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A Phase 1, Dose Escalation Study in Subjects With Advanced or Metastatic Solid Tumor and Moderate Liver Impairment

NCT04617522

Description:

This is a Phase 1, multi-center, open-label, dose-escalation study of sacituzumab govitecan in adult subjects with advanced or metastatic solid tumor and moderate hepatic impairment or normal hepatic function. Up to 20 subjects with moderate hepatic impairment defined according to the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria (i.e., 1.5× upper limit of normal [ULN] <total bilirubin <3.0× ULN) and 8 subjects with normal hepatic function will be enrolled. Eligible subjects will receive sacituzumab govitecan intravenous (IV) infusion over 3 hours on Day 1 and Day 8.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1, Dose Escalation Study in Subjects With Advanced or Metastatic Solid Tumor and Moderate Liver Impairment
  • Official Title: A Phase 1, Open-Label, Dose-Escalation Study to Determine an Appropriate Starting Dose of Sacituzumab Govitecan in Subjects With Advanced or Metastatic Solid Tumor and Moderate Liver Impairment

Clinical Trial IDs

  • ORG STUDY ID: Immu-132-15
  • NCT ID: NCT04617522

Conditions

  • Advanced or Metastatic Solid Tumor
  • Liver Failure

Interventions

DrugSynonymsArms
sacituzumab govitecanSubjects with Advanced or Metastatic Solid Tumor and Moderate Liver Impairment

Purpose

This is a Phase 1, multi-center, open-label, dose-escalation study of sacituzumab govitecan in adult subjects with advanced or metastatic solid tumor and moderate hepatic impairment or normal hepatic function. Up to 20 subjects with moderate hepatic impairment defined according to the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria (i.e., 1.5× upper limit of normal [ULN] <total bilirubin <3.0× ULN) and 8 subjects with normal hepatic function will be enrolled. Eligible subjects will receive sacituzumab govitecan intravenous (IV) infusion over 3 hours on Day 1 and Day 8.

Detailed Description

      Subjects with moderate hepatic impairment will undergo dose escalation following a 3+3 study
      design. Dose escalation will occur if fewer than 33% of subjects within the dosing group
      experienced a dose-limiting toxicity. The starting sacituzumab govitecan dose will be 5
      mg/kg. If the starting dose is not acceptably tolerated, a lower dose of sacituzumab
      govitecan may need to be evaluated. Sacituzumab govitecan doses to be studied will be 5, 7.5,
      and 10 mg/kg Dose escalation will only occur if it is deemed to be acceptable after review of
      safety data up to Day 22. Once the recommended dose is determined, additional subjects with
      moderate hepatic impairment will be added, for a total of 8 subjects receiving the
      recommended dose. In addition, 8 subjects with normal hepatic function will receive
      sacituzumab govitecan 10 mg/kg. Serial blood samples will be collected on Day 1 and Day 8 for
      up to 7 days after dosing for PK assessments. Safety will be evaluated throughout the study.
      Subjects may be confined in the study center from the evening of Day 1 to Day 4 and Day 8 to
      Day 11 at the discretion of the Investigator. Subjects will report to the study center on the
      study days for study procedures. Subjects will exit the study on Day 38. At the completion of
      the study, subjects who are deriving benefit from sacituzumab govitecan may continue to
      receive treatment in a rollover study (IMMU-132-14). Otherwise, all subjects must complete an
      End-of-Study (EOS) visit approximately 30 days after the last dose of the study drug.
    

Trial Arms

NameTypeDescriptionInterventions
Subjects with Advanced or Metastatic Solid Tumor and Moderate Liver ImpairmentExperimentalSubjects with moderate hepatic impairment will be enrolled at each dose level. The dose-escalation plan will start at 5 mg/kg sacituzumab govitecan and escalate to 7.5mg/kg and finally 10 mg/kg if deemed to be safe.
  • sacituzumab govitecan
Subjects with Advanced or Metastatic Solid Tumor and Normal Liver functionExperimental8 subjects with normal hepatic function will receive sacituzumab govitecan 10 mg/kg
  • sacituzumab govitecan

Eligibility Criteria

        Inclusion Criteria for all subjects:

          1. Male or female subjects aged at least 18 years of age, at the time of signing the
             informed consent.

          2. Histologically confirmed advanced or metastatic solid tumor that is measurable or
             nonmeasurable.

          3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.

