| Eligibility |
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 (ß-human chorionic gonadotropin
[ß-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.
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