PANORAMIX : Optimizing 1st-line NALIRIFOX and Exploring Microbiota's Role in 2nd Line Pancreatic Cancer Treatment

NCT07028424 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: PANORAMIX G-116 PRODIGE 105
• Study Type: interventional
• Target: 206
• Locations: 1 country
• Sites: 12

Brief Summary

The main objective of PANORAMIX phase II trial is to optimize first-lie (L1) NALIRIFOX treatment for pancreatic cancer through the implementation of 5-fluorouracil (5-FU) maintenance therapy. Additionally, it aims to investigate the role of antibiotics and microbiota in second-line (L2) treatment.

Conditions

PDAC - Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• 6-month progression-free survival (PFS) rate post randomization Step 1 (R1) in Arm 1A

  To assess the efficacy of a 6-month PFS rate post R1 in patients with metastatic PDAC who received first-line (L1) NALIRIFOX with LV5FU2 (5-FU/leucovorin) maintenance strategy during Step 1 (Arm 1A).

  6 months

Secondary Outcomes (13)

• Progression-free survival first-line (PFS-L1) post randomization Step 1 (R1) in Arm 1A and in Arm 1B

  up to 5 years

• Progression-free survival (PFS) post NALIRIFOX reintroduction (PFS-reintro) in Arm 1A

  up to 5 years

• Overall survival post randomization Step 1 (OS-R1) in Arm 1A and in Arm 1B

  up to 5 years

• Overall response rate of first-line (ORR-L1) at 4 months in Arm 1A and in Arm 1B

  4 months

• Overall response rate post NALIRIFOX reintroduction (ORR-RI) in Arm 1A

  up to 5 years

Study Arms (4)

STEP 1 - Experimental Arm 1A : First-line NALIRIFOX with LV5FU2 [5-FU/leucovorin] maintenance)

EXPERIMENTAL

NALIRIFOX (NAL-IRI + 5FU/LV + oxaliplatin; 8 cycles) followed by LV5FU2 maintenance administered every 14 days (2 weeks) followed by NALIRIFOX reintroduction (for maximum 8 cycles) followed by LV5FU2 maintenance

Drug: Nal-IRI; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-Fluorouracil

STEP 1 - Arm 1B: NALIRIFOX

ACTIVE COMPARATOR

NALIRIFOX until disease progression or unacceptable toxicity

Drug: Nal-IRI; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-Fluorouracil

STEP 2 - Arm 2A: Gemcitabine +/- paclitaxel + ciprofloxacin

EXPERIMENTAL

Gemcitabine: 1,000 mg/m2 intravenously (IV) over 30 minutes weekly on days 1, 8, 15 of each 28-days cycle. +/- Paclitaxel 80 mg/m2 weekly on days 1, 8, 15 of each 28-days cycle (at the discretion of investigator). Ciprofloxacin (6 capsules/cycle, withhold if gemcitabine is not administered): 500 mg twice daily (morning and evening; 12 hours should elapse between two doses) on days 1, 8, 15 (on day of gemcitabine infusion) for a maximum of 6 months.

Drug: Ciprofloxacin; Drug: Paclitaxel; Drug: Gemcitabine

STEP 2 - Arm 2B: Gemcitabine +/- paclitaxel + placebo

ACTIVE COMPARATOR

Gemcitabine: 1,000 mg/m2 intravenously (IV) over 30 minutes weekly on days 1, 8, 15 of each 28-days cycle. +/- Paclitaxel 80 mg/m2 weekly on days 1, 8, 15 of each 28-days cycle (at the discretion of investigator). Placebo (6 capsules/cycle, withhold if gemcitabine is not administered): 500 mg twice daily (morning and evening; 12 hours should elapse between two doses) on days 1, 8, 15 (on day of gemcitabine infusion) for a maximum of 6 months.

Drug: Paclitaxel; Drug: Gemcitabine; Other: Placebo

Interventions

Nal-IRI DRUG

NAL-IRI 50 mg/m2, administered over 80-100 minutes, on day 1 of a 14-days cycle

Also known as: iposomal irinotecan

STEP 1 - Arm 1B: NALIRIFOX; STEP 1 - Experimental Arm 1A : First-line NALIRIFOX with LV5FU2 [5-FU/leucovorin] maintenance)

Ciprofloxacin DRUG

6 capsules/cycle : 500 mg twice daily on days 1, 8, 15 (on day of gemcitabine infusion) for a maximum of 6 months

STEP 2 - Arm 2A: Gemcitabine +/- paclitaxel + ciprofloxacin

Paclitaxel DRUG

80 mg/m2 weekly on days 1, 8, 15 of each 28-days cycle (at the discretion of investigator)

STEP 2 - Arm 2A: Gemcitabine +/- paclitaxel + ciprofloxacin; STEP 2 - Arm 2B: Gemcitabine +/- paclitaxel + placebo