          4. Adequate hematologic counts without transfusional or growth factor support within 2
             weeks of study drug initiation (hemoglobin ≥9 g/dL, absolute neutrophil count (ANC)
             ≥1,500/mm3, and platelets ≥100,000/ μL).

          5. Creatinine clearance ≥30 mL/min as assessed by the Cockcroft-Gault equation 6 . For
             patients with normal hepatic function must have a Normal hepatic function (total
             bilirubin ≤ULN and aspartate aminotransferase [AST] ≤3.0× ULN).

        7. Moderate hepatic impairment (1.5× ULN <total bilirubin <3.0× ULN and any level of AST).

        8. For subjects with hepatic encephalopathy, the condition does not, in the Investigator's
        opinion, interfere with the subject's ability to provide an appropriate informed consent.

        Exclusion Criteria:

          1. Have poor venous access

          2. donated or lost 500mL or more of blood volume (including plasmapheresis) to plans to
             donate during the study

          3. Have had a prior anticancer biologic agent within 4 weeks prior to Day 1 or have had
             prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2
             weeks prior to Day 1 and who have not recovered (i.e., ≤Grade 2) from adverse events
             (AEs) at the time of study entry. Subjects participating in observational studies are
             eligible.

        2. Had prior treatment with irinotecan within 4 weeks prior to Day 1 3. Have not recovered
        (i.e., ≤Grade 1) from AEs due to a previously administered agent 4. Have an active second
        malignacy 5. Have known active central nervous system (CNS) metastases and/or carcinomatous
        meningitis. Subjects with previously treated brain metastases may participate provided they
        have stable CNS disease for at least 4 weeks prior to the first dose of study drug and all
        neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain
        metastases, and are taking ≤20 mg/day of prednisone or its equivalent. All subjects with
        carcinomatous meningitis are excluded regardless of clinical stability.

        6. Have active cardiac disease 7. Have active chronic inflammatory bowel disease
        (ulcerative colitis or Crohn's disease) or gastrointestinal (GI) perforation within 6
        months of enrollment 8. Have active serious infection requiring intravenous antibiotics
        (Contact medical monitor for clarification) 9. High-dose systemic corticosteroids (≥20 mg
        of prednisone or its equivalent) are not allowed within 2 weeks of Check-In. However,
        inhaled, intranasal, intra-articular, and topical steroids are allowed.

        10. Use of strong inhibitor or inducer of UGT1A1 11. Have a history of Gilbert's disease 12
        For patients with normal hepatic functions must have pre-existing condition interfering
        with hepatic and/or renal function that could interfere with the metabolism and/or
        excretion of the study drug 13. Have AST or alanine aminotransferase (ALT) >1.5× ULN;
        alkaline phosphatase or bilirubin ≥1.5× ULN (isolated bilirubin >1.5× ULN is acceptable if
        bilirubin is fractionated and direct bilirubin <35%). A single repeat is allowed for
        eligibility determination 14. Had a clinical exacerbation of liver disease within the
        2-week period before administration of study drug (i.e., abdominal pain, nausea, vomiting,
        anorexia, or fever) 15. Had clinically demonstrable, tense ascites 16. Had evidence of
        acute viral hepatitis within 1 month prior to administration of study drug 17. Have
        evidence of hepatorenal syndrome 18. Subjects with transjugular intrahepatic portosystemic
        shunt (TIPS) placement.

        19. Have active Stage 3 or 4 encephalopathy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Identify a safe starting dose
Time Frame:through Day 38
Safety Issue:
Description:To identify the safe starting dose of sacituzumab govitecan in subjects with solid tumor and moderate hepatic impairment

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gilead Sciences

Last Updated

April 13, 2021