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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/16/2021.

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

Clinicaltrials.gov identifier NCT03942328

Recruitment Status Recruiting

First Posted May 8, 2019

Last update posted September 1, 2020

Study Description

Brief summary:

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.

  • Condition or Disease: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 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
    Stage IIIB Hepatocellular Carcinoma AJCC v8
    Stage IIIB Intrahepatic Cholangiocarcinoma AJCC v8
  • Intervention/Treatment: Radiation: External Beam Radiation Therapy
    Biological: Pneumococcal 13-valent Conjugate Vaccine
    Biological: Therapeutic Autologous Dendritic Cells
  • Phase: Early Phase 1
Detailed Description

PRIMARY OBJECTIVE: 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 OBJECTIVE: 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 2-8, and pneumococcal 13-valent conjugate vaccine intramuscularly (IM) on day 1 of cycles 2-4 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.

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 26 participants
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: Pilot Study of Intratumoral Injection of Dendritic Cells After High-Dose Conformal External Beam Radiotherapy in Patients With Unresectable Liver Cancer
  • Actual Study Start Date: May 2019
  • Estimated Primary Completion Date: May 2022
  • Estimated Study Completion Date: May 2022
Arms and interventions
Arm Intervention/treatment
Experimental: Treatment (EBRT, autologous dendritic cells, Prevnar)
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 IT on day 1 of cycles 2-8, and pneumococcal 13-valent conjugate vaccine IM on day 1 of cycles 2-4 only. Treatment repeats every 28 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity.
Radiation: External Beam Radiation Therapy
Undergo high-dose EBRT

Biological: Pneumococcal 13-valent Conjugate Vaccine
Given IM

Biological: Therapeutic Autologous Dendritic Cells
Given IT
Outcome Measures
  • Primary Outcome Measures: 1. Incidence of significant toxicity [ Time Frame: Up to completion of cycle 2 (each cycle is 28 days) ]
    A significant toxicity is defined as a dose limiting toxicity that is possibly, probably, or definitely related to dendritic cell (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: 1. Overall survival [ Time Frame: From registration to death from any cause, assessed up to 5 years after registration ]
    Kaplan-Meier methodology will be used to estimate the survival over time.
  • 2. Overall response rate [ Time Frame: Up to 1 year post treatment ]
    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.
  • 3. Number of patients who received at least one dose of intratumoral DC injection [ Time Frame: Up to 1 year post treatment ]
    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.
  • 4. Clinical benefit rate [ Time Frame: Up to 1 year post treatment ]
    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
  • 5. Time to response [ Time Frame: Up to 1 year post treatment ]
    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.
  • 6. Duration of response [ Time Frame: Up to 1 year post treatment ]
    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.
  • 7. 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 ]
    Kaplan-Meier methodology will be used to estimate the progression-free survival over time.
  • Other Outcome Measures: 1. Change in target lesion measurements [ Time Frame: Baseline up to 1 year post treatment ]
    All enhancing lesions will be evaluated over time for each patient. The percent change from baseline in target lesion measurements will be assessed over time. Differences in values over time will be summarized descriptively and graphically.
  • 2. Change in immunologic correlates before and after vaccination treatment [ Time Frame: Baseline up to 1 year post treatment ]
    Change in immunologic correlates before and after vaccination treatment will be evaluated and summarized both quantitatively and graphically. Each of the correlative endpoints will be summarized individually, but will also be evaluated in terms of their relationships to one another; i.e., will use Spearman rank correlation coefficient to assess the correlations between baseline levels as well as between changes before and after treatment in these immunologic markers. In addition, these immunologic markers will be correlated with cancer and treatment related outcomes (e.g. response, adverse events). Relationships will also be explored graphically using scatter plots.
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
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 == 500/mm^3 (obtained == 300/mm^3 (obtained == 50,000/mm^3 (obtained == 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 = 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

Contacts and Locations
Contacts
Locations

United States, Minnesota
Mayo Clinic in Rochester
Rochester

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Principal Investigator: Lewis R Roberts Mayo Clinic in Rochester

More Information
  • Responsible Party: Mayo Clinic
  • ClinicalTrials.gov Identifier: NCT03942328 History of Changes
  • Other Study ID Numbers: MC1641, NCI-2019-02452, MC1641, P30CA015083
  • First Posted: May 8, 2019 Key Record Dates
  • Last Update Posted: September 1, 2020
  • Last Verified: August 2020
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Additional relevant MeSH terms: Carcinoma, Hepatocellular
    Liver Neoplasms
    Cholangiocarcinoma
    Carcinoma