Patient
AUTO-PDAC-001 · Algorithm: ALGO-PDAC-METASTATIC-1L
Clinical significance of mutations (ESCAT)
Tumor-board context — the engine does not use these tiers to rank tracks
| Biomarker | Variant | ESCAT | Evidence | Clinical significance | Drugs | Sources |
|---|
| BIO-BRCA1-BRCA2-GERMLINE | BRCA1 germline pathogenic | IA | Molecular evidence option - SRC-CIVIC: Level A (Supports, Sensitivity/Response)
- SRC-CIVIC: Level B (Supports, Better Outcome)
Resistance or avoidance signal | BRCA1 germline pathogenic in metastatic PDAC after ≥16 weeks of platinum without progression: olaparib maintenance improves PFS (POLO, Golan 2019). No OS benefit demonstrated but durable PFS responders observed. ESCAT IA / OncoKB Level 1. | olaparib monotherapy maintenance after platinum-based 1L (FOLFIRINOX or gem-cis) | - SRC-NCCN-PANCREATIC-2025
- SRC-ESMO-PANCREATIC-2024
|
| BIO-BRCA1-BRCA2-GERMLINE | BRCA2 germline pathogenic | IA | Molecular evidence option - SRC-CIVIC: Level A (Supports, Sensitivity/Response)
- SRC-CIVIC: Level B (Supports, Better Outcome)
Resistance or avoidance signal Trial or research option - SRC-CIVIC: Level C (Supports, Sensitivity/Response)
| BRCA2 germline pathogenic in metastatic PDAC: olaparib maintenance after ≥16 weeks platinum without progression (POLO) → mPFS 7.4 vs 3.8 mo. ESCAT IA / OncoKB Level 1. | olaparib monotherapy maintenance after platinum induction (FOLFIRINOX preferred) | - SRC-NCCN-PANCREATIC-2025
- SRC-ESMO-PANCREATIC-2024
|
Primary current-line option
- Indication
- IND-PDAC-METASTATIC-1L-FOLFIRINOX
- Regimen
- FOLFIRINOX
- Drugs + NSZU
- Oxaliplatin (DRUG-OXALIPLATIN) 85 mg/m² · IV day 1 every 14d · IV ✓ NSZU covered
- Irinotecan (DRUG-IRINOTECAN) 180 mg/m² (full); 150 mg/m² in modified FOLFIRINOX (mFOLFIRINOX) · IV day 1 · IV ⚠ NSZU — not for this indication
- Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² · IV day 1 · IV ⚠ NSZU — not for this indication
- 5-Fluorouracil (DRUG-5-FLUOROURACIL) 400 mg/m² IV bolus + 2400 mg/m² CIV over 46h (modified omits bolus to reduce mucositis) · Day 1 bolus, day 1-2 CIV · IV ✓ NSZU covered
- Reason
- Primary current-line option selected by ALGO-PDAC-METASTATIC-1L at step 3; branch-driving red flag: RF-PDAC-FIT-FOR-FOLFIRINOX.
Other current-line alternatives (3 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-PDAC-METASTATIC-1L-NALIRIFOX
- Regimen
- NALIRIFOX
- Drugs + NSZU
- Liposomal irinotecan (DRUG-LIPOSOMAL-IRINOTECAN) 50 mg/m² free base (≈60 mg/m² salt equivalent) · IV over 90 min, day 1 every 14d · IV ✗ Not registered in UA
- Oxaliplatin (DRUG-OXALIPLATIN) 60 mg/m² · IV day 1 every 14d · IV ✓ NSZU covered
- Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² · IV day 1 (after liposomal irinotecan + oxaliplatin) · IV ⚠ NSZU — not for this indication
- 5-Fluorouracil (DRUG-5-FLUOROURACIL) 2400 mg/m² CIV over 46 h · Day 1 starting after leucovorin, every 14d · IV ✓ NSZU covered
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-PDAC-METASTATIC-1L-GEM-NAB-PAC
- Regimen
- Gemcitabine + nab-paclitaxel (MPACT)
- Drugs + NSZU
- Gemcitabine (DRUG-GEMCITABINE) 1000 mg/m² · IV days 1, 8, 15 of 28-d cycle · IV ✓ NSZU covered
- Nab-paclitaxel (albumin-bound paclitaxel) (DRUG-NAB-PACLITAXEL) 125 mg/m² · IV days 1, 8, 15 of 28-d cycle · IV ✓ NSZU covered
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-PDAC-MAINTENANCE-OLAPARIB-BRCA
- Regimen
- Olaparib maintenance (BRCA-mut PDAC post-platinum, POLO)
- Drugs + NSZU
- Olaparib (DRUG-OLAPARIB) 300 mg PO BID continuous · Continuous · PO ⚠ NSZU — not for this indication
- Reason
- Current-line alternative presented for HCP consideration
Why this branch was chosen
Triggers from the patient profile that fired and drove the chosen branch.