Gemcitabine DRUG

1,000 mg/m2 intravenously (IV) over 30 minutes weekly on days 1, 8, 15 of each 28-days cycle

STEP 2 - Arm 2A: Gemcitabine +/- paclitaxel + ciprofloxacin; STEP 2 - Arm 2B: Gemcitabine +/- paclitaxel + placebo

Oxaliplatin DRUG

60 mg/m2 (starting 2 hours later, administered over 110-130 minutes) on day 1

STEP 1 - Arm 1B: NALIRIFOX; STEP 1 - Experimental Arm 1A : First-line NALIRIFOX with LV5FU2 [5-FU/leucovorin] maintenance)

Leucovorin DRUG

As part of NALIRIFOX -for 8 cycle treatment: (L + D racemic form) 400 mg/m2 on day 1 (equivalent to 200 mg/m2 levoleucovorin) (starting 30 minutes after oxaliplatin, administered over 25-35 minutes) As part of LV5FU2 maintenance treatment: 400 mg/m2 IV infusion over 30 min on day 1 (equivalent to 200 mg/m2 levoleucovorin). LV could be administered over 2 hours to oxaliplatin according to The National Thesaurus of Digestive Oncology (TNCD) https://www.snfge.org/sites/www.snfge.org/files/tncd/2024-05/tncd\_chap-09-cancer-pancre%CC%81as\_2024-05-17\_1.pdf, at investigator's discretion

STEP 1 - Arm 1B: NALIRIFOX; STEP 1 - Experimental Arm 1A : First-line NALIRIFOX with LV5FU2 [5-FU/leucovorin] maintenance)

5-Fluorouracil DRUG

As part of NALIRIFOX -for 8 cycle treatment: 2400 mg/m² IV initiated on day 1, with continuous infusion over 46 hours (no bolus infusion with 5-FU) As part of LV5FU2 maintenance treatment: 400 mg/m2 bolus over 10 min then 2,400 mg/m2 IV infusion over 46h

STEP 1 - Arm 1B: NALIRIFOX; STEP 1 - Experimental Arm 1A : First-line NALIRIFOX with LV5FU2 [5-FU/leucovorin] maintenance)

Placebo OTHER

6 capsules/cycle : 500 mg twice daily (morning and evening; 12 hours should elapse between two doses) on days 1, 8, 15 (on day of gemcitabine infusion) for a maximum of 6 months

STEP 2 - Arm 2B: Gemcitabine +/- paclitaxel + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations (only after interim analysis at Step 2 for patients who were not randomized in first randomization \[R1\]),
• Age ≥18 years old. STEP 1: The patient over 75 years of age is eligible only if the patient's G8 score (G8 questionnaire) is \> 14,
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1,
• Histologically or cytologically proven PDAC,
• ≥1 measurable lesion according to RECIST v 1.1 (Computed tomography thorax-abdomen-pelvis \[TAP-CT\] scan ≤ 4 weeks), Note: abdominal magnetic resonance imaging (MRI) is allowed (e.g., in case of contra-indication to CT scan contrast injection) provided that this imaging modality is used consistently throughout the tumor evaluations,
• Availability of archival tissue samples for exploratory research. Step 2: can be the same as in Step 1 or it can be newly obtained sample,
• Adequate organ function, obtained within 21 days prior to randomization of study treatment, as defined by the following:
• Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤3 x upper limit of normal (ULN; ≤ 5 x ULN in case of liver metastases) - STEP 2, if paclitaxel administration,
• Total serum bilirubin \< 1.5 x ULN (STEP 2, if paclitaxel administration),
• Serum albumin ≥ 28 g/L,
• Hemoglobin ≥ 9.0 g/dl,
• Absolute neutrophil count (ANC) ≥ 2 x 10\^9L,
• Platelets - STEP 1: ≥ 150 x 10\^9L; STEP 2: ≥ 100 x 10\^9L,
• Creatinine clearance ≥ 50 mL/min (Modification of the Diet in Renal Disease \[MDRD\]),
• Evidence of post-menopausal status or negative serum pregnancy test within 7 days before starting study treatment for female pre- menopausal patients. Women of childbearing potential (WOCBP) should use effective contraception during study treatment and: 1 month (paclitaxel), 6 months (5FU, LV), 7 months (NAL-IRI), 15 months (oxaliplatin), and 6 months (gemcitabine+/-paclitaxel and ciprofloxacin/placebo) after the patient's last dose of treatment. Males who are fertile should use effective contraception during study treatment and 4 months (NAL-IRI), 6 months (5-FU, LV), 12 months (oxaliplatin), and 6 months (gemcitabine+/-paclitaxel and ciprofloxacin/placebo) after the patient's last dose of treatment.

