TheraSphere With Durvalumab and Tremelimumab for HCC (ROWAN)

P
Paul Haste

Primary Investigator

Overview

The objective of the ROWAN clinical study is to assess the efficacy of local tumor control in HCC patients who receive TheraSphere followed by durvalumab and tremelimumab.

Description

A global open-label, prospective, multi-center Phase II trial designed to assess the safetyd efficacy of TheraSphere administered before initiation of Durvalumab with Tremelimumab in HCC patients who are not a candidate for resection, thermal ablation or liver transplant athe time of study entry.

Eligibility

You may be eligible for this study if you meet the following criteria:

  • Conditions:
    Hepatocellular Carcinoma
  • Age: 18 Years
  • Gender: All

Inclusion Criteria:
  1. Participants must be aged ≥18 years at the time of screening.
  2. Written informed consent and any locally required authorization (e.g., Healthurance Portability and accountability Act in the US, European Union (EU) datavacy regulations in the EU) obtained from the patient/legal representative prior tog any protocol-related procedures, including screening evaluations.
  3. Life expectancy ≥6 months.
  4. HCC, diagnosed by radiographic imaging or histology.
  5. Patient not a candidate for liver resection, thermal ablation, or transplantation athe time of study entry.
  6. ECOG 0 or 1
  7. Measurable disease by mRECIST criteria (e.g. ≥10mm of enhancement).
  8. Tumor volume ≤35% of whole liver volume (determined by imaging).
  9. Future liver remnant volume (FLRV) ≥30% of whole liver volume. FRLV is the volume ofver not planned to be treated with TheraSphere and free of HCC.
  10. Dosimetry criteria for tumor(s) and normal tissue can be determined.
  11. Patients with previous liver resection or ablation ≥6 months from end of previousTheraSphere administration.
  12. Previous transarterial chemoembolization (TACE) is permitted if:
    1. Previous TACE performed ≥8 months before TheraSphere administration and
    2. Result of previous TACE was CR and
    3. Current tumor is not a recurrence of previously treated lesion
  13. Patients with portal vein thrombosis (PVT) Vp0, Vp1, or Vp2.
  14. Patients with HBV or HCV infection are to have documented virology status of hepatitisd by HBV and HCV serology test:
    1. Patients with HBV infection: HBV DNA load should be ≤2000 IU/mL obtained within2 days prior to initiation of study treatment, and Anti-HBV treatment (per localdard of care; e.g., entecavir) for a minimum of 14 days prior to study entryd willingness to continue treatment for the length of the study
    2. Patients with chronic HCV infection are allowed in the study: for untreatedAST/ALT should be ≤3xULN and for treated patients, antiviral treatment(per local standard of care) should be stopped for a minimum of 14 days prior toudy entry and AST/ALT should be ≤3xULN
  15. Patients with Human Immunodeficiency Virus (HIV) infection are eligible, provided the
    HIV infection is well controlled with no current or previous AIDS-relatedd CD4+ T-cell (CD4+) counts ≥ 350 cells/uL
  16. Negative serum pregnancy test in females of childbearing potential.
  17. Adequate contraception for the patient and his/her sexual partner.
  18. Adequate renal and marrow function as defined below:
    1. Hemoglobin (hgB) ≥9.0 g/dL
    2. Absolute neutrophil count (ANC) ≥1.5 x 109/L
    3. Platelet count ≥75 x 109/L
    4. Measured or calculated creatinine clearance ≥45 mL/min as determined byCockcroft-Gault (using actual body weight)
  19. Absolute lymphocyte count ≥0.5 X 109/L
  20. Adequate liver function, as defined by
    1. Child-Pugh A
    2. Albumin-bilirubin (ALBI) score 1 or 2 with upper limit for ALBI score ≤ -2.Patients with confirmed Gilbert's syndrome may not have an evaluable bilirubinvalue; therefore, ALBI score should not be considered for such patients. Patientswith Gilbert's syndrome will be eligible with any bilirubin value, as long asAlbumin level is ≥ 34 g/L.
    3. AST and ALT <3 x ULN.
  21. Body weight >30 kg and BMI ≥18 kg/m2.
Exclusion Criteria:
  1. Any contraindication to angiography or selective visceral catheterization.
  2. Cone Beam CT (CBCT) or Technetium-99m macroaggregated Albumin (99mTc-MAA) hepaticusion scintigraphy shows any deposition to the gastrointestinal tracthat may not be corrected by angiographic techniques.
  3. 99mTc-MAA hepatic arterial perfusion scintigraphy shows poor tumor and/or portal veinhrombosis (PVT) targeting that would lead to a dose that does not meet the liverdosing criteria.
  4. Shunting of blood to the lungs that could result in delivery of >30 Gy to the lungs ingle treatment or >50 Gy cumulative dose to the lungs in case of multipleTheraSphere treatments, as seen on 99mTc-MAA hepatic arterial perfusion scintigraphy.
  5. Vp3, Vp4, hepatic vein invasion, or inferior vena cava (IVC) invasion
  6. Extrahepatic metastases (patients with extrahepatic spread [EHS]):
    1. EHS is any extrahepatic lesion that, according to clinical symptoms, histology,ging data, is highly suspicious of being metastases.
    2. For patients with bone pain/neurological symptoms (deficit, seizure or else) atbaseline and suspected of metastases at screening, a bone scan/brain MRI isded prior to study entry.
    3. Extrahepatic non-target non-measurable lesions (<1 cm per RECIST 1.1) areble if considered not suspicious by the investigator.
  7. Any previous systemic HCC treatment
  8. Prior exposure to immune mediated therapy for other disease, such as other anti-PD- 1,PDL-1, anti-PDL-2, anti-CTLA-4, antibodies, etc.
  9. Previous liver radiation (external beam radiation therapy (EBRT) or peptide receptordionuclide therapy (PRRT)).
  10. Concurrent treatment for HCC or treatment in the last 4 weeks in another clinicaludy, unless it is an observational study (non-interventional) or during aventional follow-up stage of an interventional study, or prior inclusion inhis study
  11. Hepatic encephalopathy present at study entry and/or episodes of encephalopathy (Grade≥ 2) within 6 months prior to study inclusion.
  12. HCC with infiltrative disease that is not evaluable by mRECIST.
  13. Pulmonary insufficiency (defined by an arterial oxygen pressure (PaO2) of <60 mmHg, orygen saturation (SaO2) of <90% (Roussos & Koutsoukou, 2003) or clinically evidenthronic obstructive pulmonary disease (COPD)).
  14. Medical history of radiation pneumonitis or recent pneumonitis, regardless ofusality
  15. History of any organ allograft, including bone marrow allo and autograft.
  16. History of active primary/acquired immunodeficiency, that makes patients unsuitabledditional immunotherapy in this study (per investigator and as detailed inusion criterion #18).
  17. Active or prior documented autoimmune or inflammatory disorders (including but notd to, inflammatory bowel disease [e.g. ulcerative colitis or Crohn's disease],ystemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis,hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
    1. Patients with vitiligo or alopecia
    2. Patients with hypothyroidism (e.g. following Hashimoto's syndrome) stable onhormone replacement therapy
    3. Any chronic skin condition that does not require systemic therapy.
    4. Patients without active disease in the last 5 years may be included but onlyultation with the Sponsor Study physician.
    5. Patients with celiac disease controlled by diet alone.
  18. Current or prior use of immunosuppressive medication within 14 days before the first
    dose of durvalumab. The following are exceptions to this criterion:
    1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g.ular injection)
    2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day ofdnisone or its equivalent.
    3. Steroids as premedication for hypersensitivity reactions (e.g. CT scandication).
  19. History of gastrointestinal bleeding within 42 days prior to study inclusion, active
    GI bleeding and any bleeding diathesis or coagulopathy that is not correctable byusual therapy or hemostatic agents (e.g. closure device). Patients with known variceshat have not bled or which have been clinically addressed can enter the study. Nodoscopic exploration is required before study inclusion.
  20. Presence of biliary stent or sphincterotomy within one year prior to study inclusion.
  21. History of malignancy, other than HCC, within three years, except the condition is onehe following:
    1. Adequately treated carcinoma in situ of the cervix, early squamous cell carcinomabasal cell carcinoma of the skin, localized prostate cancer, breast ductalu, or low-grade endometrial carcinoma with no myometrial invasion
    2. Localized prostate cancer under active surveillance.
    3. Other cancer when there is a negligible risk of recurrence or progression ordeath (5-year OS rate > 90%).
  22. Major surgical procedure (as defined by the Investigator) within 42 days prior to
    study inclusion.
  23. A history of severe allergy or intolerance to contrast agents, narcotics, sedatives orhat cannot be managed medically.
  24. Known allergy or hypersensitivity to any of the study drugs or any of the study drughat cannot be managed medically.
  25. Active infection including tuberculosis (clinical evaluation that includes clinicalhistory, physical examination and radiographic findings, and tuberculosis testing inwith local practice), HBV and HVC co-infection, HBV and Hep D co-infection, humanunodeficiency virus (HIV 1/2 antibodies) plus HCV or HBV co-infection.
  26. Receipt of live attenuated vaccine within 30 days prior to the first dose ofdurvalumab and/or tremelimumab. Note: patients, if enrolled, should not receive livevaccine whilst receiving durvalumab and/or tremelimumab and up to 30 days after thedose of durvalumab and/or tremelimumab.
  27. Female patients who are pregnant or breastfeeding and who do not want to stopbreastfeeding. Male or female patients of reproductive potential who are not willingy any effective birth control method from screening and for at least 90 daysTheraSphere administration, 90 days after the last dose of durvalumab, and 6hs after the last dose of tremelimumab.
  28. Unstable chronic disease or evidence of any disease or condition that would place theundue risk and preclude safe use of TheraSphere, durvalumab andumab treatment as deemed by the site principal investigator.
  29. Patients who are not able to follow the TheraSphere, durvalumab or tremelimumabquirements.
    For France Patients Only
  30. Persons deprived of their liberty by a judicial or administrative decision, personsubject to psychiatric care under articles L. 3212-1 and L. 3213-1 who are not coveredby the provisions of Article L. 1121-8 and persons admitted to a health or socialblishment for purposes other than research, including:
    1. Pregnant, parturient, breast-feeding women (see also inclusion criterion 16 andusion criterion 27)
    2. Minors (see also inclusion criterion 1)
    3. Persons receiving psychiatric treatment (see also exclusion criteria 28)
    4. Persons admitted to a health or social establishment for purposes other thanh
    5. Person of full age under curatorship
    6. Adult subject to a mandate for future protection, a family authorization, or aguardianship measure
    7. Person not affiliated or not beneficiary of a social security scheme

Updated on 29 Apr 2024. Study ID: S2472
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