A Multi-center Trial to Evaluate Multiple Regimens in Metastatic Pancreatic Cancer

NCT04229004 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: PanCAN_Precision Promise
• Study Type: interventional
• Target: 502
• Locations: 1 country
• Sites: 25

Brief Summary

Precision Promise is a multi-center, seamless Phase 2/3 platform trial designed to evaluate multiple regimens in metastatic pancreatic cancer. Primary Objectives

• To compare each investigational arm versus standard of care (SOC) for superiority in overall survival in first and/or second line metastatic ductal adenocarcinoma (metastatic pancreatic cancer) participants and determine which, if any, participants benefit from each investigational arm. Secondary Objectives
• To determine short and long-term safety signals of each investigational arm in metastatic pancreatic cancer participants vs. SOC.
• To determine progression-free survival (PFS) for each investigational arm vs. SOC.
• To determine rates of overall response, CR, and PR; duration of overall response, CR or PR (whichever occurs first).
• To determine rates of clinical benefit; duration of clinical benefit.

Conditions

Metastatic Pancreatic Cancer; Metastatic Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival (OS) is defined from the time of initiation of treatment until death due to any cause. Participants still alive at the time of an analysis will be considered censored at their date of last contact.

  0 weeks

Secondary Outcomes (5)

• Progression free survival (PFS)

  From initiation of therapy to clinically determined disease progression or death due to any cause, whichever came first, assessed up to 24 months.

• Performance Status

  From screening through study completion, an average of 2 years.

• Overall Response Rate (ORR)

  From initiation of treatment to clinically determined tumor size reduction for a minimum of 4 weeks

• Duration of Overall Response Rate (ORR)

  From date of first occurrence of a documented objective response to date of clinically determined disease progression or death due to any cause, whichever came first, assessed up to 24 months.

• Duration of Clinical Benefit

  From screening through last dose of therapy, assessed up to 24 months.

Study Arms (5)

Gemcitabine combined with nab-paclitaxel

ACTIVE COMPARATOR

Arm is closed to recruitment. The following are recommended parameters for infusion timing and sequence, although institutional variation in the administration of the regimen are permitted as long as drug dosing and modification guidelines are followed.

Drug: Gemcitabine combined with nab-paclitaxel

mFOLFIRINOX

ACTIVE COMPARATOR

Arm is closed to recruitment. Oxaliplatin 85 mg/m2, Leucovorin 400 mg/m2, Irinotecan 150 mg/m2, 5-Fluorouracil 2400 mg/m2 46-48 hour infusion

Drug: Dose -mFOLFIRINOX

pamrevlumab (FibroGen)

EXPERIMENTAL

Arm is closed to recruitment. Experimental: Pamrevlumab in combination with gemcitabine/nab-paclitaxel. Participants enrolled to this treatment arm will receive treatment with pamrevlumab in combination with gemcitabine and nab-paclitaxel. Gemcitabine and nab-paclitaxel are FDA approved therapies for metastatic pancreatic cancer and will be supplied or obtained according to local clinical study agreements and in accordance with local guidelines.

Drug: Dose - Pamrevlumab combined with gemcitabine and nab-paclitaxel

Canakinumab and Spartalizumab

EXPERIMENTAL

Arm is closed to recruitment. Canakinumab and Spartalizumab in Combination with Nab-Paclitaxel and Gemcitabine. Participants enrolled to this treatment arm will receive treatment with Canakinumab and Spartalizumab in combination with nab-paclitaxel and gemcitabine.

Drug: Dose- Canakinumab and Spartalizumab combined with nab-paclitaxel and gemcitabine

Experimental: SM-88

EXPERIMENTAL

Arm is closed to recruitment. 460 mg (2 capsules) twice daily of a 28-day cycle along with the administration of methoxsalen, phenytoin and sirolimus. All four agents (SM-88, methoxsalen, phenytoin, and sirolimus) should be dosed with approximately 240 mL (8 fl. oz.) of water in the morning. All four agents should be taken together consistently. SM-88 used with MPS should ideally be taken approximately 1 hour before or 2 hours after a meal.

Drug: Drug: Dose -SM-88

Interventions

Gemcitabine combined with nab-paclitaxel DRUG

Arm is closed to recruitment. Nab-paclitaxel is infused over 30-40 min on days 1, 8, 15 of each 28-day cycle. Gemcitabine is infused over 30 min, immediately after completion of nab-paclitaxel infusion, on days 1, 8, 15 of each 28-day cycle. If one of the chemotherapy medications is held, the other study medications may be given. Doses should be re-adjusted if the participant's weight changes by +/- \>10%. If the participant's weight changes by \<10%, no adjustment is necessary unless the site has a standard procedure to adjust doses based upon current weight according to institutional guidelines.

Gemcitabine combined with nab-paclitaxel

Dose -mFOLFIRINOX DRUG

Arm is closed to recruitment. The following are recommended parameters for infusion timing and sequence, although institutional variation in the administration of the regimen are permitted, as long as drug dosing and modification guidelines are followed. Oxaliplatin and leucovorin are administered concurrently over 30-120 minutes, followed by irinotecan over 30-90 minutes, followed by the infusion of 5-flurouracil. If one of the chemotherapy medications is held, the other study medications may be given. Doses should be re-adjusted if the participant's weight changes by +/- \>10%. If the participant's weight changes by \<10%, no adjustment is necessary unless the site has a standard procedure to adjust doses based upon current weight according to institutional guidelines.

mFOLFIRINOX

Dose - Pamrevlumab combined with gemcitabine and nab-paclitaxel DRUG

Arm is closed to recruitment. Pamrevlumab 35mg/kg IV - Cycle 1 (Day 1, 8, 15 of the 28 day cycle) and Cycle 2 and Onward (Day 1 and 15) Nab-paclitaxel 125mg/m2 IV - Day 1, 8, 15 for every 28 day cycle Gemcitabine 1000mg/m2 IV - Day 1, 8, 15 for every 28 day cycle

pamrevlumab (FibroGen)

Dose- Canakinumab and Spartalizumab combined with nab-paclitaxel and gemcitabine DRUG

Arm is closed to recruitment. Canakinumab 250mg SC- Day 1 of every 28 day cycle Spartalizumab 400 mg IV - Day 1 of every 28 day cycle Nab-paclitaxel 125mg/m2 IV - Day 1, 8, 15 of every 28 day cycle Gemcitabine 1000mg/m2 IV - Day 1, 8, 15 of every 28 day cycle

Canakinumab and Spartalizumab

Drug: Dose -SM-88 DRUG

Arm is closed to recruitment. 460 mg (2 capsules) twice daily of a 28-day cycle along with the administration of methoxsalen, phenytoin and sirolimus.

Experimental: SM-88

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC) and eligible for treatment in the first line or second line settings.
• Acceptable histologies include adenosquamous carcinoma, mucinous adenocarcinoma, hepatoid carcinoma, medullary carcinoma, signet ring cell carcinoma, undifferentiated carcinoma, and undifferentiated carcinoma with osteoclast-like-cells, and adenocarcinoma. Pancreatic neuroendocrine tumors (PNET) are excluded.
• Radiographically measurable disease by computed tomography (CT) scan or magnetic resonance imaging (MRI) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Imaging results must be obtained within the 28-day window, prior to randomization.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Adequate organ function (lab results must be obtained within the 28-day window prior to randomization)
• Absolute neutrophil count ≥ 1500/mm3
• Hemoglobin ≥ the lower limit of normal (LLN) or 9g/dL
• Platelets ≥ 100,000/mm3
• Serum creatinine ≤ 1.0 x upper limit normal (ULN), or calculated creatinine clearance ≥ 50 mL/min (Cockcroft Gault)
• Albumin ≥ 3.0 g/dL
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 x ULN (up to ≤ 5 x ULN in presence of liver metastasis).
• Total bilirubin ≤ 1.5 x ULN
• INR ≤ 1.5 x ULN (up to ≤ 2 x ULN for participants on anticoagulation therapy).
• Participants must be willing to provide protocol-mandated tissue and blood samples for diagnostic and research purposes as a condition of enrollment into the trial.