Step 3 → branch IND-PDAC-METASTATIC-1L-FOLFIRINOX
- RF-FITNESS-ECOG-FIT: Fit performance status (ECOG 0-1): patient is fully active or restricted in physically strenuous activity but ambulatory and able to carry out light work. Eligible for full-dose chemotherapy and intensive regimens (CHOEP, BEACOPP-escalated, HD-MTX, ASCT consolidation, CAR-T).
SRC-NCCN-BCELL-2025SRC-ESMO-DLBCL-2024
- RF-PDAC-FIT-FOR-FOLFIRINOX ★ winner: Fitness for FOLFIRINOX in metastatic PDAC per PRODIGE-4 / ACCORD-11 inclusion criteria (Conroy NEJM 2011): ECOG 0-1, age ≤75 (≤76 by protocol; convention <=70-75 in real-world), bilirubin ≤1.5× ULN (resolved post-biliary stenting if needed), no significant cardiac comorbidity, adequate hepatic / renal / bone-marrow function. Selects IND-PDAC-METASTATIC-1L-FOLFIRINOX over IND-PDAC-METASTATIC-1L-GEM-NAB-PAC (mOS 11.1 vs 6.8 mo in PRODIGE-4; toxicity tradeoff acceptable in fit patients). Frail / ECOG ≥2 / bilirubin elevated → de-escalate to gem-nab-paclitaxel (MPACT, Von Hoff NEJM 2013).
SRC-NCCN-PANCREATIC-2025SRC-ESMO-PANCREATIC-2024
Pre-treatment investigations
Investigations before treatment start · critical / standard / desired · merged across tracks
| ID | Name | Priority | Category | Where to order | Needed for |
|---|
| TEST-CBC | Complete Blood Count with Differential | Critical | lab | — | all tracks |
| TEST-CMP | Comprehensive Metabolic Panel | Critical | lab | — | standard |
| TEST-CT-CHEST-ABDOMEN-PELVIS | CT chest + abdomen + pelvis with IV contrast | Critical | imaging | — | standard |
| TEST-LFT | Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin) | Critical | lab | — | standard |
| TEST-CT-PET | PET-CT with FDG | Desired | imaging | — | desired (standard) |
| TEST-NGS-COMPREHENSIVE | Comprehensive NGS tumor panel (DNA + RNA, ≥300 genes) | Desired | histology | CSD Lab: M065 | desired (standard) |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Obstructive jaundice / cholangitis in PDAC: total bilirubin ≥3 mg/dL with pancreatic-head mass causing biliary tree dilation, OR active cholangitis (fever + RUQ pain + jaundice). Mandates biliary drainage (ERCP-stent or PTC) BEFORE chemo, which is hepatotoxic and reduces clearance of cytotoxics.
~70% of head-of-pancreas tumors present with jaundice. Biliary stent (preferred metallic for life expectancy >3 mo, plastic for shorter) via ERCP first-line; PTC if ERCP fails. Resolve bilirubin to <2 mg/dL before initiating gem-nab-pac…
RF-PDAC-BILIARY-OBSTRUCTION-CHOLANGITISSRC-NCCN-PANCREATIC-2025SRC-ESMO-PANCREATIC-2024 - Frailty profile precluding FOLFIRINOX in PDAC: ECOG ≥2, OR (age ≥75 + Charlson ≥3), OR composite (age ≥70 + albumin <3.0 + cachexia ≥10% weight loss). Triggers gem-nab-pac (better-tolerated alternative) OR gemcitabine monotherapy OR best supportive care.
