Clinical Trials /

NBTXR3 Activated by Radiation Therapy for the Treatment of Locally Advanced or Borderline-Resectable Pancreatic Cancer

NCT04484909

Description:

The purpose of this Phase I study is to determine the recommended phase 2 dose (RP2D) and safety profile of NBTXR3 activated by radiation therapy for the treatment of patients with pancreatic cancer that has spread to nearby tissues or lymph nodes (locally advanced) or may be able to be removed by surgery (borderline-resectable). NBTXR3 is a drug that when activated by radiation therapy, may cause targeted destruction of cancer cells. Radiation therapy uses high energy to kill cancer cells and shrink tumors. Giving NBTXR3 followed by radiation therapy may work better to treat locally advanced or borderline-resectable pancreatic cancer compared to radiation therapy alone.

Related Conditions:
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: NBTXR3 Activated by Radiation Therapy for the Treatment of Locally Advanced or Borderline-Resectable Pancreatic Cancer
  • Official Title: Phase I Study of NBTXR3 Activated by Radiotherapy for Locally Advanced or Borderline Resectable Pancreatic Ductal Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: 2019-1001
  • SECONDARY ID: NCI-2020-03731
  • SECONDARY ID: 2019-1001
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT04484909

Conditions

  • Borderline Resectable Pancreatic Adenocarcinoma
  • Locally Advanced Pancreatic Ductal Adenocarcinoma
  • Resectable Pancreatic Ductal Adenocarcinoma
  • Stage III Pancreatic Cancer AJCC v8

Purpose

The purpose of this Phase I study is to determine the recommended phase 2 dose (RP2D) and safety profile of NBTXR3 activated by radiation therapy for the treatment of patients with pancreatic cancer that has spread to nearby tissues or lymph nodes (locally advanced) or may be able to be removed by surgery (borderline-resectable). NBTXR3 is a drug that when activated by radiation therapy, may cause targeted destruction of cancer cells. Radiation therapy uses high energy to kill cancer cells and shrink tumors. Giving NBTXR3 followed by radiation therapy may work better to treat locally advanced or borderline-resectable pancreatic cancer compared to radiation therapy alone.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To determine the recommended phase II dose (RP2D) of hafnium oxide nanoparticles NBTXR3
      (NBTXR3) activated by radiation therapy (RT) (hereafter referred to R3/RT).

      SECONDARY OBJECTIVES:

      I. To evaluate the anti-tumor response of R3/RT. II. To evaluate the safety and feasibility
      of R3/RT. III. To evaluate time-to-event outcomes.

      EXPLORATORY OBJECTIVES:

      I. To evaluate the body kinetic profile of intratumorally injected NBTXR3. II. To evaluate
      time to event outcomes for subjects with clinical staging of locally advanced, unresectable
      disease.

      III. To evaluate resectability conversion rates. IV. To evaluate surgical outcomes in
      subjects who undergo surgery after radiation therapy.

      V. To associate radiomic measurements with outcomes. VI. To evaluate biomarkers of response
      in subjects treated with R3/RT.

      OUTLINE: This is a dose-escalation study of NBTXR3.

      Patients receive NBTXR3 intratumorally (IT) on day 1. Patients then undergo 15 fractions of
      intensity modulated radiation therapy (IMRT) between days 15-43 in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 1 month and then every 3
      months for up to 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (NBTXR3, radiation therapy)ExperimentalPatients receive NBTXR3 IT on day 1. Patients then undergo 15 fractions of radiation therapy between days 15-43 in the absence of disease progression or unacceptable toxicity.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Signed informed consent form (ICF) indicating that participant understands the purpose
                 of, and procedures required for, the study and is willing to participate in the study
    
              -  Biopsy proven ductal adenocarcinoma of the pancreas as defined by the following:
    
                   -  Borderline resectable pancreatic adenocarcinoma (BRPC) has no aortic involvement
                      with at least ONE of the following features:
    
                        -  Superior mesenteric vein (SMV) or portal vein (PV) with a tumor interface of
                           >= 180 degrees OR short segment occlusion amenable to reconstruction
    
                        -  Superior mesenteric artery (SMA) or celiac axis (CA) with a tumor interface
                           of < 180 degrees
    
                        -  Any degree of hepatic artery interface this is amenable to reconstruction
    
                   -  Locally advanced pancreatic adenocarcinoma (LAPC) has at least ONE of the
                      following features:
    
                        -  Occlusion of the SMV or PV that is not amenable to reconstruction
    
                        -  Tumor interface of the SMA or CA >= 180 degrees
    
                        -  Involvement of the hepatic artery that is not amenable to reconstruction
    
                        -  Aortic involvement
    
              -  Has had a 4-month course (+/- 2-months) of chemotherapy for PDAC without radiographic
                 evidence of metastatic disease. Following chemotherapy regimens are allowed:
    
