A Guide to Clinical Trials in Pancreatic Cancer Pancreatic Cancer

PRACTICE AID

A Guide to Clinical Trials in Pancreatic Cancer Pancreatic Cancer www.letswinpc.org

• Clinical trials can be an important therapeutic tool for the treatment of pancreatic cancer • Let’s Win offers information for patients on therapies being tested in clinical trials: letswinpc.org/clinical-trials • Others include Pancreatic Cancer Action Network (clinicaltrials.pancan.org) and clinicaltrials.gov.

Clinical Trials by Phase

Phase 1: Is it Safe? Phase 3 • First in human; small numbers of patients Is it Better Than What Is Already Available? • Focus is safety • Larger number of patients (100s) • Determine what the drug does to the body and • Randomized what the body does with the drug • Compared with standard approved therapies • Determine the maximum tolerated dose (MTD) • May be blinded or double-blinded • No placebo • May use a placebo • Often available in community oncology practices

Phase 2 : Does It Work? • Further tests MTD frequently in specific cancers Phase 4: • Average of 25 to 100 patients Testing Factors After Approval • Ongoing monitoring for safety • Study of approved drug • No placebo • Ongoing safety, other indications, etc • Trend is small “proof of principle” trials; 25 to 35 patients

A Guide to Clinical Trials in Pancreatic Cancer Pancreatic Cancer www.letswinpc.org

Ongoing Trials of Immunotherapy in Metastatic Pancreatic Cancer

NCT04377048 NCT02754726 Phase Nivolumab Adding on Gemcitabine/S-1 Nivolumab + cisplatin + paricalcitol 2 Recruiting TEDOPAM (NCT03806309) Not Yet Recruiting

Frontline Maintenance Therapy With OSE2101 Vaccine ± Nivolumab, or FOLFIRI, Active, Not Recruiting After Induction Therapy With FOLFIRINOX

COMBAT/KEYNOTE-202 NCT03006302 NCT01174121 (NCT02826486) Phase Epacadostat + Pembrolizumab Tumor Infiltrating Lymphocytes BL-8040 + Pembrolizumab ± Irinotecan 2 + CRS-207 ± GVAX Pancreas Vaccine + Pembrolizumab

reated + Leucovorin + 5-FU

NCT0319025 NCT03264404 NCT03250273 CRS-207 + Nivolumab + Ipilimumab Azacitidine + Pembrolizumab Entinostat + Nivolumab + GVAX/Cy Previously T NCT0310443 NCT04361162 CheckPAC (NCT02866383) Nivolumab + Ipilimumab Nivolumab + Ipilimumab + Radiation Nivolumab ± Ipilimumab (MSS or MSI-High Disease) (MSS Disease) With Radiotherapy

DOME (NCT04262388) Durvalumab + Oleclumab

NCT03816358 Morpheus-Pancreatic (NCT03193190) Phase Anetumab Ravtansine + Nivolumab Atezolizumab-Based Combinations 1/2 ± Ipilimumab or Gemcitabine

NCT02757391 NCT04050085 Phase NCT04007744 CD8+ T Cell Therapy SD-101, Nivolumab, 1 Sonidegib and Pembrolizumab and Pembrolizumab and Radiation Therapy

A Guide to Clinical Trials in Pancreatic Cancer Pancreatic Cancer www.letswinpc.org

Other Ongoing Trials in Metastatic Pancreatic Cancer

NCT03140670 Parpvax (NCT03404960) Recruiting Phase First-Line Maintenance Rucaparib Phase First-Line Maintenance Niraparib Not Yet Recruiting 2 1/2 (BRCA1-, BRCA2-, or PALB2-Mutated Patients) + Ipilimumab or Nivolumab Active, Not Recruiting in First-Line Maintenance PARP Inhibitors

FUNGEMAX (NCT03693677) NCT01954992 Phase 5-FU/LV + Nal-IRI, Nab-paclitaxel + Gemcitabine Sequential Glufosfamide vs 5-FU 2 vs 5-FU/LV + Nal-IRI vs Nab-paclitaxel + Gemcitabine

Agents NCT03086369

First-Line: Phase Olaratumab + Nab-paclitaxel 1/2 Other Emerging + Gemcitabine

Phase NCT02890355 NCT02677038 NCT03682289 2 FOLFIRI or mFOLFIRI and Veliparib Olaparib (BRCA-ness Phenotype) Olaparib + AZD6738

NIRA-PANC NCT02498613

Inhibitors (NCT03553004) Previously Olaparib + Cediranib

Treated: PARP Niraparib After Previous Chemotherapy

Phase NCT03126435 3 EndoTAG-1 + Gemcitabine

DESTINY-PanTumor02 Phase (NCT04482309) NAPAN NCT02921737 2 Trastuzumab Deruxtecan (NCT03986294) TAS-102 in HER2-Expressing Tumors Nal-IRI + S1

NCT03368963

Previously Treated: Phase Nal-IRI + TAS-102 Other Emerging Agents 1/2

A Guide to Clinical Trials in Pancreatic Cancer Pancreatic Cancer www.letswinpc.org

Ongoing Trials of Immunotherapy in Resectable and Locally Advanced Pancreatic Cancer

NCT03727880 NCT03563248 Recruiting Phase Pembrolizumab + Defactinib Neoadjuvant Losartan + Nivolumab + 2 (Neoadjuvant/Adjuvant) FOLFIRINOX + SBRT Not Yet Recruiting

Disease Active, Not Recruiting in Resectable Immunotherapy NCT03572400 Neoadjuvant CCRT With Gemcitabine + Durvalumab Adjuvant Gemcitabine/ Durvalumab

UVA-PC-PD101 (NCT02305186) Phase Neoadjuvant Pembrolizumab 1/2 ± Chemoradiotherapy

MIMIPAC NCT03161379 NCT02648282 (NCT04156087) GVAX + CY + Nivolumab + SBRT Phase CY + Pembrolizumab Durvalumab + Tremelimumab in Borderline-Resectable 2 + GVAX + SBRT + Microwave Ablation for Unresectable Disease Pancreatic Cancer Locally Advanced Pancreatic Cancer Locally Advanced Immunotherapy in

A Guide to Clinical Trials in Pancreatic Cancer Pancreatic Cancer www.letswinpc.org

Other Ongoing Trials in Resectable and Locally Advanced Pancreatic Cancer

SWOG-1505 (NCT02562716) NCT02481635 NEONAX (NCT02047513) Phase Neoadjuvant Nab-paclitaxel + Neoadjuvant Gemcitabine Neoadjuvant Plus Adjuvant or Only 2 Gemcitabine or FOLFIRINOX + Nab-paclitaxel + Radiation Adjuvant Nab-paclitaxel + Gemcitabine

NEOLAP (NCT02125136) NCT02723331 NEO-Nal-IRI Neoadjuvant Nab-paclitaxel + Perioperative Nab-paclitaxel (NCT03483038) Gemcitabine vs Nab-paclitaxel + + Gemcitabine Neoadjuvant Nal-IRI + FOLFOX Gemcitabine + FOLFIRNOX in Resectable Disease Other Emerging Therapies

PANOVA-3 (NCT03377491) LAPIS (NCT03941093) NCT01926197 Phase TTFields + Nab-paclitaxel Pamrevlumab + Nab-paclitaxel + FOLFIRINOX ± SBRT 3 + Gemcitabine Gemcitabine

TIGer-PaC (NCT03257033) DIRECT (NCT03899636) Intra-arterial Gemcitabine NanoKnife System

NCT03861702 NCT03077685 Phase Recruiting Nal-IRI + oxaliplatin + LV + 5-FU Intratumoral Sterile Nanoparticulate 2 (NALIRIFOX) Paclitaxel Not Yet Recruiting Active, Not Recruiting Locally Advanced Disease

Other Emerging Therapies in NCT02210559 Phase FG-3019 + Nab-paclitaxel 1/2 + Gemcitabine

A Resource for Clinical Professionals to Guide Pancreatic Cancer Patient Discussions on Pancreatic Cancer www.letswinpc.org

Types of Pancreatic Cancer1-3 Disease Symptoms1-4 • Ductal adenocarcinoma (most common) Liver • Jaundice • Nausea and vomiting • Acinar cell carcinoma • Pain in the back or abdomen • Acute pancreatitis attacks • Intraductal papillary mucinous carcinoma Stomach • Pancreatoblastoma • Fatigue • New onset diabetes • Neuroendocrine Gallbladder • Loss of appetite/unintended • Diarrhea 1-3 Lymph Normal Function of the Pancreas nodes weight loss • Produces digestive enzymes (exocrine cells) Pancreas • Helps to regulate blood sugar (endocrine cells)

CLINICAL STAGING5,6 SYMPTOMS AND MANAGEMENT7-9

Liver Physical No detectable Resectable pancreatic cancer can be evidence of Stomach surgically removed Abdominal pain VTE spread to areas • NSAIDs • Low MW heparin Gallbladder • Tumors may lie within the pancreas outside of the tissue; • Opioids or extend beyond, but no involvement Fatigue removed during • Celiac plexus nerve block • Nutrition, exercise, sleep Lymph nodes of critical arteries or veins surgery Cancer cells Biliary obstruction & jaundice • Psychological support Pancreas • Biliary stent; endoscopic or external • Thyroid function Gastric outlet obstruction • Testosterone levels in men Liver Locally advanced, unresectable; treatment • Enteral stent Exocrine insu ciency • Gastrojejunostomy • Pancreatic enzymes at the No evidence includes chemotherapy, clinical trials, Stomach beginning of each meal/snack of spread to and radiation Gallbladder other areas • Con ned to area around pancreas; of the body Lymph nodes intertwined with blood vessels; invasion Diet & Nutrition Psychosocial Cancer cells Pancreas of surrounding organs Anorexia/weight loss Anxiety, depression, and suicide risk • Registered dietitian • Psychosocial support • Appetite stimulants • Referral for counselling Liver Metastatic pancreatic cancer; chemotherapy Nausea • Antidepressant Involved organs can be used across multiple lines of Stomach • Antiemetics may include the liver therapy; clinical trials are an important • Add promotility agent if evidence and lungs; other areas Gallbladder treatment option of the abdomen may of gastroparesis be aected Lymph nodes • Has spread beyond the area of the Dehydration Pancreas Cancer cells pancreas and involves other organs • IV hydration

A Resource for Clinical Professionals to Guide Pancreatic Cancer Patient Discussions on Pancreatic Cancer www.letswinpc.org

ANSWERING PATIENT QUESTIONS ABOUT CLINICAL TRIALS10-13

Your patient with pancreatic cancer may have questions about clinical trials. This guide provides advice for answering some of the questions patients commonly ask about clinical trials. Additional resources for patients can be found in the references.

What is a clinical trial? Will I get the placebo?

A clinical trial is a research study involving human volunteers to help determine if new Not all clinical trials have a placebo group. You should ask if a trial you are considering has a treatments are safe, e ective, or better in some way than standard treatments. placebo group and what the chances are that you may be in the placebo group. Placebos are given with the best available treatment for your cancer. If there is no treatment for your cancer, you will receive the best supportive care plus placebo. What are the bene ts? What is informed consent? You may have access to new treatments which are not available outside of a clinical trial. If the treatment is e ective, you may be one of the rst to benet. During the trial you Every patient in a clinical trial is given an informed consent form that they review with a member will be closely monitored. Patients who participate in clinical trials help advance of the clinical team. After reading the document and obtaining answers to any questions you may cancer treatments. have, you will be asked to sign the document.

Can I leave a clinical trial? What are the risks? Yes. You may leave at any time, for any reason. All clinical trials have some risk. The new treatment may not be better than the current standard of care or may help only some of the patients. Side e ects of the new treatment might be worse than expected or than the standard treatment. Because patients in clinical Should I enroll in a clinical trial? trials are closely monitored they may have more doctor visits and more tests to determine the e ects of treatment. Only the patient can make this decision. Clinicians can provide information and resources to the patient and caregivers and answer questions. Clinical professionals may also search for and help determine eligibility of a patient for a clinical trial.

A Resource for Clinical Professionals to Guide Pancreatic Cancer Patient Discussions on Pancreatic Cancer www.letswinpc.org

COVID-19: GUIDANCE ON HOW TO COMMUNICATE TO PATIENTS WITH CANCER14

What You Might Say

“If it’s OK, I’d like to try to explain why we are doing things this way.” • We expect/have a surge in people with COVID-19 here • The number of people needing care will soon be/is greater than resources (hospital beds, doctors, and medical Context: Sharing the “why” supplies) to reduce patient distress • This has impacted how we are treating our patients with cancer during this difficult time • As more patients with COVID-19 come into the health system, we need to think carefully about how to: – Take the best care of you and optimize your cancer treatment – Protect you and others from getting the virus

“I have talked with leaders in the cancer center and my colleagues and thought hard about your case. I/we think the best plan would be [your recommendation].” Consideration: Highlight your process and show you’re thinking “It sounds like you’re scared about delaying your treatment. I want you to know that I want what’s best for you. I wish we about patients’ cases could have continued our original plan/schedule." • I believe this new plan is a safe/the best way to manage your care over the next few months • I believe this new plan will reduce your risk of being exposed to the virus • I believe this new plan will help keep your immune system strong while the virus is spreading in the community

"Part of the difficulty is the uncertainty of how long this will last. Through all of this, I will be your doctor, and we will work Commitment: Express your together to get you the best possible care." commitment to ongoing care • The best way for us to stay in touch would be [method] and suggest action steps • The best things you can do to stay safe are [link to patient resources] • The cancer center also has more resources [link to patient resources]

MW: molecular weight; NSAID: nonsteroidal anti-inflammatory drug; VTE: venous thromboembolism. 1. https://www.lustgarten.org/get-informed/quick-facts-a-pancreatic-cancer-infographic. 2. https://www.cancer.gov/types/pancreatic/hp/pancreatic-treatment-pdq. 3. https://www.pancan.org/facing-pancreatic-cancer. 4. https://letswinpc.org/symptoms. 5. https://www.cancer.net/cancer- types/pancreatic-cancer/stages. 6. https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. 7. https://www.nccn.org/patients/resources/life_with_cancer/managing_symptoms/fatigue.aspx. 8. Akizuki N et al. Jpn J Clin Oncol. 2016;46:71-77. 9. Laquente B et al. Clin Transl Oncol. 2017;19:1293-1302. 10. https://www.cancer.gov/about-cancer/treatment/clinical-trials. 11. https://www.pancan.org/facing-pancreatic-cancer/treatment/treatment-types/clinical-trials/common-concerns-about-clinical-trials. 12. https://www.cancer.org/treatment/treatments-and-side-effects/ clinical-trials/what-you-need-to-know/who-does-clinical-trials.html. 13. https://www.cancer.net/research-and-advocacy/clinical-trials. 14. https://www.rogelcancercenter.org/cancer-patients-and-covid. Access the activity, “Making Headway Toward Better Outcomes in Pancreatic Cancer: The Oncology Nurse as a Leader and Advocate for Patients in an Era of Advances in Care and Research,” at PeerView.com/USV40 PRACTICE AID Algorithm of Systemic Treatment Selection for Metastatic Pancreatic Cancer Pancreatic Cancer1 www.letswinpc.org

Patients With Good PS

First Line Options

• Preferred Regimens – Nab-paclitaxel + gemcitabine – FOLFIRINOX or mFOLFIRINOX • BRCA1/2 or PALB2 Mutations – FOLFIRINOX or mFOLFIRINOX – Gemcitabine + cisplatin

If stable disease If disease progression Maintenance Options* Second Line Options

• Nab-paclitaxel + gemcitabine (modified Selection is based on prior fluoropyrimidine-based schedule) or gemcitabine-based therapy • Gemcitabine • Nal-IRI + 5-FU/LV • Preferred: • FOLFIRI, (m)FOLFIRINOX, FOLFOX, OFF, – FOLFIRI capecitabine ± oxaliplatin, continuous 5-FU • Other Recommended Regimens: • Gemcitabine – FOLFOX • Gemcitabine + nab-paclitaxel – Capecitabine • Gemcitabine + cisplatin (only for known • Previous Platinum-Based CTX and Germline BRCA1/2 mutations) BRCA1/2 mutations – Olaparib

Maintenance Therapy

Maintenance therapy is used to extend the time that a patient’s cancer Targeted Therapy Options will remain stable, or without tumor progression, after initial treatment. Clinical trials have shown that maintenance therapy in patients with • MSI-H/dMMR Tumors: pancreatic cancer is feasible, safe, and can significantly prolong the – Pembrolizumab time to disease progression. The NCCN guidelines recommends that patients with metastatic disease who have response or stable disease • TMB-High Tumors: after 4-6 months of chemotherapy may undergo maintenance therapy. – Pembrolizumab • NTRK Fusion-Positive Tumors: – Larotrectinib Germline Testing – Entrectinib The NCCN recommends germline testing for any patient with confirmed • BRCA1/2-mutant Tumors: pancreatic cancer and tumor/somatic gene profiling for patients with – Olaparib in frontline locally advanced/metastatic disease who are candidates for anti-cancer maintenance setting therapy, to identify actionable mutations that could provide a personalized treatment recommendation for the patient.

Access the activity, “Making Headway Toward Better Outcomes in Pancreatic Cancer: The Oncology Nurse as a Leader and Advocate for Patients in an Era of Advances in Care and Research,” at PeerView.com/USV40 PRACTICE AID Algorithm of Systemic Treatment Selection for Metastatic Pancreatic Cancer Pancreatic Cancer1 www.letswinpc.org

Patients With Poor PS

First Line Options

• Gemcitabine: 1,000 mg/m2 over 30 minutes, weekly for 3 weeks every 28 days • Gemcitabine: fixed-dose-rate (10mg/m2/min) may substitute for gemcitabine over 30 minutes • Capecitabine • Continuous infusion 5-FU • Molecular-Based Treatment Options – MSI-H/dMMR Tumors: Ø Pembrolizumab – NTRK Fusion-Positive Tumors Ø Larotrectinib Ø Entrectinib

Second Line Options

• Gemcitabine:1,000 mg/m2 over 30 minutes, weekly for 3 weeks every 28 days • Gemcitabine: fixed-dose-rate (10mg/m2/min) may substitute for gemcitabine over 30 minutes • Capecitabine • Continuous infusion 5-FU • Molecular-Based Treatment Options – MSI-H/dMMR Tumors Ø Pembrolizumab – TMB-High Tumors Ø Pembrolizumab – NTRK Fusion-Positive Tumors Ø Larotrectinib Ø Entrectinib

BRCA1/2: breast cancer 1/2; CTX: cerebrotendinous xanthomatosis; dMMR: mismatch repair deficient; MSI-H: microsatellite instability high; PALB2: partner and localizer of BRCA2. 1. https://www.nccn.org/professionals/physician_gls/pdf/pancreatic_blocks.pdf. Access the activity, “Making Headway Toward Better Outcomes in Pancreatic Cancer: The Oncology Nurse as a Leader and Advocate for Patients in an Era of Advances in Care and Research,” at PeerView.com/USV40 PRACTICE AID Emerging Modalities and New Targeted Therapies in Metastatic Pancreatic Cancer Pancreatic Cancer www.letswinpc.org

Molecular Mechanism of PARP Inhibition1,2

Pt Pt Platinum PARP PARP chemotherapy inhibitor Pt PARP In icts DNA PARP Replication damage via upregulation Inhibition for collapse adducts and Base-excision of PARP Double-strand DNA Pt repair of DNA Disables DNA DNA break crosslinking damage base-excision Pt repair

RecombinationBRCA1 repair BRCA2 Cell survival Cell death

NA damage PARP

PAR

Chains of PAR NA

Nicotinamide PAR

Repair enzymes

Access the activity, “Making Headway Toward Better Outcomes in Pancreatic Cancer: The Oncology Nurse as a Leader and Advocate for Patients in an Era of Advances in Care and Research,” at PeerView.com/USV40 PRACTICE AID Emerging Modalities and New Targeted Therapies in Metastatic Pancreatic Cancer Pancreatic Cancer www.letswinpc.org

