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Durvalumab With/Without Tremelimumab After Palliative Hypofractionated Radiotherapy for Hepatocellular Carcinoma

ConditionsAdvanced Hepatocellular CarcinomaStage III Hepatocellular Carcinoma AJCC v8Stage IIIA Hepatocellular Carcinoma AJCC v8Stage IIIB Hepatocellular Carcinoma AJCC v8Stage IV Hepatocellular Carcinoma AJCC v8Stage IVA Hepatocellular Carcinoma AJCC v8Stage IVB Hepatocellular Carcinoma AJCC v8
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMary Feng, MD

About this trial

This phase II trial studies how well standard of care hypofractionated radiation therapy followed by durvalumab with or without tremelimumab works in treating patients with hepatocellular cancer (liver cancer) that has spread to other places in the body (advanced) and that is growing, spreading, or getting worse (progressing). In some patients, cancer cells and immune cells start to express signals that stop the body's immune system from killing the cancer. New drugs being developed, such as durvalumab and tremelimumab, are designed to target and block these signals and may help increase the immune response to prevent or slow down cancer growth. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may help the immune system work even better. Giving durvalumab with or without tremelimumab after radiation therapy may work better than radiation therapy alone in treating patients with liver cancer.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Histologically-diagnosed HCC with progression during or after prior PD-(L)1 checkpoint inhibitor immunotherapy (e.g., nivolumab and/or pembrolizumab or atezolizumab; prior durvalumab excluded), or without prior PD-(L)1 checkpoint inhibitor immunotherapy.

At least 1 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1-measurable tumor present which has not received RT or other local therapy prior to enrollment.

Clinical indication for RT to any site (e.g. painful primary or metastatic tumor, local complication risk such as impending biliary or vascular obstruction).

Child Pugh score of A, B7, or B8 provided other liver function criteria are met.

Disqualifiers

Prior radiotherapy to tumor sites requiring RT which could compromise safety of additional treatments.

Prior radiotherapy to more than 30% of bone marrow or to a wide field within 4 weeks of the first study treatment.

Prior treatment with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or PD-L1 inhibitor.

History of allogenic organ transplantation.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Durvalumab

    Biological/Vaccine

    Given IV

  • Hypofractionated Radiation Therapy

    Radiation

    Undergo hypofractionated RT

  • Tremelimumab

    Biological/Vaccine

    Given IV

Treatment groups

21 Participants
are divided into 3 treatment groups
Group A: Arm I: Durvalumab monotherapy + hypofractionated radiotherapy (RT)Experimental treatment 2 interventions
Group B: Arm II: Progression on prior programmed death-ligand 1 (PD-L1) checkpoint inhibitorsExperimental treatment 3 interventions
Group C: Arm III: No previous PD-L1 checkpoint inhibitor therapyExperimental treatment 0 interventions

Trial outcomes

Primary outcomes

1

Objective response rate (ORR)

Response is defined per Response Evaluation Criteria in Solid Tumors 1.1 as a complete response (CR) or Partial Response (PR) (CR+PR=ORR) excluding radiation therapy-treated lesions. Response will be assessed after participants complete 5 fractions of standard palliative radiotherapy (RT). Proportion of participants with a confirmed response and corresponding exact confidence intervals will be reported by Arm. Participants with unevaluable or unknown response status will be considered non-responders

Time frame
Up to 2 years

Secondary outcomes

1

Proportion of participants with reported treatment-related adverse events

The proportion of participants with reported adverse events that are determined to be definitely, possibly, or probably related to the study treatment will be reported by arm

Time frame
Up to 2 years
2

Median Duration of overall response (DOR)

The period measured from the time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the first date that recurrent or progressive disease is objectively documented, taking as reference the smallest measurements recorded since treatment started

Time frame
Up to 2 years
3

Median Duration of overall Complete Response (DOCR)

The period measured from the time that measurement criteria are met for complete response (whichever status is recorded first) until the first date that recurrent or progressive disease is objectively documented, taking as reference the smallest measurements recorded since treatment started

Time frame
Up to 2 years
4

Median Duration of overall Complete Response (DOSD)

measurement from first dose of protocol therapy until the criteria for disease progression is met, taking as reference the smallest measurements recorded since registration. To be assigned a status of stable disease, measurements must have met the stable disease criteria at least once after study entry at a minimum interval of not less than six weeks

Time frame
Up to 2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Mary Feng, MD

Lead sponsor

University of California, San Francisco

Sponsor institution

AstraZeneca

Collaborator

Source ClinicalTrials.gov
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