Clinical Trials /

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

NCT04229004

Description:

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.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Multi-center Trial to Evaluate Multiple Regimens in Metastatic Pancreatic Cancer
  • Official Title: Precision PromiseSM Platform Trial for Metastatic Pancreatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: PanCAN_Precision PromiseSM
  • NCT ID: NCT04229004

Conditions

  • Metastatic Pancreatic Cancer
  • Metastatic Pancreatic Adenocarcinoma

Interventions

DrugSynonymsArms
DoseGemcitabine combined with nab-paclitaxel
Dose -SM-88SM-88
Dose -mFOLFIRINOXmFOLFIRINOX

Purpose

Precision PromiseSM 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.

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 rapidly and efficiently test
      multiple novel drugs and combinations compared to standard of care therapy in first and
      second metastatic patients. Bayesian response-adaptive randomization will be used to assign
      patients to arms based on their performance in subtypes of the disease. The primary endpoint
      is overall survival.
    

Trial Arms

NameTypeDescriptionInterventions
Gemcitabine combined with nab-paclitaxelOtherThe 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.
  • Dose
SM-88Experimental460 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.
  • Dose -SM-88
mFOLFIRINOXOtherOxaliplatin 85 mg/m2, Leucovorin 400 mg/m2, Irinotecan 150 mg/m2, 5-Fluorouracil 2400 mg/m2 46-48 hour infusion
  • Dose -mFOLFIRINOX

Eligibility Criteria

        Inclusion Criteria:

        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.

        Exclusion Criteria:

          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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival
Time Frame:0 weeks
Safety Issue:
Description:Overall survival (OS) is defined from the time of initiation of treatment until death due to any cause. Subjects still alive at the time of an analysis will be considered censored at their date of last contact.

Secondary Outcome Measures

Measure:Progression free survival (PFS)
Time Frame:From initiation of therapy to clinically determined disease progression or death due to any cause, whichever came first, assessed up to 24 months.
Safety Issue:
Description:PFS will be presented with probability that the hazard ratio is less than 1.0 as well as the corresponding Kaplan-Meier curves and the log-rank test for the comparison with controls.
Measure:Performance Status
Time Frame:From screening through study completion, an average of 2 years.
Safety Issue:
Description:Changes in Performance Status will be evaluated using the Eastern Cooperative Oncology Group (ECOG) Performance Status, where the highest value is 0 (patient is fully active) and the lowest value is 5 (patient is deceased).
Measure:Overall Response Rate (ORR)
Time Frame:From initiation of treatment to clinically determined tumor size reduction for a minimum of 4 weeks
Safety Issue:
Description:ORR is defined as the portion of subjects on an arm with a tumor size reduction of at least 30%.
Measure:Duration of Overall Response Rate (ORR)
Time Frame: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.
Safety Issue:
Description:Duration of ORR is defined as the time from the date of response to the date of clinically determined disease progression or death due to any cause.
Measure:Duration of Clinical Benefit
Time Frame:From screening through last dose of therapy, assessed up to 24 months.
Safety Issue:
Description:Duration of Clinical Benefit will be evaluated using a composite of measures including patient reported outcomes (PROs), supportive care regimens, and disease status.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Pancreatic Cancer Action Network

Last Updated

January 14, 2020