This study is NOT currently recruiting participants.
Number
000826-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Recruitment has not started Gender: Male & Female Min Age: 18 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Children
Keywords
Tki Na(SqrRoot) ve; Novosome 340; Multi-Kinase Inhibitor
Recruitment Keyword(s)
None
Condition(s)
Cirrhosis; Viral Hepatitis; Child-Pugh A Liver Dysfunction
Investigational Drug(s)
sorafenib MTL-CEBPA
Investigational Device(s)
Intervention(s)
Drug: MTL-CEBPA Drug: sorafenib
Supporting Site
National Cancer Institute
Hepatocellular carcinoma (HCC), or liver cancer, is the sixth most common cancer in the world. It is also the third leading cause of cancer death. More than 695,000 people in the world die from HCC each year. Better treatments are needed.
Objective:
To test a study drug (MTL-CEBPA) combined with another drug (sorafenib), as well as sorafenib alone, in people with advanced HCC.
Eligibility:
People aged 18 years or older who have advanced HCC with cirrhosis and a history of hepatitis B and/or C. The cancer must have either not responded to treatment or returned after treatment.
Design:
Participants will be screened. They will have a physical exam, blood tests, and a test of their heart function. They will have a CT scan. They may have an optional biopsy of the tumor.
All participants will take sorafenib. The drug is a tablet taken by mouth. They will take 4 tablets daily: 2 in the morning and 2 in the evening.
Some participants will also receive MTL-CEBPA. This drug is given through a tube attached to a needle inserted into a vein in the arm. They will receive this drug once a week for 3 weeks, followed by a week of rest.
All participants will visit the clinic up to 4 times in each 4-week treatment cycle. They will have blood tests at every visit. They will have a CT scan every 8 weeks while they remain in the study.
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INCLUSION CRITERIA:<TAB> 1. Written informed consent obtained prior to any specific trial-related procedure. 2. Male or female 18 years or older. 3. Histologically confirmed advanced HCC with cirrhosis in a participant with a history of hepatitis B and/or C. Participants with past or ongoing HCV infection will be eligible for the study. Participants must have completed their treatment at least 1 month prior to starting study intervention and their HCV viral load below the limit of quantification. Participants who are HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution will be eligible. Participants with past or controlled ongoing hepatitis B will be eligible as long as their HBV viral load is less than 500 IU/mL prior to first dose of study drug. Participants on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study intervention. 4. Child-Pugh classification A. 5. Unsuitable for liver tumour resection and/or refractory to loco-regional therapy. 6. Not eligible for liver transplantation. 7. Had progression or recurrence of HCC following previous treatment with atezolizumab in combination with bevacizumab. 8. Naive to tyrosine kinase inhibitors, including sorafenib, regorafenib, cabozantinib, and lenvatinib. 9. Participants with BCLC stage C disease. BCLC Stage B will be allowed if not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach. 10. Eastern Cooperative Oncology Group performance status of 0 or 1. 11. Has the ability to swallow and retain oral medication. 12. At least one measurable liver lesion (RECIST v1.1) assessed by the investigator. 13. Platelet count >70 x10^9/L. 14 Serum albumin >=28g/L. 15. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=5 x the upper limit of normal (ULN). 16. Bilirubin <=50 Micromol /L. 17. White Blood Cell (WBC) >=2.0 x 10^9/L. 18. Absolute neutrophil count >=1.5 x 10^9/L. 19. Haemoglobin >=9.0 g/dL. 20. International Normalized Ratio (INR) <1.5. 21. Calculated creatinine clearance >=50 mL/min (Cockcroft & Gault). 22. AEs due to prior therapy must have resolved to Grade <=1 (except alopecia or endocrinopathies that are adequately managed through hormone replacement treatment). 23. Negative blood pregnancy test for women of childbearing potential (within 10 days prior to first drug administration). Note: a woman is considered of child-bearing potential following menarche and until becoming post-menopausal unless permanently sterile. Permanent methods of sterilisation include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A post-menopausal state is defined as no menses for 12 months without an alternative medical cause. 24. Female participants of childbearing potential must use highly effective* contraceptive measures adequate to prevent a new pregnancy for the duration of the study treatment with MTL-CEBPA and sorafenib and, in addition, for at least six months after the last dose of MTL-CEBPA and six months beyond the last dose of sorafenib, as recommended in sorafenib s U.S. Package Insert (USPI). For women with reproductive potential who use a hormonal method of contraception, concurrent use of a second (barrier) method is recommended. * Highly effective methods of birth control are defined as those that result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly (e.g. implants, injectables, oral contraceptives, some intrauterine devices, bilateral tubal occlusion, true sexual abstinence in line with the preferred and usual lifestyle of the participant, or vasectomised partner). (See additional information / requirements 25. Male participants with partners of child-bearing potential must use highly effective contraception and are required to use barrier contraception plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least three months after the last dose of MTL-CEBPA. Male participants will also be advised to abstain from sexual intercourse with pregnant or lactating women, or to use condoms. Male participants with partners of child-bearing potential must use highly effective contraception during treatment with sorafenib and for 3 months beyond the last dose of sorafenib, as recommended in sorafenib s USPI. 26. Abstinence is only acceptable if it is line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post- ovulation methods), declaration of abstinence for the duration of exposure to IMP, and withdrawal are not acceptable methods of contraception. 