Clinical Trials /

QUILT-2.022 NANT-008 in Combination w/ 5-fluorouracil, Bevacizumab, Leucovorin & Oxaliplatin in Subjects With Pancreatic Cancer

NCT03127124

Description:

This is a phase 1b/2 study to evaluate the safety and efficacy of NANT-008 in combination with 5-fluorouracil, bevacizumab, leucovorin, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: QUILT-2.022 NANT-008 in Combination w/ 5-fluorouracil, Bevacizumab, Leucovorin & Oxaliplatin in Subjects With Pancreatic Cancer
  • Official Title: An Open-label, Multicenter, Single-arm, Phase 1b/2 Study of NANT-008 in Combination With 5-fluorouracil, Bevacizumab, Leucovorin, and Oxaliplatin in Patients With Metastatic Pancreatic Adenocarcinoma.

Clinical Trial IDs

  • ORG STUDY ID: QUILT-2.022
  • NCT ID: NCT03127124

Conditions

  • Pancreatic Adenocarcinoma Metastatic

Interventions

DrugSynonymsArms
NANT-008NANT-008 in combination with other agents
Fluorouracil Injectable ProductNANT-008 in combination with other agents
Avastin Injectable ProductNANT-008 in combination with other agents
Leucovorin Calcium InjectionNANT-008 in combination with other agents
Eloxatin Injectable ProductNANT-008 in combination with other agents

Purpose

This is a phase 1b/2 study to evaluate the safety and efficacy of NANT-008 in combination with 5-fluorouracil, bevacizumab, leucovorin, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma.

Detailed Description

      Phase 1b is designed to evaluate the recommended phase 2 dose (RP2D) of NANT-008 and
      dose-limiting toxicities (DLTs) of NANT-008 in combination with metronomic 5-FU, bevacizumab,
      leucovorin, and oxaliplatin in subjects with advanced metastatic pancreatic carcinoma. In
      phase 2, subjects will receive the combination of RP2D of NANT-008 from phase 1b in
      combination with metronomic 5-FU, bevacizumab, leucovorin, and oxaliplatin. Phase 2 is
      designed to evaluate the efficacy of the tested regimen as assessed by 1-year survival rate
      in subjects with advanced metastatic pancreatic adenocarcinoma.
    

Trial Arms

NameTypeDescriptionInterventions
NANT-008 in combination with other agentsExperimentalNANT-008 will be administered in combination with 5-fluorouracil, bevacizumab, leucovorin, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma.
  • NANT-008
  • Fluorouracil Injectable Product
  • Avastin Injectable Product
  • Leucovorin Calcium Injection
  • Eloxatin Injectable Product

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female subject is between ≥ 18 and ≤ 65 years of age at the time of signing
             the informed consent form (ICF).

          2. Able to understand and provide a signed informed consent that fulfills the relevant
             IRB or IEC guidelines.

          3. Histologically confirmed, unresectable, locally advanced or metastatic pancreatic
             adenocarcinoma.

          4. ECOG performance status of 0 to 1.

          5. Have at least 1 measurable lesion and/or non-measurable disease evaluable according to
             RECIST Version 1.1.

          6. Have not received any prior treatment other than radiation therapy for symptomatic
             pain relief.

          7. Resolution of all toxic side effects of prior chemotherapy, radiotherapy, or surgical
             procedures to CTCAE grade ≤ 1, with the exception of alopecia.

          8. Must be willing to provide pre- and post-treatment blood samples for exploratory
             analyses.

          9. Ability to attend required study visits and return for adequate follow-up, as required
             by this protocol.

         10. Must have a recent FFPE tumor biopsy specimen following the conclusion of the most
             recent anticancer treatment and be willing to release the specimen for tumor molecular
             profiling analysis. If an historic specimen is not available, the subject must be
             willing to undergo a biopsy during the screening period.

         11. Agreement to practice effective contraception (both male and female subjects, if the
             risk of conception exists).

         12. Must have a stable, functioning stent at least 2 weeks before the beginning of the
             study (metal stents are preferred as per NCCN guidelines) if subject has had a
             previous biliary or pancreatic duct obstruction requiring stent placement.

        Exclusion Criteria:

          1. History of previous systemic chemotherapy or investigational therapy.

          2. History of other active malignancies or brain metastasis except: controlled basal cell
             carcinoma or squamous cell carcinoma; prior history of in situ cancer (eg, breast,
             melanoma, squamous cell carcinoma of the skin, cervical) and > 5 years without
             evidence of disease; prior history of prostate cancer that is not under active
             systemic treatment (except hormonal therapy) and with undetectable PSA (< 0.2 ng/mL).

