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

This is an interventional treatment trial for Metastatic Pancreatic Cancer Read More

Inclusion Criteria

A subject will be eligible to participate in Precision PromiseSM 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 of at least one site 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 21-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 21-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 subjects on anticoagulation therapy).
• Subjects 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.

• Females of childbearing potential [defined as a sexually mature woman who (1) has not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or (2) has 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 heterosexual contact or agree to use medical doctor-approved contraception throughout the study without interruption while receiving study treatment and for at least 6 months following last dose of study treatment.
• Males must practice complete abstinence or agree to use a condom (even if he has undergone a successful vasectomy) during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 6 months following last dose of study treatment.
• HIV-infected subjects 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).
• HBV-infected subjects 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).
• Subjects with a history of hepatitis C virus (HCV) infection must have been treated and cured. Subjects with 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).
• Subjects 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.
• Subjects 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. Subjects receiving any active therapy for a concurrent secondary malignancy are excluded.
• Subjects 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, subjects 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 subject will not be eligible to participate in Precision PromiseSM 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 a concurrent secondary malignancy. Subjects 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].
• Subjects 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. Subjects 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., subjects 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 Subjects 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. Subjects 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).
• Any significant medical condition, laboratory abnormality or psychiatric illness that would limit the subject's ability to comply with study requirements.

• Subjects that discontinued previous treatment for pancreatic adenocarcinoma due to a treatment-related ≥ Grade 3 toxicity.

  • For toxicity ≤ Grade 3, AE(s) must resolve to Grade 1 or baseline in order to be considered eligible for this trial.
  • Subjects that have received allogenic bone marrow or solid organ transplants are excluded.