Hepatocellular CarcinomaPhase 1NCT05093608
SELINEXOR in Combination w/Bevacizumab and Atezolizumab in Newly Diagnosed Advanced Hepatocellular Carcinoma
A Phase 1 study testing Selinexor Pill, Bevacizumab and Atezolizumab in people with Hepatocellular Carcinoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Selinexor Pill, Bevacizumab and Atezolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Nov 2021to 12 Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- No known history of human immunodeficiency virus.
- Documented virology status of hepatitis, as confirmed by screening HBV and HCV serology test. For patients with active hepatitis B virus (HBV): HBV DNA ≤ 500 IU/mL obtained within 28 days prior to initiation of study treatment, and Anti-HBV treatment (per local standard of care, e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study
- Female participants of childbearing potential must agree to use 2 methods of contraception (including 1 highly effective and 1 effective method of contraception) and have a negative serum pregnancy test at Screening. Male participants must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female participants, effective methods of contraception must be used throughout the study and for 6 months following the last dose of study treatment. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.
Who cannot join
- 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.
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- 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
- Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding. A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
- Co-infection of HBV and hepatitis C virus (HCV). Participants with a history of HCV infection but who are negative for HCV RNA by polymerase chain reaction (PCR) will be considered non-infected with HCV.
- Uncontrolled tumor-related pain, symptomatic hypercalcemia (ionized calcium >1.5 mmol/L, calcium >12 mg/dL or corrected serum calcium > ULN); pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures. Participants with indwelling catheters are allowed.
- Treatment with investigational therapy within 28 days prior to initiation of study treatment
- Treatment with strong CYP3A4 inducers within 14 days prior to initiation of study treatment, including rifampin (and its analogues) or St. John's wort
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti PD-1, and anti-PD-L1 therapeutic antibodies
- Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
- Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, an anti-Tumor Necrosis Factor [TNF] -α agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions: If patient is on chronic steroid prednisone equivalent less than 15 mg/day are allowed.
- Inadequately controlled arterial hypertension (defined as systolic blood pressure (BP) ≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg), based on an average of ≥ 3 BP readings on ≥ 2 sessions. Anti hypertensive therapy to achieve these parameters is allowable.
- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to initiation of study treatment
- History of life-threatening bleeding within 3 months of C1D1, bleeding diathesis or significant coagulopathy.
- Current or recent (within 10 days of first dose of study treatment) use of anti-platelet treatment, full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose
- History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months prior to initiation of study treatment
- History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding prior to initiation of study treatment
- Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
- Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses (< 30 mm from the carina) of large volume
- Participants with vascular invasion of the portal or hepatic veins may be enrolled.
- Radiotherapy, local therapy to the liver or major surgical procedure within 28 days of C1D1 of treatment.
- Chronic daily treatment with a nonsteroidal anti-inflammatory drug (NSAID). Occasional use of NSAIDs for the symptomatic relief of medical conditions such as headache or fever is allowed.
- Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Investigator-initiated Phase I Study of SELINEXOR in Combination With Bevacizumab and Atezolizumab in Newly Diagnosed Advanced Hepatocellular Carcinoma
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
- Being tested
- Selinexor Pill, Bevacizumab, Atezolizumab
- Keywords
- liver cancer
- Medical subject headings
- Carcinoma, Hepatocellular, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Selinexor PillDrug
Also called Xpovio
Selinexor 60 mg or 80 mg (oral table) will be administered once a week.
BevacizumabDrug
Also called Mvasi
Bevacizumab will be administered at a standard dose of 15 mg/kg every 3 weeks.
AtezolizumabDrug
Also called Tecentriq
Atezolizumab will be administered intravenously a standard dose of 12,000 mg every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Selinexor Pill; Drug: Bevacizumab; Drug: Atezolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Up to 24 months
Secondary outcomes (4)
Rate of Objective Response (per RECIST)
Objective response is defined as the sum of complete and partial response as determined by Response Evaluation in Solid Tumors (RECIST) guidelines version 1.1
Measured: Up to 24 months
Rate of Objective Response (per mRECIST)
Objective response is defined as the sum of complete and partial response as determined by hepatocellular carcinoma modified RECIST (mRECIST).
Measured: Up to 24 months
Progression Free Survival
Progression Free Survival (PFS) defined as the time from start of treatment to documented disease progression or death due to any cause.
Measured: Up to 24 months
Overall Survival
Overall Survival (OS) defined as the time from first dose of study treatment until death from any cause.
Measured: up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2021
- Study start3 Nov 2021
- Primary completion12 Oct 2022
- Study completion12 Oct 2022
Why it stopped: Loss of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Karyopharm Therapeutics Inc
- Responsible party
- Sponsor
- Investigators
- Rutika Mehta, MD, MPH, Principal investigator, Moffitt Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05093608
- Sponsor's protocol ID
- MCC-21178
- Other IDs
- KPT-IST-334
- Status last verified
- Oct 2022
- First submitted
- 15 Oct 2021
- Last updated
- 17 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigator-initiated Phase I Study of SELINEXOR in Combination With Bevacizumab and Atezolizumab in Newly Diagnosed Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT05093608
- Acronym / sponsor ID
- MCC-21178
- Conditions
- Hepatocellular Carcinoma
- Keywords
- liver cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Loss of funding
- Enrolment
- 2 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Karyopharm Therapeutics Inc
- Study start
- 3 Nov 2021 (actual)
- Primary completion
- 12 Oct 2022 (actual)
- Study completion
- 12 Oct 2022 (actual)
- First posted
- 26 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 - 60 mg Selinexor with Bevacizumab and Atezolizumab | Experimental | Drug: Selinexor Pill, Drug: Bevacizumab, Drug: Atezolizumab60 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. |
| Dose Level 2 - 80 mg Selinexor with Bevacizumab and Atezolizumab | Experimental | Drug: Selinexor Pill, Drug: Bevacizumab, Drug: Atezolizumab80 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (35 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Selinexor PillAlso: XpovioSelinexor 60 mg or 80 mg (oral table) will be administered once a week. | Drug | Dose Level 1 - 60 mg Selinexor with Bevacizumab and Atezolizumab, Dose Level 2 - 80 mg Selinexor with Bevacizumab and Atezolizumab |
| BevacizumabAlso: MvasiBevacizumab will be administered at a standard dose of 15 mg/kg every 3 weeks. | Drug | Dose Level 1 - 60 mg Selinexor with Bevacizumab and Atezolizumab, Dose Level 2 - 80 mg Selinexor with Bevacizumab and Atezolizumab |
| AtezolizumabAlso: TecentriqAtezolizumab will be administered intravenously a standard dose of 12,000 mg every 3 weeks. | Drug | Dose Level 1 - 60 mg Selinexor with Bevacizumab and Atezolizumab, Dose Level 2 - 80 mg Selinexor with Bevacizumab and Atezolizumab |
Primary outcome
Maximum Tolerated Dose
Time frame: Up to 24 months
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)
4 secondary outcomes
Rate of Objective Response (per RECIST)
Time frame: Up to 24 months
Rate of Objective Response (per mRECIST)
Time frame: Up to 24 months
Progression Free Survival
Time frame: Up to 24 months
Overall Survival
Time frame: up to 24 months
Results and safety
The study was stopped early (reason given: Loss of funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rutika Mehta, MD, MPH principal investigator
Moffitt Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Selinexor Pill, Bevacizumab and Atezolizumab in people with Hepatocellular Carcinoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Loss of funding). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2022.