ACCORD-11 excluded ECOG ≥2; FOLFIRINOX in real-world frail patients has Grade 3-4 toxicity ~75% + early discontinuation. MPACT trial for gem-nab-pac was more permissive (KPS 70-100); better fit for the borderline-fit patient. Pure BSC for…
RF-PDAC-FRAILTY-AGESRC-NCCN-PANCREATIC-2025SRC-ESMO-PANCREATIC-2024 - Infection-screening gate before PDAC FOLFIRINOX / gem-nab-pac: HBsAg+ / anti-HBc+ (HBV reactivation on dexamethasone-containing regimens), HIV+, OR active cholangitis (post-stent infectious complication — common given biliary instrumentation in head-of-pancreas tumors).
Cholangitis typically post-stenting (~10-20% of plastic stents, lower for metallic). Treat with antibiotics + drainage adjustment; delay chemo until afebrile + bilirubin trending down.
RF-PDAC-INFECTION-SCREENINGSRC-NCCN-PANCREATIC-2025SRC-ESMO-PANCREATIC-2024
CONTRA-AGGRESSIVE
Hard contraindications to escalation
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Standard plan (IND-PDAC-METASTATIC-1L-FOLFIRINOX)
- Do NOT initiate without resolved jaundice (bilirubin <1.5-2 ULN) — irinotecan hepatotoxic
- Do NOT use in PS ≥2 — substantial Grade 3-4 toxicity
- Do NOT skip UGT1A1 testing for high-risk populations (preventable severe diarrhea + neutropenia)
Standard plan (IND-PDAC-METASTATIC-1L-NALIRIFOX)
- Do NOT initiate without resolved jaundice (bilirubin <1.5-2× ULN) — liposomal irinotecan hepatically metabolized
- Do NOT use in PS ≥2 — NAPOLI-3 enrolled only ECOG 0-1; for ECOG 1-2 / older / borderline-fit use gem-nab-pac
- Do NOT skip UGT1A1 testing for high-risk populations — *28/*28 homozygotes need starting-dose reduction (40 mg/m² free base) to prevent severe diarrhea + neutropenia
- Do NOT skip late-diarrhea loperamide prophylaxis education — Grade 3-4 ~20% (higher than gem-nab-pac); patient must have loperamide at home and know the schedule
- Do NOT start without vascular access (PICC or port) for 46-h continuous-infusion 5-FU
- Do NOT confuse liposomal irinotecan with conventional irinotecan — different pharmacokinetics, dosing, and approved indications; ONIVYDE and Camptosar are not interchangeable
Standard plan (IND-PDAC-METASTATIC-1L-GEM-NAB-PAC)
- Do NOT use without addressing biliary obstruction first
- Do NOT continue past Grade 2 functional neuropathy without dose reduction
Aggressive plan (IND-PDAC-MAINTENANCE-OLAPARIB-BRCA)
- Do NOT start without confirmed CR/PR/SD to platinum-induction
- Do NOT skip pre-treatment counseling on long-term MDS/AML risk
- Do NOT use in tumor-only-BRCA without germline confirmation (POLO inclusion was germline)
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · FOLFIRINOX
14-day cycles × 12 cycles (PRODIGE-24 adjuvant); until progression / toxicity (metastatic)
Standard plan
Induction · NALIRIFOX
14-day cycles × Until disease progression or unacceptable toxicity
Standard plan
Induction · Gemcitabine + nab-paclitaxel (MPACT)
28-day cycles × Until progression / unacceptable toxicity
MDT brief
Discussion questions (1, 0 blocking)
MDT talk tree (3 steps)
| # | Owner | Topic | Action |
|---|
| 1 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 2 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
| 3 | molecular_geneticist | Specialist review | Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed. |
Skills (recommended) — for consideration (2)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
- Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
Data quality
Usable with caveats. No critical default-track gap was found, but the MDT should review the listed caveats before final sign-off.
