RECRUITING

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

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Conditions

Stage III Hepatocellular Carcinoma AJCC v8Stage III Intrahepatic Cholangiocarcinoma AJCC v8Stage IV Hepatocellular Carcinoma AJCC v8Stage IV Intrahepatic Cholangiocarcinoma AJCC v8Unresectable Hepatocellular CarcinomaUnresectable Intrahepatic Cholangiocarcinoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This early phase I trial studies the side effects of autologous dendritic cells and a vaccine called Prevnar in combination with immune checkpoint inhibition (with bevacizumab and atezolizumab or atezolizumab and tiragolumab) in treating patients liver cancer that cannot be removed by surgery (unresectable) 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. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Immunotherapy with monoclonal antibodies, such as atezolizumab and tiragolumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving autologous dendritic cells and Prevnar in combination with immune checkpoint inhibition after radiotherapy may be safe, and tolerable and may stimulate the body's own immune system to fight against the tumor in patients with unresectable liver cancer.

Official Title

MC1641 Phase II Study Of Intratumoral Injection Of Autologous Dendritic Cells Combined With Immune Checkpoint Inhibition After High-Dose Conformal External Beam Radiotherapy In Patients With Unresectable Primary Liver Cancer

Quick Facts

Study Start:2019-09-19
Study Completion:2028-02-29
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT03942328

