Clinical Trials /

Modified Immune Cells (Autologous Dendritic Cells) and a Vaccine (Prevnar) After High-Dose External Beam Radiation Therapy in Treating Patients With Unresectable Liver Cancer

NCT03942328

Description:

This early phase I trial studies the side effects of autologous dendritic cells and a vaccine called Prevnar in treating patients with liver cancer that cannot be removed by surgery after undergoing standard high-dose external beam radiotherapy. Autologous dendritic cells are immune cells generated from patients' own white blood cells that are grown in a special lab and trained to stimulate the immune system to destroy tumor cells. A pneumonia vaccine called Prevnar may also help stimulate the immune system. Giving autologous dendritic cells and Prevnar to patients with liver cancer after radiotherapy may help doctors determine if it is possible to stimulate the body's own immune system to fight against the tumor, and to see if this immune stimulation can be done safely.

Related Conditions:
  • Hepatocellular Carcinoma
  • Intrahepatic Cholangiocarcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Modified Immune Cells (Autologous Dendritic Cells) and a Vaccine (Prevnar) After High-Dose External Beam Radiation Therapy in Treating Patients With Unresectable Liver Cancer
  • Official Title: Pilot Study of Intratumoral Injection of Dendritic Cells After High-Dose Conformal External Beam Radiotherapy in Patients With Unresectable Liver Cancer

Clinical Trial IDs

  • ORG STUDY ID: MC1641
  • SECONDARY ID: NCI-2019-02452
  • SECONDARY ID: MC1641
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT03942328

Conditions

  • Stage III Hepatocellular Carcinoma AJCC v8
  • Stage III Intrahepatic Cholangiocarcinoma AJCC v8
  • Stage IIIA Hepatocellular Carcinoma AJCC v8
  • Stage IIIA Intrahepatic Cholangiocarcinoma AJCC v8
  • Stage IIIB Hepatocellular Carcinoma AJCC v8
  • Stage IIIB Intrahepatic Cholangiocarcinoma AJCC v8
  • Stage IV Hepatocellular Carcinoma AJCC v8
  • Stage IV Intrahepatic Cholangiocarcinoma AJCC v8
  • Stage IVA Hepatocellular Carcinoma AJCC v8
  • Stage IVB Hepatocellular Carcinoma AJCC v8
  • Unresectable Hepatocellular Carcinoma
  • Unresectable Intrahepatic Cholangiocarcinoma

Interventions

DrugSynonymsArms
Pneumococcal 13-valent Conjugate VaccinePCV 13, PCV13 Vaccine, Prevnar 13Treatment (EBRT, autologous dendritic cells, Prevnar)
Therapeutic Autologous Dendritic CellsTreatment (EBRT, autologous dendritic cells, Prevnar)

Purpose

This early phase I trial studies the side effects of autologous dendritic cells and a vaccine called Prevnar in treating patients with liver cancer that cannot be removed by surgery after undergoing standard high-dose external beam radiotherapy. Autologous dendritic cells are immune cells generated from patients' own white blood cells that are grown in a special lab and trained to stimulate the immune system to destroy tumor cells. A pneumonia vaccine called Prevnar may also help stimulate the immune system. Giving autologous dendritic cells and Prevnar to patients with liver cancer after radiotherapy may help doctors determine if it is possible to stimulate the body's own immune system to fight against the tumor, and to see if this immune stimulation can be done safely.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Evaluation of safety and tolerability of an autologous dendritic cell (DC) vaccine
      delivered by intra-tumoral injection in patients with primary liver cancer treated with
      high-dose conformal external beam radiotherapy (EBRT).

      SECONDARY OBJECTIVES:

      I. To assess feasibility in patients with liver cancer treated with high-dose conformal EBRT
      followed by autologous DC vaccine injection.

      II. To assess overall response rate in patients with liver cancer treated with high-dose
      conformal EBRT followed by autologous DC vaccine injection.

      III. To assess progression free survival in patients with liver cancer treated with high-dose
      conformal EBRT followed by autologous DC vaccine injection.

      IV. To assess clinical benefit rate in patients with liver cancer treated with high-dose
      conformal EBRT followed by autologous DC vaccine injection.