27. Able to comply with all the requirements of the protocol. EXCLUSION CRITERIA: 1. Child-Pugh classification B and C. 2. Participants without a history of hepatitis B and/or hepatitis C. 3. Participants with fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtype HCC. 4. Participants with no prior therapy who are eligible for first-line treatment with atezolizumab in combination with bevacizumab. 5. Participants who received investigational drug(s) within the last 30 days prior to study treatment initiation. 6. Participants with clinically significant ascites. 7. Any episode of bleeding from oesophageal varices or other uncontrolled bleeding including clinically meaningful epistaxis within the last 3 months prior to study treatment initiation. 8. Clinically diagnosed hepatic encephalopathy in the last 6 months unresponsive to therapy. 9. Participants with a history of gastrointestinal haemorrhage or perforation. 10. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated such metastases may participate provided they are radiologically stable for at least 4 weeks by repeat imaging performed during study screening, clinically stable and without requirement of steroid treatment for at least 28 days prior to first dose of study intervention. MRI brain scan are required for all participants with stable brain metastases at screening (CT scan will be allowed if MRI is contraindicated). 11. Participants administered with serum albumin within the last 7 days prior to the first study treatment administration. 12. Known infection with human immunodeficiency virus (HIV) with CD4+ T-cell counts <350 cells/microL or with a history of AIDS-defining opportunistic infection. No HIV testing is required unless mandated by local health authority. 13. Received a live vaccine within 30 days prior to the first dose of study treatment. Live vaccines include, but are not limited to: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist ) are live attenuated vaccines and are not allowed. 14. Known other malignancy that is progressing or has required active treatment in the last 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death such as early-stage cancers treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy. 15. Participants presenting with a baseline prolongation of QT/QTc interval defined as repeated demonstration of a QTc interval >= 450ms (males) and >= 460ms (females) using Fridericia s correction formula. 16. Participants with a screening diastolic blood pressure >90 mm Hg. 17. Clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted. 18. Major surgery within the last 30 days prior to study treatment initiation. If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention. 19. Participants with a history of organ transplantation 20. Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy. 21. Participants with sepsis, ineffective biliary drainage with or without cholangitis, obstructive jaundice, or encephalopathy at screening visi t or within the last 2 weeks prior to study treatment initiation. 22. Evidence of spontaneous bacterial peritonitis or renal failure, or allergic reaction at screening visit or within the last two weeks prior to study treatment initiation, whichever is earlier. 23. Pregnant or lactating women. 24. Known hypersensitivity to the active substance or to any of the excipients of both MTL-CEBPA and sorafenib. 25. History or evidence of any other condition or therapy, including a known psychiatric or substance abuse disorder that, in the judgment of the investigator, may interfere with the study conduct or confound the results, pose a risk to the participant, is not their best interest to take part, or may affect their ability to follow the protocol specific procedures for the duration of the study.
1. Written informed consent obtained prior to any specific trial-related procedure.
2. Male or female 18 years or older.
3. Histologically confirmed advanced HCC with cirrhosis in a participant with a history of hepatitis B and/or C. Participants with past or ongoing HCV infection will be eligible for the study. Participants must have completed their treatment at least 1 month prior to starting study intervention and their HCV viral load below the limit of quantification. Participants who are HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution will be eligible. Participants with past or controlled ongoing hepatitis B will be eligible as long as their HBV viral load is less than 500 IU/mL prior to first dose of study drug. Participants on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study intervention.
4. Child-Pugh classification A.
5. Unsuitable for liver tumour resection and/or refractory to loco-regional therapy.
6. Not eligible for liver transplantation.
7. Had progression or recurrence of HCC following previous treatment with atezolizumab in combination with bevacizumab.
8. Naive to tyrosine kinase inhibitors, including sorafenib, regorafenib, cabozantinib, and lenvatinib.
9. Participants with BCLC stage C disease. BCLC Stage B will be allowed if not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach.
10. Eastern Cooperative Oncology Group performance status of 0 or 1.
11. Has the ability to swallow and retain oral medication.
12. At least one measurable liver lesion (RECIST v1.1) assessed by the investigator.
13. Platelet count >70 x10^9/L.
14 Serum albumin >=28g/L.
15. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=5 x the upper limit of normal (ULN).