          3. Inadequate organ function, evidenced by the following laboratory results:

               1. White blood cell (WBC) count < 3,500 cells/mm3

               2. Absolute neutrophil count < 1,500 cells/mm3.

               3. Platelet count < 100,000 cells/mm3.

               4. Hemoglobin < 9 g/dL.

               5. Total bilirubin greater than the upper limit of normal (ULN) at time of
                  enrollment; unless the subject has known history of Gilbert's syndrome.

               6. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT])
                  > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).

               7. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver
                  metastases, or >10 × ULN in subjects with bone metastases).

               8. Serum creatinine > 2.0 mg/dL or 177 μmol/L.

               9. International normalized ratio (INR) or activated partial thromboplastin time
                  (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN.

          4. Pre-existing peripheral neuropathy > grade 1 based on NCI CTCAE V4.03.

          5. Dihydropyrimidine dehydrogenase gene polymorphism (DPYD*2A) (must be tested prior to
             inclusion).

          6. Current chronic daily treatment (continuous for > 3 months) with systemic
             corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone),
             excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic
             reaction or anaphylaxis in subjects who have known contrast allergies is allowed.

          7. Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B
             virus (HBV), or hepatitis C virus (HCV).

          8. Undergone major surgery, other than diagnostic surgery (ie, surgery done to obtain a
             biopsy for diagnosis without removal of an organ), within 4 weeks prior to day 1 of
             treatment in this study or surgical wound has not fully healed.

          9. History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).

         10. Evidence of gastric ulcers, gastrointestinal fistulas, and gastrointestinal
             perforations.

         11. History of interstitial lung disease, history of slowly progressive dyspnea and
             unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary
             hypersensitivity pneumonitis or multiple allergies that in the opinion of the
             Investigator may put them at increased risk of interstitial pneumonitis.

         12. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) or
             clinically significant (ie, active) cardiovascular disease, cerebrovascular
             accident/stroke, or myocardial infarction within 6 months prior to first study
             medication; unstable angina; congestive heart failure of New York Heart Association
             grade 2 or higher; or serious cardiac arrhythmia requiring medication.

         13. Recent history of clinically significant hemoptysis.

         14. Known hypersensitivity to any component of the study medication(s).

         15. Pregnant and nursing women.

         16. Assessed by the investigator to be unable or unwilling to comply with the requirements
             of the protocol.

         17. Concurrent or prior use of a strong CYP3A4 inhibitor (including ketoconazole,
             itraconazole, posaconazole, clarithromycin, indinavir, nefazodone, nelfinavir,
             ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit products) or strong
             CYP3A4 inducers (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentin,
             phenobarbital, and St John's Wort) within 14 days before study day 1.

         18. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8
             inducer (rifampin) within 14 days before study day 1.
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1b Primary Endpoint
Time Frame:12 weeks
Safety Issue:
Description:Determine the recommended phase 2 dose (RP2D) of NANT-008 and dose-limiting toxicities (DLTs) of NANT-008

Secondary Outcome Measures

Measure:Phase 1b Secondary Endpoint
Time Frame:12 weeks
Safety Issue:
Description:To determine overall safety profile of the combination treatment
Measure:Phase 2 Secondary Endpoint
Time Frame:1 year
Safety Issue:
Description:Obtain additional data on the safety and tolerance of this study treatment at the RP2D
Measure:Phase 2 Secondary Endpoint
Time Frame:1 year
Safety Issue:
Description:Obtain preliminary data on the Objective response rate (ORR)
Measure:Phase 2 Secondary Endpoint
Time Frame:1 year
Safety Issue:
Description:Obtain preliminary data on the Progression-free survival (PFS)
Measure:Phase 2 Secondary Endpoint
Time Frame:1 year
Safety Issue:
Description:Obtain preliminary data on the Overall survival (OS)
Measure:Phase 2 Secondary Endpoint
Time Frame:1 year
Safety Issue:
Description:Obtain preliminary data on the Duration of Response (DOR)
Measure:Phase 2 Secondary Endpoint
Time Frame:1 year
Safety Issue:
Description:Obtain preliminary data on the Patient-reported outcomes (PROs) of pancreatic cancer symptoms.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NantPharma, LLC

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