      V. To assess time to response in patients with liver cancer treated with high-dose conformal
      EBRT followed by autologous DC vaccine injection.

      VI. To assess duration of response in patients with liver cancer treated with high-dose
      conformal EBRT followed by autologous DC vaccine injection.

      VII. To assess overall survival in patients with liver cancer treated with high-dose
      conformal EBRT followed by autologous DC vaccine injection.

      RADIOLOGIC STUDY OBJECTIVES:

      I. To assess the radiologic response over time of primary liver tumors treated with high-dose
      conformal EBRT followed by autologous DC vaccine injection.

      CORRELATIVE RESEARCH OBJECTIVES:

      I. To monitor patients? immune response after vaccine therapy. II. To assess the immune
      response to pneumococcal 13-valent conjugate vaccine (Prevnar).

      OUTLINE:

      Patients undergo standard of care high-dose EBRT for 5 or 15 fractions over 1-3 weeks (cycle
      1). Patients then receive autologous dendritic cells intratumorally (IT) on day 1 of cycles
      1-7, and pneumococcal 13-valent conjugate vaccine intramuscularly (IM) on day 1 of cycles 1-3
      only. Treatment repeats every 28 days for up to 7 cycles in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 2 weeks and then every 3
      months for 1 year (beginning at week 36 or 12 weeks after last autologous dendritic cell dose
      whichever is earlier). Patients are then followed every 3 months until disease progression,
      and then every 6 months until 5 years after registration.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (EBRT, autologous dendritic cells, Prevnar)ExperimentalPatients undergo standard of care high-dose EBRT for 5 or 15 fractions over 1-3 weeks (cycle 1). Patients then receive autologous dendritic cells IT on day 1 of cycles 1-7, and pneumococcal 13-valent conjugate vaccine IM on day 1 of cycles 1-3 only. Treatment repeats every 28 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity.
  • Pneumococcal 13-valent Conjugate Vaccine
  • Therapeutic Autologous Dendritic Cells

Eligibility Criteria

        Inclusion Criteria:

          -  Histological and/or radiologic confirmation of hepatocellular carcinoma (HCC) OR
             histologic confirmation of intrahepatic cholangiocarcinoma (CCA)

          -  The following tumor characteristics must be met

               -  Unresectable HCC or intrahepatic CCA

               -  Measurable or evaluable disease

               -  All lesions should be treatable by EBRT while meeting normal tissue constraints

               -  Tumor lesions should be accessible using an ultrasound (US) guided approach for
                  intratumoral DC injection

               -  Patients are required to have no evidence of extrahepatic tumor (excluding tumor
                  thrombus) by computed tomography (CT) or magnetic resonance imaging (MRI) scan

                    -  NOTE: Patients who are not candidates for surgical treatment or for ablation
                       with curative intent are allowed

          -  Good candidate for standard of care high-dose conformal EBRT in the view of the
             investigator

          -  Eastern Cooperative Oncology Group( ECOG) performance status (PS) 0 or 1

          -  Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to
             registration)

          -  Absolute lymphocyte count (ALC) >= 500/mm^3 (obtained =< 14 days prior to
             registration)

          -  Absolute monocyte count (AMC) >= 300/mm^3 (obtained =< 14 days prior to registration)

          -  Platelet count >= 50,000/mm^3 (obtained =< 14 days prior to registration)

          -  Hemoglobin >= 9.0 g/dL (obtained =< 14 days prior to registration)

          -  Total bilirubin < 3 mg/dL (obtained =< 14 days prior to registration)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 x upper limit
             of normal (ULN) ( obtained =< 14 days prior to registration)

          -  Creatinine =< 2 mg/dL (obtained =< 14 days prior to registration)

          -  Prothrombin time/International Normalized Ratio (PT/ INR) =< 1.5 x ULN (obtained =< 14
             days prior to registration)

          -  Negative pregnancy test done =< 7 days prior to registration, for persons of
             childbearing potential only

          -  Ability to provide written consent

          -  Willingness to return to enrolling institution for follow-up (during the active
             monitoring phase of the study)

          -  Willingness to provide blood and tissue samples for correlative research purposes

        Exclusion Criteria:

          -  Any of the following because this study involves an investigational agent whose
             genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
             unknown:

               -  Pregnant persons

               -  Nursing persons

               -  Persons of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
             positive and currently receiving antiretroviral therapy.