16. Bilirubin <=50 Micromol /L.
17. White Blood Cell (WBC) >=2.0 x 10^9/L.
18. Absolute neutrophil count >=1.5 x 10^9/L.
19. Haemoglobin >=9.0 g/dL.
20. International Normalized Ratio (INR) <1.5.
21. Calculated creatinine clearance >=50 mL/min (Cockcroft & Gault).
22. AEs due to prior therapy must have resolved to Grade <=1 (except alopecia or endocrinopathies that are adequately managed through hormone replacement treatment).
23. Negative blood pregnancy test for women of childbearing potential (within 10 days prior to first drug administration).
Note: a woman is considered of child-bearing potential following menarche and until becoming post-menopausal unless permanently sterile. Permanent methods of sterilisation include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A post-menopausal state is defined as no menses for 12 months without an alternative medical cause.
24. Female participants of childbearing potential must use highly effective* contraceptive measures adequate to prevent a new pregnancy for the duration of the study treatment with MTL-CEBPA and sorafenib and, in addition, for at least six months after the last dose of MTL-CEBPA and six months beyond the last dose of sorafenib, as recommended in sorafenib s U.S. Package Insert (USPI). For women with reproductive potential who use a hormonal method of contraception, concurrent use of a second (barrier) method is recommended.
* Highly effective methods of birth control are defined as those that result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly (e.g. implants, injectables, oral contraceptives, some intrauterine devices, bilateral tubal occlusion, true sexual abstinence in line with the preferred and usual lifestyle of the participant, or vasectomised partner). (See additional information / requirements
25. Male participants with partners of child-bearing potential must use highly effective contraception and are required to use barrier contraception plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least three months after the last dose of MTL-CEBPA. Male participants will also be advised to abstain from sexual intercourse with pregnant or lactating women, or to use condoms.
Male participants with partners of child-bearing potential must use highly effective contraception during treatment with sorafenib and for 3 months beyond the last dose of sorafenib, as recommended in sorafenib s USPI.
26. Abstinence is only acceptable if it is line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post- ovulation methods), declaration of abstinence for the duration of exposure to IMP, and withdrawal are not acceptable methods of contraception.
27. Able to comply with all the requirements of the protocol.
EXCLUSION CRITERIA:
1. Child-Pugh classification B and C.
2. Participants without a history of hepatitis B and/or hepatitis C.
3. Participants with fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtype HCC.
4. Participants with no prior therapy who are eligible for first-line treatment with atezolizumab in combination with bevacizumab.
5. Participants who received investigational drug(s) within the last 30 days prior to study treatment initiation.
6. Participants with clinically significant ascites.
7. Any episode of bleeding from oesophageal varices or other uncontrolled bleeding including clinically meaningful epistaxis within the last 3 months prior to study treatment initiation.
8. Clinically diagnosed hepatic encephalopathy in the last 6 months unresponsive to therapy.
9. Participants with a history of gastrointestinal haemorrhage or perforation.
10. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated such metastases may participate provided they are radiologically stable for at least 4 weeks by repeat imaging performed during study screening, clinically stable and without requirement of steroid treatment for at least 28 days prior to first dose of study intervention. MRI brain scan are required for all participants with stable brain metastases at screening (CT scan will be allowed if MRI is contraindicated).
11. Participants administered with serum albumin within the last 7 days prior to the first study treatment administration.
12. Known infection with human immunodeficiency virus (HIV) with CD4+ T-cell counts <350 cells/microL or with a history of AIDS-defining opportunistic infection. No HIV testing is required unless mandated by local health authority.
13. Received a live vaccine within 30 days prior to the first dose of study treatment. Live vaccines include, but are not limited to: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist ) are live attenuated vaccines and are not allowed.
14. Known other malignancy that is progressing or has required active treatment in the last 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death such as early-stage cancers treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
15. Participants presenting with a baseline prolongation of QT/QTc interval defined as repeated demonstration of a QTc interval >= 450ms (males) and >= 460ms (females) using Fridericia s correction formula.
16. Participants with a screening diastolic blood pressure >90 mm Hg.
17. Clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
Note: Medically controlled arrhythmia would be permitted.
18. Major surgery within the last 30 days prior to study treatment initiation. If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
19. Participants with a history of organ transplantation
20. Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy.
21. Participants with sepsis, ineffective biliary drainage with or without cholangitis, obstructive jaundice, or encephalopathy at screening visi t or within the last 2 weeks prior to study treatment initiation.
22. Evidence of spontaneous bacterial peritonitis or renal failure, or allergic reaction at screening visit or within the last two weeks prior to study treatment initiation, whichever is earlier.
23. Pregnant or lactating women.
24. Known hypersensitivity to the active substance or to any of the excipients of both MTL-CEBPA and sorafenib.
25. History or evidence of any other condition or therapy, including a known psychiatric or substance abuse disorder that, in the judgment of the investigator, may interfere with the study conduct or confound the results, pose a risk to the participant, is not their best interest to take part, or may affect their ability to follow the protocol specific procedures for the duration of the study.
Principal Investigator
Referral Contact
For more information: