Durvalumab and Tremelimumab After Radioembolization for the Treatment of Unresectable Locally Advanced Liver Cancer

  • STATUS
    Recruiting
  • End date
    Dec 31, 2023
  • participants needed
    32
  • sponsor
    City of Hope Medical Center
Updated on 20 August 2021

Summary

This phase Ib trial investigates the side effects of durvalumab and tremelimumab after radioembolization (radiation particles against liver tumors) and to see how well they work in treating patients with liver cancer that cannot be removed by surgery (unresectable) and has spread to nearby tissues and lymph nodes (locally advanced). Durvalumab and tremelimumab are antibodies (proteins produced by the defense system of the body [immune system]) that have been made in the laboratory and may improve the ability of the immune system to detect and fight cancer.

Description

PRIMARY OBJECTIVES:

I. To establish the safety of durvalumab and tremelimumab following radioembolization with Yttrium-90 selective internal radiation (SIR)-spheres in patients with locally advanced hepatocellular carcinoma without extra-hepatic disease.

II. If the combination of durvalumab and tremelimumab is deemed unsafe, to establish the safety of single agent durvalumab and explore all endpoints with durvalumab alone.

III. To evaluate the overall response rate in patients treated with durvalumab and tremelimumab following radioembolization with Yttrium-90 SIR-Spheres using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, modified (m) RECIST and immune modified RECIST criteria.

SECONDARY OBJECTIVES:

I. To evaluate the rate of 6-month progression-free survival in patients treated with durvalumab and tremelimumab following radioembolization with Yttrium-90 SIR-spheres.

II. To evaluate median progression-free survival and overall survival in patients treated with durvalumab and tremelimumab following radioembolization with Yttrium-90 SIR-spheres.

EXPLORATORY OBJECTIVES:

I. To explore the association of response and survival outcomes with PD-L1 expression of baseline tumor biopsies.

II. To explore the association of response and survival outcomes with next generation sequencing results including tumor mutational burden of baseline tumor biopsies.

III. To explore genomic alterations/evolutions in tumor tissue following Yttrium-90 SIR-spheres and durvalumab plus tremelimumab through comparison of baseline and post-combination immunotherapy treatment tumor biopsies.

IV. To explore the association of response and survival outcomes with gene expression signatures.

OUTLINE

Patients undergo standard of care radioembolization with Yttrium-90 SIR-spheres intra-arterially over 60-90 minutes on day -14. Patients then receive durvalumab intravenously (IV) over 1 hour and tremelimumab IV over 1 hour on day 1. Cycles with durvalumab repeat every 4 weeks for 12 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 90 days, and then every 12 weeks thereafter.

Details
Condition Stage III Hepatocellular Carcinoma AJCC v8, BCLC Stage C Hepatocellular Carcinoma, BCLC Stage B Hepatocellular Carcinoma, Locally Advanced Hepatocellular Carcinoma, Stage IIIA Hepatocellular Carcinoma AJCC v8, Stage IVA Hepatocellular Carcinoma AJCC v8, Stage IVB Hepatocellular Carcinoma AJCC v8, Unresectable Hepatocellular Carcinoma, Stage IIIB Hepatocellular Carcinoma AJCC v8, Stage IV Hepatocellular Carcinoma AJCC v8
Treatment tremelimumab, durvalumab
Clinical Study IdentifierNCT04605731
SponsorCity of Hope Medical Center
Last Modified on20 August 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician
Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab and/or tremelimumab may be included only after consultation with the study physician
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this
criterion
Patients with vitiligo or alopecia
Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
Any chronic skin condition that does not require systemic therapy
Patients without active disease in the last 5 years may be included but only after consultation with the study physician
Patients with celiac disease controlled by diet alone
History of allogenic organ transplantation
Evidence of pulmonary lung shunt greater than 10% or expected lung dose of > 30 Gy
Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the patient to give written informed consent
History of another primary malignancy except for
Malignancy treated with curative intent and with no known active disease >= 5 years before the first dose of study treatment and of low potential risk for recurrence
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
Adequately treated carcinoma in situ without evidence of disease
History of active primary immunodeficiency
Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment
Note: Patients, if enrolled, should not receive live vaccine whilst receiving study treatment and up to 30 days after the last dose of study treatment
Active systemic infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis (TB) testing in line with local practice. Use of antibiotics to treat superficial infection or contamination of tumor shall not, by itself, be considered evidence of infection
History of leptomeningeal carcinomatosis
Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion
Intranasal, inhaled, topical steroid or local steroid injections (e.g., intra articular injection)
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication)
Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is longer
Female subjects, unless postmenopausal or surgically sterile, unwillingness to practice effective contraception, as per investigator discretion during the study. The rhythm method is not to be used as the sole method of contraception
Male subjects, unwillingness to practice effective contraception (per investigator discretion) while taking part in this study, because the effects of the SIR-Spheres treatment on sperm or upon the development of an unborn child are unknown
Inability or unwillingness to understand or sign a written informed consent document
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Exclusion Criteria

Portal vein invasion at the main portal branch (Vp4), inferior vena cava, or cardiac involvement of hepatocellular carcinoma (HCC) based on imaging. Vascular invasion to portal vein side branches are eligible for study
Evidence of diffuse HCC (tumor burden occupying > 50% of liver)
Any evidence of known metastatic disease
Major surgical procedure (as defined by the investigator) within 28 days prior to radioembolization
Note: Local surgery of isolated lesions for palliative intent is acceptable
Participation in another clinical study with an investigational product during the last 4 weeks
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) =< 28 days prior to the first dose of study drug. If sufficient wash-out time has not occurred due to the schedule or pharmacokinetic (PK) properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca/MedImmune and the investigator
Prior exposure to anti-PD-1/PD-L1 inhibitor or anti-CTLA4 inhibitor, including durvalumab or tremelimumab
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note