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New treatment option for Stage III Hepatocellular Carcinoma AJCC v8
Official title 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
ClinicalTrials.gov ID: NCT03942328
What this study is testing
What is Atezolizumab?
Atezolizumab is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for stage iii hepatocellular carcinoma ajcc v8.
Also referred to as MPDL 3280A, MPDL 328OA.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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 druvalumab) 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.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Age \>= 18 years
- Pilot study (group 1): Histologic confirmation of intrahepatic CCA (Closed as of amendment 3)
- Phase II study (group 2): Histologic and/or radiologic confirmation of hepatocellular carcinoma (HCC)
- Phase II study (group 3): Histologic confirmation of intrahepatic cholangiocarcinoma (iCCA)
- The following tumor characteristics must be met
You likely can't join if
- Any of the following because this study involves an investigational agent, the genotoxic, mutagenic and teratogenic effects of which on the...
- Pregnant persons
- Nursing persons
- Persons of childbearing potential who are unwilling to employ highly effective contraception during heterosexual intercourse while on this study and...
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for...
- Immunocompromised patients and patients known to be HIV positive.
See the full eligibility criteria
Who can join
- Age \>= 18 years
- Pilot study (group 1): Histologic confirmation of intrahepatic CCA (Closed as of amendment 3)
- Phase II study (group 2): Histologic and/or radiologic confirmation of hepatocellular carcinoma (HCC)
- Phase II study (group 3): Histologic confirmation of intrahepatic cholangiocarcinoma (iCCA)
- The following tumor characteristics must be met
- Unresectable disease: HCC (group 2) or intrahepatic CCA (group 3)
- 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
- 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
- GROUP 2 HCC ONLY: Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained =\< 15 days prior to registration)
- GROUP 2 HCC ONLY: Absolute lymphocyte count (ALC) \>= 500/mm\^3 (obtained =\< 15 days prior to registration)
- GROUP 2 HCC ONLY: Absolute monocyte count (AMC) \>= 300/mm\^3 (obtained =\< 15 days prior to registration)
- GROUP 2 HCC ONLY: Platelet count \>= 50,000/mm\^3 (obtained =\< 15 days prior to registration)
- GROUP 2 HCC ONLY: Hemoglobin \>= 9.0 g/dL (obtained =\< 15 days prior to registration)
- GROUP 2 HCC ONLY: Total bilirubin \< 1.5 mg/dL (obtained =\< 15 days prior to registration)
- GROUP 2 HCC ONLY: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 5 x upper limit of normal (ULN) (obtained =\< 15 days prior to registration)
- GROUP 2 HCC ONLY: Creatinine =\< 2 mg/dL (obtained =\< 15 days prior to registration)
- 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)
- GROUP 2 HCC ONLY: Absence of proteinuria at screening as demonstrated by one of the following:
- Urine protein/creatinine (UPC) ratio \< 1.0 at screening OR
- Urine dipstick for proteinuria \ = 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)
- GROUP 3 iCCA ONLY: Absolute neutrophil count (ANC) ≥ 1000/mm\^3 (obtained =\< 15 days prior to registration)
- GROUP 3 iCCA ONLY: Absolute lymphocyte count ≥ 500/mm\^3 (obtained =\< 15 days prior to registration)
- GROUP 3 iCCA ONLY: Absolute monocyte count ≥ 300/mm\^3 (obtained =\< 15 days prior to registration)
- GROUP 3 iCCA ONLY: Platelet count ≥ 50,000/mm\^3 (obtained =\< 15 days prior to registration)
- GROUP 3 iCCA ONLY: Hemoglobin ≥ 9.0 g/dL (obtained =\< 15 days prior to registration)
- GROUP 3 iCCA ONLY: Total bilirubin \< 1.5 x ULN (obtained =\< 15 days prior to registration)
- 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)
- GROUP 3 iCCA ONLY: Creatinine ≤ 2 mg/dL (obtained =\< 15 days prior to registration)
- GROUP 3 iCCA ONLY: PT/INR/aPTT ≤ 1.5 x ULN (obtained =\< 15 days prior to registration)
- NOTE: If patient is receiving therapeutic anticoagulation, patient must be on a stable anticoagulant regimen
- 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
What rules you out
- 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:
- Pregnant persons
- Nursing persons
- 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
- 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...
- Immunocompromised patients and patients known to be HIV positive.
- 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...
- Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection requiring systemic treatment or that could impact patient safety
- Severe infection ≤ 4 weeks prior to registration, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- Significant cardiovascular disease (New York Heart Association [NYHA] class II), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
- Or, psychiatric illness/social situations (e.g., substance abuse) 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 =\< 1 year prior to registration that is considered by the investigator to interfere with the current treatment or measurement of outcomes
- 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
- History of hypersensitivity or anaphylactoid reactions to pneumococcal vaccine or any component of the formulation, including diphtheria toxoid
- 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...
- NOTE: Exceptions are allowed for:
- Patients with hypothyroidism on thyroid replacement therapy
- Patients with type 1 diabetes mellitus on insulin regimen
- 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...
- Rash must cover \< 10% of body surface area
- Disease is well controlled at baseline and requires only low-potency topical corticosteroids
- 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...
- Requires anticoagulant treatment (INR \> 1.5 x ULN) 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)
- NOTE: Exception allowed for patients who need prophylactic steroids prior to imaging for contrast allergies
- 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...
- 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...
- 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
- GROUP 2 ONLY: Barcelona Clinic Liver Cancer (BCLC) stage D disease
- GROUP 2 ONLY: History of untreated high-risk gastroesophageal varices
- Active tuberculosis
- Treatment with therapeutic oral or IV antibiotics ≤ 2 weeks prior to registration
- 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
- Prior allogeneic stem cell or solid organ transplantation
- Treatment with a live, attenuated vaccine ≤ 4 weeks prior to registration
The study team makes the final eligibility decision.
Where it's taking place
- Rochester, Minnesota, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Rochester, Minnesota, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.