SELINEXOR in Combination w/Bevacizumab and Atezolizumab in Newly Diagnosed Advanced Hepatocellular Carcinoma

NCT05093608 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: MCC-21178KPT-IST-334
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find out if the oral drug Selinexor taken along with bevacizumab and atezolizumab is effective in treating advanced Hepatocellular Carcinoma.

Conditions

Hepatocellular Carcinoma

Keywords

liver cancer

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  Maximum Tolerated Dose (MTD) of Selinexor when combined with Bevacizumab and Atezolizumab will be determined by testing 2 dose levels. MTD reflects that highest dose that did not cause Dose Limiting Toxicity (DLT)

  Up to 24 months

Secondary Outcomes (4)

• Rate of Objective Response (per RECIST)

  Up to 24 months

• Rate of Objective Response (per mRECIST)

  Up to 24 months

• Progression Free Survival

  Up to 24 months

• Overall Survival

  up to 24 months

Study Arms (2)

Dose Level 1 - 60 mg Selinexor with Bevacizumab and Atezolizumab

EXPERIMENTAL

60 mg Selinexor (oral tablet) will be administered once a week continuously. Bevacizumab and atezolizumab will be administered intravenously once every 3 weeks. Each cycle length will be 21 days. On the days when Selinexor and bevacizumab/atezolizumab are given the same day, Selinexor will be administered prior to the intravenous infusions of bevacizumab and atezolizumab.

Drug: Selinexor Pill; Drug: Bevacizumab; Drug: Atezolizumab

Dose Level 2 - 80 mg Selinexor with Bevacizumab and Atezolizumab

EXPERIMENTAL

80 mg Selinexor (oral tablet) will be administered once a week continuously. Bevacizumab and atezolizumab will be administered intravenously once every 3 weeks. Each cycle length will be 21 days. On the days when Selinexor and bevacizumab/atezolizumab are given the same day, Selinexor will be administered prior to the intravenous infusions of bevacizumab and atezolizumab.

Drug: Selinexor Pill; Drug: Bevacizumab; Drug: Atezolizumab

Interventions

Selinexor Pill DRUG

Selinexor 60 mg or 80 mg (oral table) will be administered once a week.

Also known as: Xpovio

Dose Level 1 - 60 mg Selinexor with Bevacizumab and Atezolizumab; Dose Level 2 - 80 mg Selinexor with Bevacizumab and Atezolizumab

Bevacizumab DRUG

Bevacizumab will be administered at a standard dose of 15 mg/kg every 3 weeks.

Also known as: Mvasi

Dose Level 1 - 60 mg Selinexor with Bevacizumab and Atezolizumab; Dose Level 2 - 80 mg Selinexor with Bevacizumab and Atezolizumab

Atezolizumab DRUG

Atezolizumab will be administered intravenously a standard dose of 12,000 mg every 3 weeks.

Also known as: Tecentriq

Dose Level 1 - 60 mg Selinexor with Bevacizumab and Atezolizumab; Dose Level 2 - 80 mg Selinexor with Bevacizumab and Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent in accordance with federal, local, and institutional guidelines. Participants must provide informed consent prior to the first screening procedure.
• Ability to comply with the study protocol, in the investigator's judgment.
• Locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic patients. Participants without cirrhosis require histological confirmation of diagnosis.
• Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and/or locoregional therapies.
• No prior anti-neoplastic systemic therapy (including systemic investigational agents) for HCC
• At least 1 measurable (per RECIST v1.1) untreated lesion.
• Participants who received prior local therapy (e.g., radiofrequency ablation, percutaneous ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound, transarterial chemoembolization, transarterial embolization, etc.) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST version 1.1.
• Participants must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed and treated per local standard of care prior to enrollment. Participants who have undergone an EGD within 6 months of prior to initiation of study treatment do not need to repeat the procedure.
• Eastern Cooperative Oncology Group (ECOG ) Performance Status (PS) of ≤ 2
• Participants with brain metastases must have treated and stable brain metastases.
• Child-Pugh Class A within 7 days prior to Cycle 1 Day 1.
• Adequate hepatic function at screening
• Adequate renal function within 28 days prior to cycle 1 day 1
• Adequate hematopoietic function within 7 days prior to cycle 1 day 1
• Urine dipstick for proteinuria \<2+ (within 28 days of cycle 1 day 1. Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate \< 1 g of protein in 24 hours.

You may not qualify if:

• History of leptomeningeal disease
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain Barré syndrome, or multiple sclerosis, with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• 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 following conditions are met: (a) Rash must cover ≤ 10% of body surface area (b) Disease is well controlled at baseline and requires only low-potency topical corticosteroids (c) 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 within the previous 12 months
• Prior exposure to a SINE compound, including SELINEXOR.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Known active tuberculosis
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment), unstable arrhythmia, or unstable angina
• History of congenital long QT syndrome or corrected QT interval \>500msec (calculated with use of the Fridericia method) at screening
• Prior allogeneic stem cell or solid organ transplantation
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

selinexor; Bevacizumab; atezolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Rutika Mehta, MD, MPH

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2021
• First Posted: October 26, 2021
• Study Start: November 3, 2021
• Primary Completion: October 12, 2022
• Study Completion: October 12, 2022
• Last Updated: October 17, 2022

Record last verified: 2022-10

Locations

US (1)