               -  NOTE: Patients known to be HIV positive, but without clinical evidence of an
                  immunocompromised state, are eligible for this trial

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Receiving any other investigational agent that would be considered a treatment for the
             primary neoplasm

          -  Other active malignancy =< 3 years prior to registration. EXCEPTIONS: Non-melanotic
             skin cancer or carcinoma-in-situ of the cervix

               -  NOTE: If there is a history of prior malignancy, they must not be receiving other
                  specific treatment for their cancer

          -  Major surgery =< 4 weeks prior to enrollment (other than diagnostic surgery or
             surgical spacer placement in preparation for radiation treatment)

          -  History of hypersensitivity or anaphylactoid reactions to pneumococcal vaccine or any
             component of the formulation, including diphtheria toxoid

          -  Active autoimmune disease such as autoimmune hepatitis, Crohn?s disease, rheumatoid
             arthritis, Sjogren's disease, systemic lupus erythematosus, or similar conditions

          -  Requires coagulopathy treatment (INR > 1.5) or use of anti-platelet agents that cannot
             be discontinued for the intratumoral injection procedure

               -  NOTE: Heparin for line patency without detectable lab abnormalities in
                  coagulation will be allowed

          -  Corticosteroids =< 2 weeks prior to registration, including oral, intravenous (IV),
             subcutaneous, or inhaled routes of administration

               -  NOTE: Patients on chronic corticosteroids for adrenal insufficiency or other
                  reasons may enroll if they receive less than 10 mg/day of prednisone (or
                  equivalent)

          -  History of myocardial infarction =< 6 months, or congestive heart failure requiring
             use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

          -  Child Pugh class B or C cirrhosis of the liver

          -  Previously received immune modulating therapies including but not limited to immune
             checkpoint inhibitors targeting PD-1 PDL-1 CTLA4, etc; or prior dendritic cell therapy

          -  Prior liver radiation, including radioembolization

          -  Barcelona Clinic Liver Cancer (BCLC) stage D disease
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of significant toxicity
Time Frame:Up to 1 year post treatment
Safety Issue:
Description:A significant toxicity is defined as a dose limiting toxicity that is possibly, probably, or definitely related to DC treatment. Toxicities will be assessed using the Cancer Therapy Evaluation Program active version of the Common Terminology Criteria for Adverse Events.

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:Up to 1 year post treatment
Safety Issue:
Description:The overall response rate will be estimated by the number of patients with an objective status of complete response (CR) or partial response (PR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
Measure:Number of patients who received at least one dose of intratumoral DC injection
Time Frame:Up to 1 year post treatment
Safety Issue:
Description:The feasibility of the regimen will be estimated by the number of patients who received at least one dose of intratumoral DC injection divided by the total number of patients who received apheresis.
Measure:Clinical benefit rate
Time Frame:Up to 1 year post treatment
Safety Issue:
Description:The clinical benefit rate will be estimated by the number of patients with an objective status of stable disease or CR or PR at any time divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true clinical benefit rate will be calculate
Measure:Time to response
Time Frame:Up to 1 year post treatment
Safety Issue:
Description:Time to response is defined for all evaluable patients who have achieved an objective response as the date of initiation of vaccination treatment to the date at which the patient?s objective status is first noted to be either a CR or PR. Time to response will be summarized descriptively using Kaplan-Meier methodology.
Measure:Duration of response
Time Frame:Up to 1 year post treatment
Safety Issue:
Description:Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient?s objective status is first noted to be either a CR or PR to the earliest date progression is documented. Duration of response will be summarized descriptively using Kaplan-Meier methodology.
Measure:Overall survival
Time Frame:From registration to death from any cause, assessed up to 5 years after registration
Safety Issue:
Description:Kaplan-Meier methodology will be used to estimate the survival over time.
Measure:Progression-free survival
Time Frame:From registration to the first of either disease progression or death from any cause, assessed up to 5 years after registration
Safety Issue:
Description:Kaplan-Meier methodology will be used to estimate the progression-free survival over time.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

Last Updated

June 13, 2019