Clinical trial NCT04229004: A Multi-center Trial to Evaluate Multiple Regimens in Metastatic Pancreatic Cancer
Official title: Precision Promise Platform Trial for Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Pancreatic Cancer
Metastatic Pancreatic Adenocarcinoma
Lead sponsor: Pancreatic Cancer Action Network
Sponsor class: OTHER
First posted: 2020-01-14
Enrollment: 502
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Precision Promise is a multi-center, seamless Phase 2/3 platform trial designed to evaluate multiple regimens in metastatic pancreatic cancer. The goal of the platform is to find effective therapies for pancreatic cancer. The platform will test multiple investigational drugs and combinations compared to standard of care therapy in first and second line metastatic participants. Bayesian response-adaptive randomization will be used to assign participants to arms based on their performance in subtypes of the disease. The primary endpoint is overall survival.

Eligibility criteria: Inclusion Criteria

A participant will be eligible to participate in Precision Promise if all the below inclusion criteria are met:

* 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.
* Able to swallow pills, capsules or tablets.
* Able to adhere to study visit schedule and other protocol requirements.
* Participants of childbearing potential \[defined as a person assigned as female at birth who (1) have not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months)\] must:

  * Have a negative serum or urine pregnancy test (β-human chorionic gonadotropin \[β-hCG\]) as verified by the study doctor within 14 days prior to randomization.
  * Commit to complete abstinence from sexual contact with persons assigned as male at birth or agree to use medical doctor-approved contraception without interruption while participating in the study, during dose interruptions and for at least 6 months following last dose of study treatment.
* Participants assigned as males at birth must practice complete abstinence or agree to use a condom (even if he has undergone a successful vasectomy) during sexual contact with persons of childbearing potential while participating in the study, during dose interruptions and for at least 6 months following last dose of study treatment.
* known HIV-infected participants on effective anti-retroviral therapy are eligible if the most recent viral load test performed within six months of screening (based on medical chart review) is negative. If this is not the case, an HIV viral load test should be performed at screening and be negative (i.e., undetectable).
* Known HBV-infected participants are eligible if the most recent viral load test performed within six months of screening (based on medical chart review) is negative. If this is not the case, an HBV viral load test should be performed at screening and be negative (i.e., undetectable).
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with known HCV infection who are currently on treatment are eligible if the most recent viral load test performed within six months of screening (based on medical chart review) is negative. If this is not the case, an HCV viral load test should be performed at screening and be negative (i.e., undetectable).
* Participants with a history of brain metastases are eligible provided they show evidence of stable lesions (and no new lesions) with no evidence of tumor progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. In addition, any neurological symptoms that developed either as a result of the brain metastases or their treatment, must have returned to baseline or resolved. Any steroids administered as part of this therapy must be completed \> 7 days prior to the first dose of trial therapy.
* No known leptomeningeal disease.
* Participants with a prior or concurrent malignancy whose natural history does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible. Participants receiving any active therapy for a concurrent secondary malignancy are excluded.
* 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. To be eligible for this trial, participants should be Class 2 or better. 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.
* Understands the nature of the study and has agreed to participate by voluntarily signing the IRB approved informed consent.

Exclusion Criteria

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.

  o Participants with type I diabetes mellitus, hypothyroidism requiring only hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are eligible to participate.
* Receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the Investigator, increase the risk of serious neutropenic complications. Participants receiving replacement therapy of 10 mg of prednisone (or the equivalent hydrocortisone dose) per day are eligible.
* Receipt of live vaccines within 30 days prior to the first dose of study treatment or while on active treatment within the trial. (examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are permitted. However, intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines and are not permitted).COVID-19 vaccines are permitted.
* Any significant medical condition, laboratory abnormality or psychiatric illness that would limit the participant's ability to comply with study requirements.
* Participants that discontinued previous treatment for pancreatic adenocarcinoma due to a treatment-related ≥ Grade 3 toxicity.

  o For toxicity ≤ Grade 3, AE(s) must resolve to Grade 1 or baseline in order to be considered eligible for this trial.
* Participants that have received allogenic bone marrow or solid organ transplants are excluded.
* Participants that are pregnant, planning on becoming pregnant, or are breast feeding.

Primary outcomes:
measure: Overall Survival
timeFrame: 0 weeks
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: From initiation of therapy to clinically determined disease progression or death due to any cause, whichever came first, assessed up to 24 months.
measure: Performance Status
timeFrame: From screening through study completion, an average of 2 years.
measure: Overall Response Rate (ORR)
timeFrame: From initiation of treatment to clinically determined tumor size reduction for a minimum of 4 weeks
measure: Duration of Overall Response Rate (ORR)
timeFrame: 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.
measure: Duration of Clinical Benefit
timeFrame: From screening through last dose of therapy, assessed up to 24 months.
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego (UCSD) - Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center
state: California
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan - Rogel Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center (MCCC)
state: Minnesota
city: Saint Louis
country: United States
facility: Siteman Cancer Center - Washington University Medical Campus
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico Comprehensive Cancer Center
state: New Mexico
city: New York
country: United States
facility: New York University Langone Medical Center - Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Evelyn H. Lauder Breast Center - Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Physicians - Solid Tumor/Gastrointestinal Oncology
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania - Abramson Cancer Center
state: Pennsylvania
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University School of Medicine
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Hospital & Seattle Medical Center
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
References:
citation: 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.