                   -  Gemcitabine/nab-paclitaxel
    
                   -  Gemcitabine/capecitabine
    
                   -  Gemcitabine/cisplatin
    
                   -  Gemcitabine
    
                   -  Leucovorin calcium, fluorouracil and oxaliplatin (FOLFOX)
    
                   -  Fluorouracil, irinotecan, leucovorin and oxaliplatin (FOLFIRINOX)
    
              -  Amenable to undergo the endoscopic ultrasound guided injection of NBTXR3 as per
                 investigator or treating physician
    
              -  Has a target lesion in the pancreas that is identifiable on cross sectional imaging by
                 repeated measurements (via Response Evaluation Criteria for Solid Tumors [RECIST
                 v1.1]) at the same anatomical location
    
                   -  Nodal disease only is not allowed
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1
    
              -  Hemoglobin >= 8.0 g/dL (at screening)
    
              -  Absolute neutrophil count (ANC) >= 1,500/mm^3 (at screening)
    
              -  Platelet count >= 100,000/mm^3 (at screening)
    
              -  Creatinine =< 1.5 x upper limit of normal (ULN) (at screening)
    
              -  Total bilirubin =< 2.0 mg/dL (at screening)
    
              -  Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 2.5 x upper limit
                 of normal (ULN) (at screening)
    
              -  Negative pregnancy test =< 7 days prior to NBTXR3 injection in all females of
                 child-bearing potential
    
              -  If participant has a history of prior duodenal or biliar plastic stent, it should be
                 replaced with a metal stent >= 1 weeks prior to study day 1
    
            Exclusion Criteria:
    
              -  Prior radiation therapy to the upper abdomen
    
              -  Prior surgical resection of pancreatic tumor
    
              -  Diagnosis other than pancreatic ductal adenocarcinoma. All other histologic types
                 (i.e., adenosquamous, cystadenocarcinoma, etc.) are not eligible to participate on
                 this study
    
              -  LAPC or BRPC with radiographic evidence of metastasis at screening
    
              -  Receiving any approved or investigational anti-neoplastic agent other than the
                 chemotherapies specified in this protocol (i.e., chemotherapies listed above)
    
              -  Known uncontrolled (grade >= 2) or active gastric or duodenal ulcer disease within 30
                 days of enrollment
    
              -  Known contraindication to iodine-based or gadolinium-based intravenous (IV) contrast
    
              -  Active malignancy, in addition to pancreatic cancer, with the exception of basal cell
                 carcinoma of the skin definitively treated and relapse free within at least 1 year
                 since diagnosis
    
              -  Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular
                 fibrillation, torsades de pointes, second or third degree atrioventricular heart block
                 without a permanent pacemaker in place)
    
              -  Class III or IV congestive heart failure as defined by the New York Heart Association
                 functional classification system < 6 months prior to screening
    
              -  Known active, uncontrolled (high viral load) human immunodeficiency virus (HIV),
                 hepatitis B or hepatitis C infection
    
                   -  Patients who have been vaccinated for hepatitis B and do not have a history of
                      infection are eligible
    
              -  Female patients who are pregnant or breastfeeding
    
              -  Women of child-bearing potential and their male partners who are unwilling or unable
                 to use an acceptable method of birth control to avoid pregnancy for the entire study
                 period. Acceptable methods of contraception are those that, alone or in combination,
                 result in a failure rate of < 1% per year when used consistently and correctly
    
              -  Any condition for which, in the opinion of the investigator, participation would not
                 be in the best interest of the participant (e.g., compromise the well-being) or that
                 could prevent, limit, or confound the protocol-specified assessments
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Dose-limiting toxicities
    Time Frame:4 weeks after last radiation dose
    Safety Issue:
    Description:Any grade >= 3 adverse event related to NBTXR3 and/or radiation therapy. Any toxicity (grade >= 3) that is at least possibly related to study drug (NBTXR3) is a DLT. Adverse events will be scored based on National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE v 5.0).

    Secondary Outcome Measures

    Measure:Determination of the feasibility of NBTXR3 injection in pancreas
    Time Frame:Up to 1 year
    Safety Issue:
    Description:Feasibility refers to the ability to do intratumoral injection of NBTXR3. The outcome for each patient would be "feasible" or "not feasible."
    Measure:Progression free survival (PFS)
    Time Frame:From NBTXR3 injection to local recurrence, local progression, distant progression, or death from any cause, whichever occurs first, assessed up to 1 year
    Safety Issue:
    Description:
    Measure:Overall survival (OS)
    Time Frame:From NBTXR3 injection to death from any cause or EoS, whichever occurs first, assessed up to 1 year
    Safety Issue:
    Description:

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:M.D. Anderson Cancer Center

    Last Updated

    July 20, 2020