- Biomarker coverage: 1/1 known (100%), 0 missing, 0 default-track gaps
- Unevaluated RedFlags: RF-ATM-CONFIRMED-CARRIER, RF-ATM-FAMILY-HISTORY-SUSPICION, RF-BRCA-CONFIRMED-CARRIER, RF-BRCA-HBOC-FAMILY-HISTORY-SUSPICION, RF-CASCADE-BRCA-FDR-POSITIVE, RF-CASCADE-FAP-FDR-POSITIVE, RF-CASCADE-LYNCH-FDR-POSITIVE, RF-CDKN2A-SPECIFIC-PDAC-CARRIER, RF-CHRONIC-PANCREATITIS-PDAC-PREVENTION, RF-CHRONIC-T2DM-CANCER-RISK-PREVENTION, RF-FAMILIAL-PANCREATIC-CANCER-SYNDROME, RF-FAMMM-CONFIRMED-CARRIER, RF-FAMMM-FAMILY-HISTORY-SUSPICION, RF-FAP-CONFIRMED-CARRIER, RF-FAP-FAMILY-HISTORY-SUSPICION, RF-JPS-CONFIRMED-CARRIER, RF-LIFESTYLE-SMOKELESS-TOBACCO-PREVENTION, RF-LIFESTYLE-SUGARY-BEVERAGES-PREVENTION, RF-LIFESTYLE-TOBACCO-CANCER-PREVENTION, RF-LYNCH-CONFIRMED-CARRIER, RF-LYNCH-FAMILY-HISTORY-SUSPICION, RF-PALB2-CONFIRMED-CARRIER, RF-PALB2-FAMILY-HISTORY-SUSPICION, RF-PAN-ATM-CHEK2-CDK12-PARPI-CANDIDATE, RF-PAN-BRCA-SOMATIC-PARPI-CANDIDATE, RF-PAN-PALB2-PARPI-CANDIDATE, RF-PDAC-BILIARY-OBSTRUCTION-CHOLANGITIS, RF-PDAC-FRAILTY-AGE, RF-PDAC-HIGH-RISK-BIOLOGY, RF-PDAC-INFECTION-SCREENING, RF-PDAC-TRANSFORMATION-PROGRESSION, RF-PEUTZ-JEGHERS-CONFIRMED-CARRIER, RF-PEUTZ-JEGHERS-FAMILY-HISTORY-SUSPICION, RF-VHL-FAMILY-HISTORY-SUSPICION
Technical MDT skill metadata (2/16 activated in this plan)
All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).
| Specialist | skill_id | Version | Last reviewed | Sign-offs | Domain |
|---|
| Cellular therapy specialist (CAR-T) | cellular_therapy_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
| Clinical pharmacist | clinical_pharmacist | v0.1.0 | 2026-04-25 | 0 | clinical_pharmacy |
| Hematologist / oncohematologist | hematologist | v0.1.0 | 2026-04-25 | 0 | hematology_oncology |
| Hematopathologist (lymphoma / leukemia / myeloma) | hematopathologist | v0.1.0 | 2026-04-25 | 0 | hematopathology |
| Infectious disease / hepatology | infectious_disease_hepatology | v0.1.0 | 2026-04-25 | 0 | infectious_diseases |
| Medical oncologist (solid-tumor chemotherapist) | medical_oncologist | v0.1.0 | 2026-04-25 | 0 | solid_oncology |
| Molecular geneticist / molecular oncologist | molecular_geneticist | v0.1.0 | 2026-04-25 | 0 | molecular_oncology |
| Palliative care | palliative_care | v0.1.0 | 2026-04-25 | 0 | palliative_care |
| Pathologist (general) | pathologist | v0.1.0 | 2026-04-25 | 0 | pathology |
| Primary care / family physician | primary_care | v0.1.0 | 2026-04-25 | 0 | primary_care |
| Psycho-oncologist | psychologist | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Radiation oncologist | radiation_oncologist | v0.1.0 | 2026-04-25 | 0 | radiation_oncology |
| Radiologist | radiologist | v0.1.0 | 2026-04-25 | 0 | diagnostic_imaging |
| Social worker / case manager | social_worker_case_manager | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Surgical oncologist | surgical_oncologist | v0.1.0 | 2026-04-25 | 0 | surgical_oncology |
| Transplant specialist (BMT) | transplant_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
Sources cited
- SRC-ESMO-PANCREATIC-2024: ESMO Pancreatic Cancer (2024)
- SRC-NAPOLI-3-WAINBERG-2024: NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial (2023)
- SRC-NCCN-PANCREATIC-2025: NCCN Pancreatic Adenocarcinoma (v.2.2025)
Experimental options (clinical trials)
Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-07-26.