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Age \>= 18 years
  2. * Pilot study (group 1): Histologic confirmation of intrahepatic CCA (Closed as of amendment 3)
  3. * Phase II study (group 2): Histologic and/or radiologic confirmation of hepatocellular carcinoma (HCC)
  4. * Phase II study (group 3): Histologic confirmation of intrahepatic cholangiocarcinoma (iCCA)
  5. * The following tumor characteristics must be met
  6. * Unresectable disease: HCC (group 2) or intrahepatic CCA (group 3)
  7. * Measurable or evaluable disease
  8. * All lesions should be treatable by EBRT while meeting normal tissue constraints
  9. * Tumor lesions should be accessible using an ultrasound (US)-guided approach for intratumoral DC injection
  10. * No evidence of extrahepatic tumor (excluding tumor thrombus) by computed tomography (CT) or magnetic resonance imaging (MRI) scan
  11. * NOTE: Patients who are not candidates for surgical treatment or for ablation with curative intent are allowed
  12. * Good candidate for standard of care high-dose conformal EBRT in the view of the investigator
  13. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  14. * GROUP 2 HCC ONLY: Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained =\< 15 days prior to registration)
  15. * GROUP 2 HCC ONLY: Absolute lymphocyte count (ALC) \>= 500/mm\^3 (obtained =\< 15 days prior to registration)
  16. * GROUP 2 HCC ONLY: Absolute monocyte count (AMC) \>= 300/mm\^3 (obtained =\< 15 days prior to registration)
  17. * GROUP 2 HCC ONLY: Platelet count \>= 50,000/mm\^3 (obtained =\< 15 days prior to registration)
  18. * GROUP 2 HCC ONLY: Hemoglobin \>= 9.0 g/dL (obtained =\< 15 days prior to registration)
  19. * GROUP 2 HCC ONLY: Total bilirubin \< 1.5 mg/dL (obtained =\< 15 days prior to registration)
  20. * GROUP 2 HCC ONLY: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 5 x upper limit of normal (ULN) (obtained =\< 15 days prior to registration)
  21. * GROUP 2 HCC ONLY: Creatinine =\< 2 mg/dL (obtained =\< 15 days prior to registration)
  22. * GROUP 2 HCC ONLY: Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (obtained =\< 15 days prior to registration)
  23. * GROUP 2 HCC ONLY: Absence of proteinuria at screening as demonstrated by one of the following:
  24. * Urine protein/creatinine (UPC) ratio \< 1.0 at screening OR
  25. * Urine dipstick for proteinuria \< 2+ (patients discovered to have \>= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate =\<1g of protein in 24 hours to be eligible)
  26. * GROUP 3 iCCA ONLY: Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (obtained =\< 15 days prior to registration)
  27. * GROUP 3 iCCA ONLY: Absolute lymphocyte count ≥ 500/mm\^3 (obtained =\< 15 days prior to registration)
  28. * GROUP 3 iCCA ONLY: Absolute monocyte count ≥ 300/mm\^3 (obtained =\< 15 days prior to registration)
  29. * GROUP 3 iCCA ONLY: Platelet count ≥ 100,000/mm\^3 (obtained =\< 15 days prior to registration)
  30. * GROUP 3 iCCA ONLY: Hemoglobin ≥ 9.0 g/dL (obtained =\< 15 days prior to registration)
  31. * GROUP 3 iCCA ONLY: Total bilirubin \< 1.5 x ULN (obtained =\< 15 days prior to registration)
  32. * GROUP 3 iCCA ONLY: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and alkaline phosphatase (ALP) ≤ 2.5 x ULN (obtained =\< 15 days prior to registration)
  33. * GROUP 3 iCCA ONLY: Creatinine ≤ 2 mg/dL (obtained =\< 15 days prior to registration)
  34. * GROUP 3 iCCA ONLY: Serum albumin ≥ 25 g/L (2.5 g/dL) (obtained =\< 15 days prior to registration)
  35. * GROUP 3 iCCA ONLY: PT/INR/aPTT ≤ 1.5 x ULN (obtained =\< 15 days prior to registration)
  36. * NOTE: If patient is receiving therapeutic anticoagulation, patient must be on a stable anticoagulant regimen
  37. * GROUP 3 iCCA ONLY: Calcium ≤ 12 mg/dl or corrected serum calcium ≤ ULN (obtained =\< 15 days prior to registration)
  38. * Negative pregnancy test done =\< 8 days prior to registration, for persons of childbearing potential only
  39. * GROUP 3 ONLY: Negative hepatitis B surface antigen (HBsAg) test at screening
  40. * GROUP 3 ONLY: Negative hepatitis C virus antibody (HCV Ab) test at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening. (NOTE: HCV RNA test will be performed only for patients who have a positive HCV antibody test.)
  41. * Ability to provide written consent
  42. * Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  43. * Willingness to provide blood and tissue samples for correlative research purposes
  1. * Any of the following because this study involves an investigational agent, the genotoxic, mutagenic and teratogenic effects of which on the developing fetus and newborn are unknown:
  2. * Pregnant persons
  3. * Nursing persons
  4. * Persons of childbearing potential who are unwilling to employ highly effective contraception during heterosexual intercourse while on this study and for 5 months after the last dose of study medication
  5. * 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
  6. * Immunocompromised patients and patients known to be HIV positive.
  7. * NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial if they are stable on anti-retroviral therapy, have a CD4+ T cell count ≥ 200/uL, and have an undetectable viral load
  8. * Uncontrolled intercurrent illness including, but not limited to:
  9. * Ongoing or active infection requiring systemic treatment or that could impact patient safety
  10. * Severe infection ≤ 4 weeks prior to registration, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  11. * Significant cardiovascular disease (New York Heart Association \[NYHA\] class II), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
  12. * Or, psychiatric illness/social situations (e.g., substance abuse) that would limit compliance with study requirements
  13. * Receiving any other investigational agent that would be considered a treatment for the primary neoplasm
  14. * Other active malignancy =\< 1 year prior to registration that is considered by the investigator to interfere with the current treatment or measurement of outcomes
  15. * Major surgery =\< 4 weeks prior to enrollment (other than diagnostic surgery or surgical spacer placement in preparation for radiation treatment), or anticipation of need for a major surgical procedure during the study
  16. * History of hypersensitivity or anaphylactoid reactions to pneumococcal vaccine or any component of the formulation, including diphtheria toxoid
  17. * Active or history of autoimmune disease or immune deficiency, including but not limited to,myasthenia gravis, myositis, autoimmune hepatitis, Crohn's disease, inflammatory bowel disease, antiphospholipid antibody syndrome, rheumatoid arthritis, Sjogren syndrome, systemic lupus erythematosus, Guillain-Barre syndrome, multiple sclerosis, Wegener granulomatosis, or similar conditions
  18. * NOTE: Exceptions are allowed for:
  19. * Patients with hypothyroidism on thyroid replacement therapy
  20. * Patients with type 1 diabetes mellitus on insulin regimen
  21. * Patients with eczema, psoriasis lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of the following conditions are met:
  22. * Rash must cover \< 10% of body surface area
  23. * Disease is well controlled at baseline and requires only low-potency topical corticosteroids
  24. * There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids ≤ 12 months prior to registration
  25. * Requires anticoagulant treatment (INR \> 1.5 x ULN) or use of anti-platelet agents that cannot be discontinued for the intratumoral injection procedure
  26. * NOTE: Heparin for line patency without detectable lab abnormalities in coagulation will be allowed
  27. * Corticosteroids =\< 2 weeks prior to registration, including oral, intravenous (IV), subcutaneous, or inhaled routes of administration
  28. * 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)
  29. * NOTE: Exception allowed for patients who need prophylactic steroids prior to imaging for contrast allergies
  30. * Exception: Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study
  31. * Exception: Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study
  32. * History of myocardial infarction =\< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  33. * Child Pugh class B or C cirrhosis of the liver
  34. * 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
  35. * Prior liver radiation, including radioembolization
  36. * GROUP 2 ONLY: Barcelona Clinic Liver Cancer (BCLC) stage D disease
  37. * GROUP 2 ONLY: History of untreated high-risk gastroesophageal varices
  38. * GROUP 3 ONLY: History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
  39. * Active tuberculosis
  40. * Treatment with therapeutic oral or IV antibiotics ≤ 2 weeks prior to registration
  41. * NOTE: Exception for patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study
  42. * Prior allogeneic stem cell or solid organ transplantation
  43. * Treatment with a live, attenuated vaccine ≤ 4 weeks prior to registration, or anticipation of need for such a vaccine during study treatment, within 90 days after the final dose of tiragolumab, or within 5 months after the final dose of atezolizumab
  44. * NOTE: Patients being treated with chemotherapy (e.g., carboplatin, cisplatin, pemetrexed, paclitaxel, or gemcitabine) should not receive live vaccines
  45. * GROUP 3 ONLY: Acute Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV at screening
  46. * NOTE: Patients with symptoms such as splenomegaly, fever, sore throat, non-malignant cervical lymphadenopathy, and/or tonsillar exudate, should undergo an EBV polymerase chain reaction (PCR) test to screen for acute infection or suspected chronic active infection. Patients with a positive EBV PCR test are excluded. Patients with positive Epstein-Barr virus (EBV) viral capsid antigen immunoglobulin M (IgM) test at screening are excluded
  47. * GROUP 3 ONLY: History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
  48. * GROUP 3 ONLY: Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation
  49. * GROUP 3 ONLY: Known allergy or hypersensitivity to any component of the chemotherapy regimen the patient may receive during the study

Contacts and Locations

Study Contact

Clinical Trials Referral Office
CONTACT
855-776-0015
mayocliniccancerstudies@mayo.edu

Principal Investigator

Lewis R. Roberts, MD, PhD
PRINCIPAL_INVESTIGATOR
Mayo Clinic in Rochester

Study Locations (Sites)

Mayo Clinic in Rochester
Rochester, Minnesota, 55905
United States

Collaborators and Investigators

Sponsor: Mayo Clinic

  • Lewis R. Roberts, MD, PhD, PRINCIPAL_INVESTIGATOR, Mayo Clinic in Rochester

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-09-19
Study Completion Date2028-02-29

Study Record Updates

Study Start Date2019-09-19
Study Completion Date2028-02-29

Terms related to this study

Additional Relevant MeSH Terms

  • Stage III Hepatocellular Carcinoma AJCC v8
  • Stage III Intrahepatic Cholangiocarcinoma AJCC v8
  • Stage IV Hepatocellular Carcinoma AJCC v8
  • Stage IV Intrahepatic Cholangiocarcinoma AJCC v8
  • Unresectable Hepatocellular Carcinoma
  • Unresectable Intrahepatic Cholangiocarcinoma