Precision Promise Platform Trial for Metastatic Pancreatic Cancer
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 1st and/or 2nd line metastatic pancreatic cancer patients and determine which, if any, patients benefit from each investigational arm. Secondary Objectives - To determine short and long-term safety signals of each investigational arm in pancreatic cancer patients vs. SOC. - To determine progression-free survival (PFS) for each investigational arm vs. SOC. - Rates of overall response, CR, and PR; duration of overall response, CR or PR (whichever occurs first). - Rate of clinical benefit; duration of clinical benefit.
18 Years and up
Accepting Healthy Volunteers?
A subject will be eligible to participate in Precision PromiseSM if all the below inclusion criteria are met:
1. Age ≥ 18 years
2. Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma (PDAC) and eligible for treatment in the first line or second line settings. Note: prior adjuvant or neoadjuvant chemotherapy is permitted if the last dose was >12 months prior and all the other conditions below are met.
3. Radiographically measurable disease of at least one site by computed tomography (CT) scan (or magnetic resonance imaging, if allergic to CT contrast media) 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.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
5. Adequate organ function (lab results must be obtained within the 28-day window prior to randomization)
1. Absolute neutrophil count ≥ 1500/mm3
2. Hemoglobin ≥ the lower limit of normal (LLN) or 9g/dL
3. Platelets ≥ 100,000/mm
4. Serum creatinine ≤ 1.0 x upper limit normal (ULN), or calculated creatinine clearance ≥ 60 mL/min (Cockcroft Gault)
5. Albumin ≥ 3.0 g/dL
6. 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).
7. Total bilirubin ≤ 1.5 x ULN
8. INR ≤ 1.5 x ULN
6. Consent to provide protocol-mandated tissue and blood samples for diagnostic and research purposes.
7. Able to swallow pills, capsules or tablets.
8. Able to adhere to study visit schedule and other protocol requirements.
9. 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:
1. 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.
2. 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.
10. 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.
11. Understands the nature of the study and has agreed to participate by voluntarily signing the IRB approved informed consent.
1. A subject will not be eligible to participate in Precision PromiseSM if any of the following criteria are met:
a) Received any therapy within 28 days (or 5 half-lives, whichever is shorter,) prior to randomization.
2. History of allergy or hypersensitivity to any of the study treatments or any of their excipients.
3. Pre-existing peripheral neuropathy > Grade 1, as defined by CTCAE V 4.03.
4. Known history of hepatitis B, HIV or active hepatitis C infection.
5. Note: HIV testing is not required in the absence of clinical suspicion
6. Serious, non-healing wound, ulcer, bone fracture, or abscess.
7. The inability to swallow pills, capsules or tablets.
8. Subjects who received a combination of two investigational agents as part of first-line therapy (novel + novel) are excluded. Subjects who received one investigational agent or one investigational agent combined with an FDA approved chemotherapy regimen in first line will be allowed to be enrolled in Precision PromiseSM for second line therapy.
9. Any secondary malignancy that required chemotherapy treatment in the past two years
10. History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
11. QTc > 450 msec if male and QTc > 470 msec if female.
12. 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], requirement for inotropic support or use of devices for cardiac conditions [pacemakers/defibrillators]).
13. 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).
14. Active, known or suspected autoimmune disease, including systemic lupus erythematosus, Hashimotos thyroiditis, scleroderma, polyarteritis nodosa or autoimmune hepatitis.
a) 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.
15. Receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the Investigator, increase the risk of serious neutropenic complications.
16. 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).
17. Any significant medical condition, laboratory abnormality or psychiatric illness that would limit the subject's ability to comply with study requirements.
18. Subjects that discontinued previous treatment for pancreatic adenocarcinoma due to a treatment-related Grade 3 toxicity.
1. For toxicity discontinuations < Grade 3, AE(s) must resolve to Grade 1 or baseline in order to be considered eligible for this trial.