| NCT | Title | Phase | Status | Sponsor | UA | Signals | Eligibility (excerpt) |
|---|
| NCT06079346 | A Study of OT-101 With mFOLFIRINOX in Patients With Advanced and Unresectable or Metastatic Pancreatic Cancer | PHASE2 / PHASE3 | RECRUITING | — | Single country | |
| NCT04146298 | Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer | PHASE1 / PHASE2 | RECRUITING | — | Small N (<50) Surrogate endpoint only Single country | |
| NCT06454383 | Gemcitabine and Leflunomide in Patients With Advanced Unresectable Pancreatic Cancer | PHASE1 | RECRUITING | — | Phase 1 only Small N (<50) Single country | |
| NCT07155525 | Tissue Adhesive Glue Modified Cyanoacrylate (Glubran® 2) in Soft Pancreas | PHASE3 | RECRUITING | — | Single country | |
| NCT07155850 | Early Feasibility Clinical Investigation to Assess YntraDose™ as a Neoadjuvant Treatment for LA-PDAC | NA | RECRUITING | — | Small N (<50) | |
| NCT05984810 | NIR-Fluorescence Guided Surgical Resection of Neoadjuvant Treated Localized Pancreatic Cancer Using SGM-101 | PHASE2 | RECRUITING | — | Small N (<50) Single country | |
| NCT06825546 | Icaritin in Combination With AG in Patients With Previously Untreated Advanced Pancreatic Ductal Adenocarcinoma | PHASE2 | RECRUITING | — | Surrogate endpoint only Single country | |
| NCT04291651 | UCSF PANC Cyst Registry | N/A | RECRUITING | — | Single country | |
| NCT06458712 | Study to Assess Safety, Tolerability and Activity of DSB2455 in Participants With Advanced Malignancies | PHASE1 | RECRUITING | — | Phase 1 only | |
| NCT06005493 | Study of AZD5863 in Adult Participants With Advanced or Metastatic Solid Tumors | PHASE1 / PHASE2 | RECRUITING | — | Surrogate endpoint only | |
Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.
Option availability in Ukraine
Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).
| Option | UA registration | NSZU | Cost orientation | Access pathway |
|---|
| Standard plan FOLFIRINOX (REG-FOLFIRINOX) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan NALIRIFOX (REG-NALIRIFOX) 1/4 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Standard plan Gemcitabine + nab-paclitaxel (MPACT) (REG-GEM-NAB-PAC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Olaparib maintenance (BRCA-mut PDAC post-platinum, POLO) (REG-OLAPARIB-MAINT-PDAC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Trial · NCT06079346 A Study of OT-101 With mFOLFIRINOX in Patients With Advanced and Unresectable or Metastatic Pancreatic Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT04146298 Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06454383 Gemcitabine and Leflunomide in Patients With Advanced Unresectable Pancreatic Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07155525 Tissue Adhesive Glue Modified Cyanoacrylate (Glubran® 2) in Soft Pancreas No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07155850 Early Feasibility Clinical Investigation to Assess YntraDose™ as a Neoadjuvant Treatment for LA-PDAC No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT05984810 NIR-Fluorescence Guided Surgical Resection of Neoadjuvant Treated Localized Pancreatic Cancer Using SGM-101 No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06825546 Icaritin in Combination With AG in Patients With Previously Untreated Advanced Pancreatic Ductal Adenocarcinoma No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT04291651 UCSF PANC Cyst Registry No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06458712 Study to Assess Safety, Tolerability and Activity of DSB2455 in Participants With Advanced Malignancies No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06005493 Study of AZD5863 in Adult Participants With Advanced or Metastatic Solid Tumors No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-07-26.