophone de Cancerologie Digestive
ClinicalTrials.gov Identifier: NCT03693677    
Other Study ID Numbers: PRODIGE 61 - FUNGEMAX
FFCD 1702 ( Other Identifier: FFCD Number )
2017-004309-41 ( EudraCT Number )
First Posted: October 3, 2018    Key Record Dates
Last Update Posted: July 19, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Paclitaxel
Irinotecan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors