A Study to Assess the Efficacy and Safety of IMAB362 in Combination With Nab-Paclitaxel and Gemcitabine (Nab-P + GEM) as First Line Treatment in Subjects With Claudin 18.2 (CLDN18.2) Positive, Metastatic Pancreatic Adenocarcinoma

Pancreatic Cancer Clinical Trial

Official title:

A Phase 2, Open-Label, Randomized Study to Assess the Efficacy and Safety of Zolbetuximab (IMAB362) in Combination With Nab-Paclitaxel and Gemcitabine (Nab-P + GEM) as First Line Treatment in Subjects With Claudin 18.2 (CLDN18.2) Positive, Metastatic Pancreatic Adenocarcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03816163
• Other study ID #: 8951-CL-5201
• Secondary ID: 2018-002551-15CT
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 15, 2019
• Est. completion date: April 30, 2025

Study information

• Verified date: May 2024
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to confirm the recommended phase 2 dose (RP2D) of zolbetuximab in combination with Nab-P + GEM, determine overall survival and assess the safety and tolerability of the combination treatment. This study will also evaluate tumor markers and pharmacokinetics (PK) of zolbetuximab, Nab-P and GEM, and health-related quality of life (HRQoL).

Description:

This study will have a safety lead in phase and a randomization phase.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 393
• Est. completion date: April 30, 2025
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• A female subject is eligible to participate if she is not pregnant or lactating and at

least 1 of the following conditions applies:

• Not a woman of childbearing potential (WOCBP) OR
• WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 6 months after the final study drug administration.
• Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration.
• Female subject must not donate ova starting at screening and throughout the study period, and for 6 months after the final study drug administration.
• A male subject with female partner(s) of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration.
• A male subject must not donate sperm during the treatment period and for at least 6 months after the final study drug administration.
• Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration.
• Subject agrees not to participate in other interventional studies while receiving study drug in present study.
• Subject has histologically or cytologically confirmed adenocarcinoma of pancreas.
• Subjects must have metastatic pancreatic adenocarcinoma that has not been previously treated with chemotherapy.
• Prior treatment with fluorouracil (5-FU) or GEM administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed
• If a subject received adjuvant therapy, tumor recurrence or disease progression must have occurred at least 6 months after completing the last dose of the adjuvant therapy.
• Subjects whose disease progressed on prior treatment with Nab-P and GEM are not eligible.
• Subject has a measurable lesion(s) on at least 1 metastatic site based on RECIST 1.1 within 28 days prior to randomization. For subjects with only 1 measurable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
• Subject's tumor sample has CLDN18.2 expression in = 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing
• Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Subject has predicted life expectancy = 12 weeks.
• Subject must meet all of the following criteria based on the laboratory tests that will be collected within 14 days prior to randomization. In case of multiple laboratory data within this period, the most recent data should be used.
• Hemoglobin = 9 g/dl (no transfusion within 14 days of start of study treatment)
• Absolute neutrophil count = 1.5 x 10^9/L
• Platelets = 100 x 10^9/L
• Albumin = 2.5 g/dL
• Total bilirubin = 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x ULN without liver metastases (= 5 x ULN if liver metastases are present)
• Estimated creatinine clearance = 30 mL/min
• Prothrombin time/international normalized ratio (INR) and partial thromboplastin time = 1.5 x ULN (except for subjects receiving anticoagulation therapy)

Exclusion Criteria:

• Subject has received other investigational treatment within 28 days prior to randomization.
• Subject has received radiotherapy for metastatic pancreatic adenocarcinoma = 14 days prior to randomization and has not recovered from any related toxicity.
• Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to randomization. Subject using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone), receiving a single dose of systemic corticosteroids or receiving systemic corticosteroids as premedication for radiologic imaging contrast use are allowed.
• Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibody, including humanized or chimeric antibodies.
• Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
• Subject has a known history of a positive test for human immunodeficiency virus infection or known active hepatitis B (positive HBs antigen [Ag]) or hepatitis C infection. NOTE: Screening for these infections should be conducted per local requirements.

1. For subjects who are negative for HBs Ag, but hepatitis B core antibody positive, a hepatitis B virus DNA test will be performed and if positive, the subject will be excluded.

2. Subjects with positive hepatitis C serology but negative hepatitis C virus RNA test results are eligible.

3. Subjects treated for hepatitis C with undetectable viral load results are eligible.

• Subject has a history of interstitial pneumonia or pulmonary fibrosis.
• Subject has pleural effusion or ascites = Grade 3.
• Subject has an active autoimmune disease that has required systemic treatment in the past 3 months prior to randomization.
• Subject has active infection requiring systemic therapy that has not completely resolved per investigator judgment within 7 days prior to randomization.
• Subject has significant cardiovascular disease, including:
• Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to randomization;
• History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
• QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects;
• Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for > 1 month prior to randomization.)
• Subject has a history of central nervous system metastases and/or carcinomatous meningitis from pancreatic adenocarcinoma.
• Subject has known peripheral sensory neuropathy = Grade 2 unless the absence of deep tendon reflexes is the sole neurological abnormality.
• Subject has had a major surgical procedure = 28 days prior to randomization.
• Subject without complete recovery from a major surgical procedure = 14 days prior to randomization.
• Psychiatric illness or social situations that would preclude study compliance.
• Subject has another malignancy for which treatment is required.
• Subject has any concurrent disease, infection or co-morbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data.

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Pancreatic Adenocarcinoma
• Metastatic Pancreatic Cancer
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• zolbetuximab
Administered as an intravenous infusion.
• nab-paclitaxel
Administered as an intravenous infusion
• gemcitabine
Administered as an intravenous infusion

Locations

Country	Name	City	State
Australia	Site AU61005	Fitzroy	Victoria
Australia	Site AU61008	Gosford	New South Wales
Australia	Site AU61006	Warrnambool	Victoria
Australia	Site AU61007	Wollongong	New South Wales
Brazil	Site BR55009	Centro Passo Fundo
Brazil	Site BR55012	Porto Alegre	Rio Grande Do Sul
Brazil	Site BR55008	Rio Grande Do Sul
Brazil	Site BR55004	Santa Catarina
Brazil	Site BR55010	Sao Paulo
Brazil	Site BR55011	Sao Paulo
China	Site CN86001	Beijing
China	Site CN86008	Beijing
China	Site CN86014	Beijing
China	Site CN86026	Changchun
China	Site CN86009	Chongqing
China	Site CN86004	Guangdong
China	Site CN86020	Guangdong
China	Site CN86016	Guangzhou
China	Site CN86012	Harbin
China	Site CN86002	Hubei
China	Site CN86005	Jiangsu
China	Site CN86011	Jiangsu
China	Site CN86025	Jiangsu
China	Site CN86024	Shan XI
China	Site CN86023	Shandong
China	Site CN86006	Shanghai
China	Site CN86013	Shanghai
China	Site CN86019	Shanghai
China	Site CN86007	Tianjin
China	Site CN86022	Xinjiang
China	Site CN86003	Zhejiang
China	Site CN86018	Zhejiang
China	Site CN86010	Zhengzhou
France	Site FR33003	Aquitaine	Pessac
France	Site FR33001	Bayonne Cedex
France	Site FR33008	Besancon	Besancon Cedex
France	Site FR33018	Bordeaux
France	Site FR33010	Brest	Brest Cedex
France	Site FR33015	Caen	Cedex 5
France	Site FR33006	Chambray	Cedex 9
France	Site FR33002	Grenoble
France	Site FR33012	Herblain	Herblain Cedex
France	Site FR33016	La Chaussee Saint Victor	Loir-et-Cher
France	Site FR33009	Nancy	Nancy Cedex
France	Site FR33021	Nice Cedex 2
France	Site FR33023	Pierre Benite
France	Site FR33014	Plerin
France	Site FR33005	Pringy Cedex
France	Site FR33019	Roche-Sur-Yon
France	Site FR33017	Rouen	Normandy
France	Site FR33007	Strasbourg
France	Site FR33013	Villejuif	Villejuif Cedex
Ireland	Site IR35301	Elm Park	Dublin
Italy	Site IT39004	Candiolo	Torino
Italy	Site IT39002	Cremona
Italy	Site IT39010	Lombardia
Italy	Site IT39003	Milan
Italy	Site IT39006	Rozzano	Milan
Italy	Site IT39014	Toscana
Italy	Site IT39008	Veneto
Japan	Site JP81011	Bunkyo-ku	Tokyo
Japan	Site JP81012	Chuo-ku	Tokyo
Japan	Site JP81004	Fukuoka
Japan	Site JP81003	Kashihara	Nara
Japan	Site JP81001	Kashiwa	Chiba
Japan	Site JP81014	Koto-ku	Tokyo
Japan	Site JP81013	Mitaka	Tokyo
Japan	Site JP81007	Nagoya	Aichi
Japan	Site JP81010	Osaka
Japan	Site JP81005	Sapporo	Hokkaido
Japan	Site JP81002	Shinjuku-ku	Tokyo
Japan	Site JP81015	Ube	Yamaguchi
Japan	Site JP81009	Wakayama
Japan	Site JP81006	Yokohama	Kanagawa
Korea, Republic of	Site KR82010	Daegu
Korea, Republic of	Site KR82009	Gyeonggi-do
Korea, Republic of	Site KR82011	Jeollanam-do
Korea, Republic of	Site KR82005	Seongnam-Si	Gyeonggi-do
Korea, Republic of	Site KR82001	Seoul
Korea, Republic of	Site KR82002	Seoul
Korea, Republic of	Site KR82003	Seoul
Korea, Republic of	Site KR82004	Seoul
Korea, Republic of	Site KR82006	Seoul
Korea, Republic of	Site KR82007	Seoul
Korea, Republic of	Site KR82008	Suwon-si	Gyeonggi-do
Mexico	Site MX52004	Distrito Federal
Mexico	Site MX52003	San Luis Potosi
Mexico	Site MX52005	Veracruz
Spain	Site ES34007	Barcelona
Spain	Site ES34010	Barcelona
Spain	Site ES34013	Barcelona
Spain	Site ES34018	Barcelona
Spain	Site ES34021	Barcelona
Spain	Site ES34014	Caceres
Spain	Site ES34022	Cordoba
Spain	Site ES34005	Lleida
Spain	Site ES34004	Llobregat	Barcelona
Spain	Site ES34006	Madrid
Spain	Site ES34009	Madrid
Spain	Site ES34015	Madrid
Spain	Site ES34026	Malaga
Spain	Site ES34003	Pamplona	Navarra
Spain	Site ES34024	Santander
Spain	Site ES34017	Santiago de Compostela
Taiwan	Site TW88608	New Taipei City
Taiwan	Site TW88602	Taichung City
Taiwan	Site TW88601	Taipei City
Taiwan	Site TW88609	Taipei City
Turkey	Site TR90004	Ankara
Turkey	Site TR90006	Ankara
Turkey	Site TR90003	Diyarbakir
Turkey	Site TR90002	Istanbul
Turkey	Site TR90001	Konya
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Lynn Cancer Institute	Boca Raton	Florida
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	David C Pratt Cancer Center	Creve Coeur	Missouri
United States	St. Joseph Heritage Medical Group	Fullerton	California
United States	MultiCare Regional Cancer Center - Gig Harbor	Gig Harbor	Washington
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Houston Methodist Hospital	Houston	Texas
United States	Northwell Health Cancer Institute	Lake Success	New York
United States	Norton Cancer Institute (NCI)	Louisville	Kentucky
United States	Midstate Medical Center	Meriden	Connecticut
United States	Baptist Health	Miami	Florida
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Ochsner Health System	New Orleans	Louisiana
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Cancer Treatment Centers of Atlanta	Newnan	Georgia
United States	Vista Oncology	Olympia	Washington
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Virginia Mason	Seattle	Washington
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	TOI Clinical research	Whittier	California
United States	Novant Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  China,  France,  Ireland,  Italy,  Japan,  Korea, Republic of,  Mexico,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicities (DLT) - (safety lead in)	Incidence of dose limiting toxicities.	Up to 28 days
Primary	Overall Survival (OS)	OS is defined as the time from the date of randomization until the date of death from any cause.	Up to 65 months
Primary	Safety assessed by Adverse Events (AEs)	An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.	Up to 65 months
Primary	Safety assessed by incidence of serious adverse events (SAE)	Adverse Event (AE) is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important event.	Up to 65 months
Primary	Safety assessed by incidence of treatment emergent adverse events (TEAE)	Treatment Emergent Adverse Event (TEAE) is defined as any AE which starts, or worsens, after the first dose of study drug through 30 days after the last dose of study drug.	Up to 65 months
Primary	Number of participants with laboratory value abnormalities and/or adverse events (AEs)	Number of participants with potentially clinically significant laboratory values.	Up to 65 months
Primary	Number of participants with vital sign abnormalities and /or adverse events (AEs)	Number of participants with potentially clinically significant vital sign values.	Up to 65 months
Primary	Number of participants with electrocardiograms (ECG) abnormalities and or adverse events	12-lead ECGs will be recorded. Prior to the ECG, participants should rest in supine position for 10 minutes. ECGs will be read and assessed locally.	Up to 65 months
Primary	Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities and or adverse events	Number of participants with potentially clinically significant ECOG performance status values. ECOG grades 0-5, where 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair and 5 = Dead.	Up to 65 months
Secondary	Progression Free Survival (PFS)	PFS is defined as the time from the date of randomization until the date of radiological progressive disease (PD) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 by investigator evaluation or death from any cause, whichever is earliest.	Up to 65 months
Secondary	Objective Response Rate (ORR)	ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by investigator evaluation per RECIST 1.1.	Up to 65 months
Secondary	Number of anti-drug antibody (ADA) Positive Participants	Immunogenicity will be measured by the number of participants that are ADA positive.	Up to 65 months
Secondary	Disease Control Rate (DCR)	DCR is defined as the proportion of participants who have best overall response of stable disease, complete response (CR) or partial response (PR) as assessed by investigator evaluation per RECIST 1.1	Up to 65 months
Secondary	Duration Of Response (DOR)	DOR is defined as the time from the date of the first response (CR/PR) until the date of progressive disease as assessed by investigator evaluation per RECIST 1.1 or date of death from any cause, whichever is earliest.	Up to 65 months
Secondary	Change in CA (Cancer Antigen) 19-9	Change from baseline in serum CA19-9 will be assessed.	Baseline up to 65 months
Secondary	PK of zolbetuximab: Concentration Immediately Prior to Dosing (Ctrough)	Ctrough will be derived from the PK serum samples collected.	Up to 65 months
Secondary	PK of Nab-P: Area Under the Concentration-time Curve from the Time of Dosing Extrapolated to Time Infinity (AUCinf)	AUCinf will be derived from the PK plasma samples collected.	Up to 30 days
Secondary	PK of Nab-P: Area Under the Concentration-time Curve from the Time of Dosing Until the Last Measurable Concentration (AUClast)	AUClast will be derived from the PK plasma samples collected.	Up to 30 days
Secondary	PK of Nab-P: Maximum Concentration (Cmax)	Cmax will be derived from the PK plasma samples collected.	Up to 30 days
Secondary	PK of Nab-P: Time of Maximum Concentration (Tmax)	Tmax will be derived from the PK plasma samples collected.	Up to 30 days
Secondary	PK of Nab-P: Terminal Elimination Half-life (T1/2)	T1/2 will be derived from the PK plasma samples collected.	Up to 30 days
Secondary	PK of Nab-P: Clearance (CL)	CL will be derived from the PK plasma samples collected.	Up to 30 days
Secondary	PK of Nab-P: Volume of Distribution During the Terminal Phase (Vz)	Vz will be derived from the PK plasma samples collected.	Up to 30 days
Secondary	PK of gemcitabine: Area Under the Concentration-time Curve from the Time of Dosing Extrapolated to Time Infinity (AUCinf)	AUCinf will be derived from the PK plasma samples collected.	Up to 30 days
Secondary	PK of gemcitabine: Area Under the Concentration-time Curve from the Time of Dosing Until the Last Measurable Concentration (AUClast)	AUClast will be derived from the PK plasma samples collected.	Up to 30 days
Secondary	PK of gemcitabine: Maximum Concentration (Cmax)	Cmax will be derived from the PK plasma samples collected.	Up to 30 days
Secondary	PK of gemcitabine: Time of Maximum Concentration (Tmax)	Tmax will be derived from the PK plasma samples collected.	Up to 30 days