You may not qualify if:

• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study,
• History of allogenic organ transplantation or active autoimmune, connective tissue disorder, or inflammatory disease requiring systemic treatment,
• Diagnosis of any second malignancy that required any treatment within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri,
• History of idiopathic pulmonary fibrosis, interstitial lung disease (ILD), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening (TAP-CT-scan),
• Current systemic steroid therapy (\>10 mg daily dose of prednisone or equivalent; minimal wash-out of 1 week \[7 days\]) or immunosuppressive therapy,
• Prior radiotherapy treatment to more than 30% of the bone marrow or a wide field of radiation within 4 weeks (30 days) prior to the first dose of study drug,
• Major surgical procedure (as defined by the Investigator) within 4 weeks (30 days) prior to the first dose of trial treatment (Step 1 and Step 2), Note: Local surgery of isolated lesions for palliative intent is acceptable,
• Uncontrolled central nervous system metastases and/or carcinomatous meningitis,
• Uncontrolled massive pleural effusion or massive ascites,
• Uncontrolled intercurrent illness, including but not limited to, symptomatic congestive heart failure or coronary disease, peripheral artery disease, severe chronic obstructive pulmonary disease, decompensated cirrhosis, serious chronic gastrointestinal conditions (e.g. bleeding, inflammation, occlusion, malabsorption syndrome, ulcerative colitis, gastrointestinal ulceration, infection or sepsis, inflammatory bowel disease or partial bowel obstruction) associated with diarrhea, or geographical/social/ psychiatric illness situations that would limit compliance with study requirement and study follow-up, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent,
• History or current evidence of any condition, therapy, laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the participant in the opinion of the treating investigator,
• QT/QTc interval \>470 ms (for women) and \> 450 ms (for men), previous ventricular arrhythmia, known or suspected long-QT syndrome, Note: Caution is required when using medicinal products with human thymidine kinase substrates, e.g. zidovudine and other drugs known to prolong the QTc interval (exhaustive list on https: //www.crediblemeds.org.")
• Known or suspected allergy or hypersensitivity to any of the study drugs or any of the study drug excipients,
• Active bacterial, viral, or fungal infection requiring systemic therapy, including tuberculosis, hepatitis B (HBV, known positive HBV surface antigen \[HbsAg\] result), hepatitis C (HBC, with positive RNA), or human immunodeficiency virus (HIV positive 1/2 antibodies), Note: Patients with past HBV infection or resolved HBV infection (defined as having a negative HbsAg test and a positive hepatitis B core antigen \[HBc\] antibody test) are eligible; patients with previously treated and cured HCV infection (negative RNA) are also eligible,
• Live vaccine administration within 4 weeks (30 days) prior to the first dose of study treatment,

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead
• Servier: collaborator

Study Sites (12)

CHU de Besançon

Besançon, France

Location

CHU de Grenoble

La Tronche, France

Location

CHU de Lille

Lille, France

Location

Institut Curie

Paris, France

Location

Pitié Salpêtrière Hospital

Paris, France

Location

Saint-Antoine Hospital

Paris, France

Location

CHU de Poitiers

Poitiers, France

Location

CHU de Reims

Reims, France

Location

Institute Curie

Saint-Cloud, France

Location

CHU de Saint Etienne

Saint-Etienne, France

Location

Hôpital d'Instruction des Armées Bégin

Saint-Mandé, France

Location

Paul Brousse Hospital

Villejuif, France

Location

MeSH Terms

Interventions

irinotecan sucrosofate; Ciprofloxacin; Paclitaxel; Gemcitabine; Oxaliplatin; Leucovorin; Fluorouracil

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones

Study Officials

• Cindy NEUZILLET, MD

  Institute Curie, Versailles Saint-Quentin University, Saint-Cloud,

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cindy NEUZILLET, MD

CONTACT

+33 (0) 1 47 11 15 15; cindy.neuzillet@curie.fr

Marie-Line GARCIA LARNICOL, MD

CONTACT

+33 (0) 1 40 29 85 04; marie-line.garcia-larnicol@gercor.com.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Only STEP 2 of the study is masked; a double-blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized, non-comparative two-step study in patients with metastatic PDAC. STEP 1 (main objective) This is a two-arm, open-label, randomized (2:1), non-comparative single stage phase II study to assess the efficacy of 5-FU-based maintenance after NALIRIFOX initiation (Arm 1A) versus standard NALIRIFOX in patients with metastatic PDAC (Arm 1B). STEP 2 (secondary exploratory objective) This is a two-arm, double-blinded, randomized (1:1), non-comparative, two-stage phase II with ciprofloxacin + gemcitabine-based chemotherapy (gemcitabine +/- paclitaxel) regimen (Arm 2A) versus gemcitabine-based chemotherapy (gemcitabine +/- paclitaxel) regimen + placebo (Arm 2B)

Study Record Dates

• First Submitted: June 11, 2025
• First Posted: June 19, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (12)