Adverse Events Reported in the Phase 3 POLO Trial of Olaparib3,4

Common Adverse Effects Serious Adverse Effects

Nausea, fatigue, vomiting, abdominal pain, anemia, diarrhea, dizziness, neutropenia, leukopenia, Risk of hematologic toxicity, influenza, respiratory tract infection, including myelodysplastic arthralgia/myalgia, dysgeusia, syndrome or acute myeloid headache, dyspepsia, decreased leukemia; pneumonitis; and appetite, constipation, stomatitis, embryo–fetal toxicity. dyspnea, and thrombocytopenia

Treatment-Related Issues Nurses Should...

Monitor and consider interruption or dose reduction (Recommended Common adverse events dose reduction is 250 mg orally twice daily)

Determine if the patient is also taking medications that are strong or Olaparib is metabolized moderate CYP3A inhibitors, as these via the can increase the circulating levels of cytochrome P-450 (CYP) olaparib: Either co-administration 3 A pathway should be avoided, or the olaparib dose should be decreased

Reduce olaparib dosage to Moderate renal impairment 200 mg orally twice daily

Access the activity, “Making Headway Toward Better Outcomes in Pancreatic Cancer: The Oncology Nurse as a Leader and Advocate for Patients in an Era of Advances in Care and Research,” at PeerView.com/USV40 PRACTICE AID Emerging Modalities and New Targeted Therapies in Metastatic Pancreatic Cancer Pancreatic Cancer www.letswinpc.org

Tumor Treating Fields (TTFields): A New Modality for Treating Cancer

TTFields are alternating electric TTFields therapy is What are fields that are tuned to specific How do administered via a wearable TTFields? TTFields work? frequencies to disrupt cell division, medical device with transducer inhibiting tumor growth and causing arrays, which is placed based affected cancer cells to die. on the location of the tumor.

Effects on Cells Are Frequency Specific and Inversely Related to Cell Size5-8 TTFields Frequencies

ormal intestine reast cancer Mesothelioma Pancreatic cancer kHz kHz kHz kHz

CC varian cancer M CC kHz kHz kHz kHz

Integrating TTFields Therapy Into Clinical Practice: Factors to Consider

Training on TTFields Device Patient Factors

• Device support specialists/nurses provide training in the patients’ homes • Positioning of transducer arrays is individualized for • Comprehensive initial visit: discussion of array every patient placement, equipment use, and skin care • Patient education and compliance with wearing the • Monthly visits thereafter: downloading of compliance device are critical reports that show patients how many hours of • Continuous monitoring is necessary therapy they received each day • Phone or in-person support as needed

BRCA: breast cancer gene; GABA: gamma-aminobutyric acid; GBM: glioblastoma multiforme; NAD: nicotinamide adenine dinucleotide; NSCLC: non–small cell lung cancer; PAR: poly (ADP-ribose); PARG: PAR glycohydrolase; PARP: poly (ADP-ribose) polymerase; Pt: platinum; SCLC: small cell lung cancer; TTFields: tumor treating fields. 1. Adapted from O’Shaughnessy J et al. 2009 American Society of Clinical Oncology Annual Meeting (ASCO 2009). Abstract 3. 2. Adapted from Toss A, Cortesi L. J Cancer Sci Ther. 2013;5:409-416. 3. Lynparza (olaparib) Prescribing Information. https://www.azpicentral.com/lynparza_tb/lynparza_tb.pdf#page=1. 4. Aschenbrenner DS. Am J Nurs. 2020;120:22-23. 5. Gutin PH, Wong ET. Am Soc Clin Oncol Educ Book. 2012;32:126-131. 6. Kirson ED et al. Proc Natl Acad Sci USA. 2007;104:10152-10157. 7. Gutin PH, Wong ET. Am Soc Clin Oncol Educ Book. 2012;32:126-131. 8. Kirson ED et al. Proc Natl Acad Sci USA. 2007;104:10152-10157. Access the activity, “Making Headway Toward Better Outcomes in Pancreatic Cancer: The Oncology Nurse as a Leader and Advocate for Patients in an Era of Advances in Care and Research,” at PeerView.com/USV40 PRACTICE AID