You may not qualify if:

• A participant will not be eligible to participate in Precision Promise if any of the following criteria are met:
• Received any anti-cancer systemic therapy within 21 days (or 5 half-lives, whichever is shorter,) prior to randomization.
• Has had major surgery within 14 days prior to enrollment.
• History of known allergy or hypersensitivity to any of the study treatments or any of their excipients or contraindication to any of the study treatments as outlined in the local prescribing information (e.g., United States Prescribing Information \[USPI\]).
• Pre-existing peripheral neuropathy \> Grade 1, as defined by CTCAE V 4.03.
• Known active tuberculosis infection.
• Serious, non-healing wound, ulcer, or bone fracture.
• The inability to swallow pills, capsules or tablets.
• Receiving any active therapy for concurrent secondary malignancy. Participants with a prior or concurrent malignancy whose natural history and/or management does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible.
• History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, and pulmonary hypersensitivity pneumonitis.
• QTc \> 450 msec if male and QTc \> 470 msec if female.
• Uncontrolled or severe cardiac disease (history of unstable angina, myocardial infarction, coronary stenting, or bypass surgery within the prior 6 months), symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia \[including atrial flutter/fibrillation\].
• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using New York Heart Association Functional Classification. Participants worse than Class 2 are excluded. Class 2 is defined as slight limitation of physical activity, in which ordinary physical activity leads to fatigue, palpitation, or dyspnea; the person is comfortable at rest.
• Active, uncontrolled infections (bacterial, viral, or fungal infection(s)) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment (i.e., Participants must be afebrile for \> 48 hours off antibiotics).
• Active, known or suspected autoimmune disease, including systemic lupus erythematosus, Hashimotos thyroiditis, scleroderma, polyarteritis nodosa or autoimmune hepatitis.

Sponsors & Collaborators

• Pancreatic Cancer Action Network: lead

Study Sites (25)

University of California, San Diego (UCSD) - Moores Cancer Center

La Jolla, California, 92037, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048-1804, United States

Location

University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136-1002, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan - Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic Cancer Center (MCCC)

Rochester, Minnesota, 55905-0001, United States

Location

Siteman Cancer Center - Washington University Medical Campus

St Louis, Missouri, 63110-1010, United States

Location

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87102, United States

Location

New York University Langone Medical Center - Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Evelyn H. Lauder Breast Center - Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Physicians - Solid Tumor/Gastrointestinal Oncology

New York, New York, 10065, United States

Location

University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45267, United States

Location

University of Pennsylvania - Abramson Cancer Center

Philadelphia, Pennsylvania, 19104-5127, United States

Location

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030-3411, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Virginia Commonwealth University School of Medicine

Richmond, Virginia, 23219, United States

Location

Virginia Mason Hospital & Seattle Medical Center

Seattle, Washington, 98101, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226-3522, United States

Location

Related Publications (1)

• Rayego-Mateos S, Morgado-Pascual JL, Lavoz C, Rodrigues-Diez RR, Marquez-Exposito L, Tejera-Munoz A, Tejedor-Santamaria L, Rubio-Soto I, Marchant V, Ruiz-Ortega M. CCN2 Binds to Tubular Epithelial Cells in the Kidney. Biomolecules. 2022 Feb 3;12(2):252. doi: 10.3390/biom12020252.

  PMID: 35204752 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2019
• First Posted: January 14, 2020
• Study Start: January 31, 2020
• Primary Completion: February 5, 2025
• Study Completion: February 5, 2025
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (25)