Secondary	PK of gemcitabine: Terminal Elimination Half-life (T1/2)	T1/2 will be derived from the PK plasma samples collected.	Up to 30 days
Secondary	PK of gemcitabine: Clearance (CL)	CL will be derived from the PK plasma samples collected.	Up to 30 days
Secondary	PK of gemcitabine: Volume of Distribution During the Terminal Phase (Vz)	Vz will be derived from the PK plasma samples collected.	Up to 30 days
Secondary	Health Related Quality of Life (HRQoL) measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire (EORTC-QLQ-C30)	The EORTC-QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." For functional scales, higher scores indicate better functioning, while for symptom scales/items, higher scores indicate worse symptoms.	Up to 65 months
Secondary	Health Related Quality of Life (HRQoL) measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Pancreatic Cancer Module (EORTC-QLQ-PAN-26)	EORTC-QLQ-PAN26 is a 26-item questionnaire that evaluates pancreatic cancer-specific symptoms such as pain, dietary changes, jaundice, altered bowel habits, and emotional problems. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." For symptom scales/items, higher scores indicate worse symptoms.	Up to 65 months
Secondary	Health Related Quality of Life (HRQoL) measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L)	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome consisting of 6 items that cover 5 main domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a general visual analog scale for health status.; Each domain comprises 5 severity levels (no problems, slight problems, moderate problems, severe problems, extreme problems). The general visual analog scale records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale. Responses to the 5 items will also be converted to a weighted health state index (utility score) based on values derived from general population samples.	Up to 65 months
Secondary	Health Related Quality of Life (HRQoL) measured by the Patient Global Impression of Change (PGIC) scale	The PGIC is a single-item questionnaire that asks participants to provide the overall self-assessment of change in their disease on a 7-point scale ranging from "very much worse" to "very much better" as compared to the participant starting the study treatment. Only PGIC questions assessing pain and overall status will be collected.	Up to 65 months
Secondary	Health Related Quality of Life (HRQoL) measured by the Patient Global Impression of Severity (PGIS) Scale	The PGIS is a single-item questionnaire that asks participants to provide the overall self-assessment of their disease severity on a 4-point scale for the past week, with 1 as "None" and 4 as "Severe". Only PGIS questions assessing pain and overall status will be collected.	Up to 65 months
Secondary	Time to Improvement of pancreatic pain as measured by Quality-of-Life Questionnaire - Core Questionnaire (QLQ-C30)	The QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." For functional scales, higher scores indicate better functioning, while for symptom scales/items, higher scores indicate worse symptoms.	Up to 65 months
Secondary	Time to worsening of global health status (GHS)/quality of life (QoL) as measured by QLQ-C30	The QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." For functional scales, higher scores indicate better functioning, while for symptom scales/items, higher scores indicate worse symptoms.	Up to 65 months
Secondary	Time to Improvement of pancreatic pain as measured by Quality of Life Questionnaire - Pancreatic Cancer Module 26 (QLQ-PAN26)	EORTC-QLQ-PAN26 is a 26-item questionnaire that evaluates pancreatic cancer-specific symptoms such as pain, dietary changes, jaundice, altered bowel habits, and emotional problems. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." For symptom scales/items, higher scores indicate worse symptoms.	Up to 65 months
Secondary	Time to worsening of GHS/QoL as measured by QLQ-PAN26	EORTC-QLQ-PAN26 is a 26-item questionnaire that evaluates pancreatic cancer-specific symptoms such as pain, dietary changes, jaundice, altered bowel habits, and emotional problems. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." For symptom scales/items, higher scores indicate worse symptoms.	Up to 65 months
Secondary	Time to Improvement of pancreatic pain as measured by PGIS	The PGIS is a single-item questionnaire that asks participants to provide the overall self-assessment of their disease severity on a 4-point scale for the past week, with 1 as "None" and 4 as "Severe". Only PGIS questions assessing pain and overall status will be collected.	Up to 65 months
Secondary	Time to worsening of GHS/QoL as measured by PGIS	The PGIS is a single-item questionnaire that asks participants to provide the overall self-assessment of their disease severity on a 4-point scale for the past week, with 1 as "None" and 4 as "Severe". Only PGIS questions assessing pain and overall status will be collected.	Up to 65 months