Management of Common Adverse Events Pancreatic Cancer Associated With Chemotherapy Platforms www.letswinpc.org

FOLFIRINOX1

Neutropenia/Febrile Neutropenia/Thrombocytopenia

• Decrease dose of 5-FU or oxaliplatin; omit irinotecan for febrile neutropenia • Delay treatment until neutrophils ≥1.5 × 109/L after grade 4 neutropenia2

Diarrhea

• Decrease dose of ≥1 component • Diarrhea occurring >24 h after injection may be prolonged and life threatening3 −− Treat promptly with loperamide, fluids, and electrolytes

Infusion Reactions

• Slow infusion time, provide atropine and/or proton pump • Desensitization protocols

Management of Common Adverse Events Pancreatic Cancer Associated With Chemotherapy Platforms www.letswinpc.org

Nab-Paclitaxel + Gemcitabine4-5

Neutropenia/Febrile Neutropenia/Thrombocytopenia

• Dose reduction or delays at days 8 and/or 15 based upon severity of neutropenia and prior dose reductions

Gastrointestinal Toxicity

• For grade 3 or 4: withhold until grade ≤1 • Resume at next lower dose level

Cutaneous Toxicity • For grade 2 or 3: reduce to next lower level • Discontinue if toxicity persists

Peripheral Neuropathy • Withhold therapy for grade 3 or 4 peripheral neuropathy • Resume therapy at next lower dose level when neuropathy improves to ≤ grade 1

Management of Common Adverse Events Pancreatic Cancer Associated With Chemotherapy Platforms www.letswinpc.org

Nal-Irinotecan (Nal-IRI): Dose Modification6 Patients homozygous for Nal-IRI adjustment in patients Toxicity NCI CTCAE v4.0a Directions UGT1A1*28 (who are currently receiving 70mg/m2 receiving 50 mg/m2) • Withhold Nal-IRI. • Administer loperamide for late diarrhea of any severity. Grade 2 Diarrhea N/A N/A • Administer atropine, if not contraindicated, for early diarrhea of any severity. • Withhold Nal-IRI. First Occurrence • Administer loperamide for late 50 mg/m2 43 mg/m2 diarrhea of any severity. • Administer intravenous or Second Occurrence Grade 3 or 4 Diarrhea subcutaneous atropine 0.25 mg to 1 mg (unless contraindicated) for 43 mg/m2 35 mg/m2 early diarrhea of any severity. Third Occurrence • Upon recovery to ≤grade 1, resume Nal-IRI at a modified dose. Discontinue Nal-IRI First Occurrence 50 mg/m2 43 mg/m2 • Withhold Nal-IRI. Upon recovery Second Occurrence Grade 3 or 4 Adverse Reactions to ≤grade 1, resume Nal-IRI at a 2 2 modified dose. 43 mg/m 35 mg/m Third Occurrence Discontinue Nal-IRI Interstitial Lung Disease or First Occurrence: Discontinue Nal-IRI Anaphylactic Reaction a National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 used for grading. 1. Marsh RDW et al. Cancer Med. 2015;4:853-863. 2. Eloxatin (oxaliplatin) Prescribing Information. http://products.sanofi.us/eloxatin/eloxatin.html. 3. Camptosar (irinotecan) Prescribing Information. http://www.pfizer.com/products/product-detail/camptosar. 4. Scheithauer W et al. J Gastrointest Oncol. 2016;7:469-478. 5. Abraxane (paclitaxel) Prescribing Information. (https://packageinserts.bms.com/pi/pi_abraxane.pdf. 6. Onivyde (irinotecan liposome) Prescribing Information. https://www.onivyde.com/websites/onivyde_us_online/wp-content/uploads/sites/2/2018/12/12185529/ ONV-US-000907-Onivyde-Dosing-Guide.pdf. Access the activity, “Making Headway Toward Better Outcomes in Pancreatic Cancer: The Oncology Nurse as a Leader and Advocate for Patients in an Era of Advances in Care and Research,” at PeerView.com/USV40