Recruiting
Phase 2

Drug Combination

Sponsor:

Canadian Cancer Trials Group

Code:

NCT06880523

Conditions

Hepatocellular Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

STRIDE (durvalumab + tremelimumab)

Durvalumab

Lenvatinib

Study Details

Brief summary:

The purpose of this study is to compare the effects on participants' and liver cancer by adding a drug that is used on its own to treat this disease to a combination of two other drugs which is also used to treat liver cancer, compared to the two-drug combination alone.

Conditions

Hepatocellular Carcinoma

Study ID

NCT06880523

Start date

Oct 21, 2025

Status verified date

Oct, 2025

Completion date

Dec 31, 2028

Anticipated

Primary completion date

Jan 31, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Age ≥ 18 years.
  • Body weight > 30 kg.
  • Life expectancy of at least 12 weeks.
  • Confirmed HCC based on histopathological findings from tumour tissues or clinically by AASLD criteria in cirrhotic participants.
  • Must not have received prior systemic therapy for HCC.
  • Must not be eligible for locoregional therapy for unresectable HCC. For patients who progressed after locoregional therapy for HCC, locoregional therapy must have been completed ≥28 days prior to the baseline scan of the abdomen and pelvis for the current study.
  • Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C.
  • Child-Pugh Score class A or B7 based on low albumin (albumin 25-27 g/L) only.
  • Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • At least 1 measurable lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis ≥15 mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines. A lesion which progressed after previous ablation or TACE could be measurable if it meets these criteria.
  • Participants with active HBV infection \[characterized by positive hepatitis B virus surface antigen (HBsAg) and/or positive hepatitis B core antibodies (anti-HBcAb) with detectable HBV deoxyribonucleic acid (DNA) (≥10 IU/mL or above the limit of detection per local lab standard)\] are eligible if:
  • The participant is being treated with antiviral therapy, as per institutional practice. The HBV antiviral therapy must be initiated prior to randomization, and the participant must remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication.
  • The participant must show evidence of HBV stabilization or signs of viral response (eg, reduction of HBV DNA levels) prior to enrollment
  • Participants who test positive for HBsAg or anti-hepatitis B core (HBc) with undetectable HBV DNA (< 10 IU/mL or under the limit of detection per local lab standard) are eligible and do not require antiviral therapy prior to randomization.
  • These participants will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥ 10 IU/mL or above the limit of detection per local lab standard).
  • If HBV DNA becomes detectable during study treatment, antiviral therapy must be initiated, and the participant must remain on antiviral therapy during the study treatment period and for 6 months after the last dose of study medication.
  • Participants with active HCV infection (as characterized by the presence of detectable HCV ribonucleic acid \[RNA\] or anti-HCV antibody \[anti-HCV\]) must be managed per local institutional practice for the study and for 6 months after the last dose of study treatment.
  • Adequate organ and marrow function, within 14 days prior to enrollment.
  • Participants of childbearing potential must have agreed to use a highly effective contraceptive method from enrollment to 90 days after the last dose of durvalumab or 180 days after the last dose of tremelimumab (whichever date is later).
  • Participants must agree not to donate blood for at least 90 days following the last infusion of durvalumab or tremelimumab, or until 7 days after the last dose of lenvatinib, whichever is longest.

Exclusion Criteria:

  • Participants with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other tumours curatively treated with no evidence of disease for ≥ 5 years.
  • Any concurrent chemotherapy, study drug, or biologic or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
  • Known fibrolamellar HCC, sarcomatoid HCC, infiltrative-type HCC or mixed cholangiocarcinoma and HCC.
  • Clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention
  • Uncontrolled arterial hypertension defined by a systolic pressure ≥ 150 mm Hg or diastolic pressure ≥ 90 mm Hg or other hypertensive cardiovascular complications despite standard medical management.
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab, or an anti-CTLA4, including tremelimumab.
  • History of primary immunodeficiency, history of organ transplant or prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy.
  • Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab
  • Active or prior documented autoimmune or inflammatory disorders including inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis), diverticulitis (with the exception of diverticulosis), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.
  • Patients with active or uncontrolled intercurrent illness
  • History of leptomeningeal carcinomatosis.
  • Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to enrollment.
  • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart).
  • Receipt of live attenuated vaccination (examples include, but are not limited to, vaccines for measles, mumps, and rubella, live attenuated influenza vaccine (nasal), chicken pox vaccine, oral polio vaccine, rotavirus vaccine, yellow fever vaccine, BCG vaccine, typhoid vaccine and typhus vaccine) within 30 days prior to enrollment.
  • Lactating participants.
  • Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
  • Receipt of radiotherapy within four weeks of first planned dose of durvalumab or tremelimumab, except for a single dose of radiation up to 8 Gray (equal to 800 RAD) delivered with palliative intent for pain control up to 14 days before enrollment.
  • Active or prior documented GI bleeding (e.g. esophageal varices or ulcer bleeding) within 6 months. (Note: For patients with a history of GI bleeding more than 6 months prior or assessed as high risk for esophageal varices by the Investigator or main trunk portal vein thrombosis (Vp4), adequate endoscopic assessment and treatment of varices as per institutional standards is required prior to enrollment.)

Study Design

Enrollment

140 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: STRIDE (durvalumab + tremelimumab)

experimental: STRIDE (durvalumab + tremelimumab) + Lenvatinib

Interventions

STRIDE (durvalumab + tremelimumab)

As first treatment

Durvalumab

monotherapy every 4 weeks

Lenvatinib

Daily

Primary outcome measure

  • Progression-free Survival using RECIST 1.1 [ Time Frame: 32 months ]

Central Contacts and Locations

Central contacts

Chris O'Callaghan

613-533-6430cocallaghan@ctg.queensu.ca

Locations

Arthur J.E. Child Comprehensive Cancer Centre

Recruiting

Calgary, Alberta, Canada, T2N 5G2

Contacts

Vincent Tam

403 521-3706

BCCA - Kelowna

Recruiting

Kelowna, British Columbia, Canada, V1Y 5L3

Contacts

David Nguyen

250 712-3900

BCCA - Vancouver

Recruiting

Vancouver, British Columbia, Canada, V5Z 4E6

Contacts

Howard Lim

604 877-6000

Juravinski Cancer Centre at Hamilton Health Sciences

Recruiting

Hamilton, Ontario, Canada, L8V 5C2

Kingston Health Sciences Centre

Recruiting

Kingston, Ontario, Canada, K7L 2V7

Waterloo Regional Health Network (WRHN)

Recruiting

Kitchener, Ontario, Canada, N2G 1G3

London Health Sciences Centre Research Inc.

Recruiting

London, Ontario, Canada, N6A 5W9

Contacts

Elena Tsvetkova

519 685-8500

Trillium Health Partners - Credit Valley Hospital

Recruiting

Mississauga, Ontario, Canada, L5M 2N1

Contacts

Mala Bahl

416 521-4118

Ottawa Hospital Research Institute

Recruiting

Ottawa, Ontario, Canada, K1H 8L6

Contacts

Dominick Bosse

613 737-7700

University Health Network

Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contacts

Jennifer Knox

416 946-2399

CHUM-Centre Hospitalier de l'Universite de Montreal

Recruiting

Montreal, Quebec, Canada, H2X 3E4

Contacts

Helene Castel

514 890-8000

The Jewish General Hospital

Recruiting

Montreal, Quebec, Canada, H3T 1E2

Contacts

Petr Kavan

514 398-1444

Saskatoon Cancer Centre

Recruiting

Saskatoon, Saskatchewan, Canada, S7N 4H4

Contacts

Osama Ahmed

306 655-2662

More Information

Sponsor

Canadian Cancer Trials Group

Last update posted

Aug 11, 2026

Last verified

Oct, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Canadian Cancer Trials Group on 2026-08-11.