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Study of Sacituzumab Govitecan in Participants With Advanced or Metastatic Solid Tumor and Moderate Liver Impairment

Primary Purpose

Advanced or Metastatic Solid Tumor, Liver Failure

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Sacituzumab Govitecan-hziy
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced or Metastatic Solid Tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria for all Individuals:

  • Histologically confirmed advanced or metastatic solid tumor that is measurable or nonmeasurable.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
  • 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/mm^3, and platelets ≥ 100,000/ μL).
  • Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation

Key Inclusion Criteria for Individuals with Normal Hepatic Function:

  • Normal hepatic function (total bilirubin ≤ ULN and aspartate aminotransferase [AST] ≤ 3.0× ULN).

Key Inclusion Criteria for Individuals with Moderate Hepatic Function:

  • Moderate hepatic impairment (1.5 × ULN < total bilirubin < 3.0 × ULN and any level of AST).
  • For individuals with hepatic encephalopathy, the condition does not, in the Investigator's opinion, interfere with the individual's ability to provide an appropriate informed consent.

Key Exclusion Criteria for all Individuals:

  • Have poor venous access
  • Donated or lost 500mL or more of blood volume (including plasmapheresis) to plans to donate during the study
  • 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. Individuals participating in observational studies are eligible.
  • Had prior treatment with irinotecan within 4 weeks prior to Day 1
  • Have not recovered (i.e., ≤ Grade 1) from AEs due to a previously administered agent
  • Have an active second malignancy
  • Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Individuals 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 individuals with carcinomatous meningitis are excluded regardless of clinical stability.
  • Have history of cardiac disease
  • Have active chronic inflammatory bowel disease (ulcerative colitis or Crohn's disease) or gastrointestinal (GI) perforation within 6 months of enrollment
  • Have active serious infection requiring intravenous antibiotics (Contact medical monitor for clarification)
  • 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.
  • Use of strong inhibitor or inducer of UGT1A1
  • Have a history of Gilbert's disease

Key Exclusion Criteria for Individuals with Normal Hepatic Impairment:

  • 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

Key Exclusion Criteria for Individuals with Moderate Hepatic Impairment:

  • 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)
  • Had clinically demonstrable, tense ascites
  • Had evidence of acute viral hepatitis within 1 month prior to administration of study drug
  • Have evidence of hepatorenal syndrome
  • Individuals with transjugular intrahepatic portosystemic shunt (TIPS) placement.
  • Have active Stage 3 or 4 encephalopathy

Sites / Locations

  • Pacific Shores Medical Group
  • Christiana Care Health Services
  • University of Maryland
  • NEXT Austin
  • Oncology Consultants, P.A.Recruiting
  • The University of Texas M.D. Anderson Cancer CenterRecruiting
  • NEXT OncologyRecruiting
  • Centre Leon Berard

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Advanced or Metastatic Solid Tumor and Moderate Liver Impairment

Advanced or Metastatic Solid Tumor and Normal Liver function

Arm Description

Participants with advanced solid tumor and moderate hepatic impairment will receive an escalating dose of sacituzumab govitecan-hziy on Days 1 and 8. The dose-escalation plan will start at 5 mg/kg and escalate to 7.5 mg/kg, and finally 10 mg/kg, if deemed to be safe. At the completion of study treatment, participants who are deriving benefit from sacituzumab govitecan-hziy may continue to receive treatment in a Gilead sponsored rollover study (IMMU-132-14; NCT04319198).

Participants with advanced or metastatic solid tumor and normal hepatic function will receive sacituzumab govitecan-hziy 10 mg/kg on Days 1 and 8. At the completion of study treatment, participants who are deriving benefit from sacituzumab govitecan-hziy may continue to receive treatment in a Gilead sponsored rollover study (IMMU-132-14; NCT04319198).

Outcomes

Primary Outcome Measures

Percentage of Participants experiencing Treatment Emergent Adverse Events (TEAEs)
Percentage of Participants Experiencing Any Clinically Significant Laboratory Abnormalities
PK Parameter: Cmax of Free SN-38, SN-38 Glucuronide, Total SN-38, and Sacituzumab Govitecan-hziy
Cmax will be determined for 4 analytes: Free SN-38, SN-38 glucuronide, Total SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. Cmax is defined as the maximum observed concentration obtained directly from the observed concentration-time data.
PK Parameter: AUC_last of Free SN-38, SN-38 Glucuronide, Total SN-38, and Sacituzumab Govitecan-hziy
AUC_last will be determined for 4 analytes: Free SN-38, SN-38 glucuronide, Total SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC_last is defined as area under the serum concentration-time curve from time 0 to time of the last quantifiable concentration of the 4 analytes.
PK Parameter: AUC_0-168 of Free SN-38, SN-38 Glucuronide, Total SN-38, and Sacituzumab Govitecan-hziy
AUC_0-168 will be determined for 4 analytes: Free SN-38, SN-38 glucuronide, Total SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-168 is defined as area under the serum concentration-time curve from time 0 to 168 hours.
Percentage of Participants who Develop Positive Anti-Sacituzumab Govitecan-hziy Antibodies

Secondary Outcome Measures

Full Information

First Posted
November 2, 2020
Last Updated
October 9, 2023
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT04617522
Brief Title
Study of Sacituzumab Govitecan in Participants 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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 6, 2021 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
November 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The goals of this clinical study are to learn more about the safety and dosing of the study drug, sacituzumab govitecan-hziy, in participants with solid tumors and moderate liver problems.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced or Metastatic Solid Tumor, Liver Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Advanced or Metastatic Solid Tumor and Moderate Liver Impairment
Arm Type
Experimental
Arm Description
Participants with advanced solid tumor and moderate hepatic impairment will receive an escalating dose of sacituzumab govitecan-hziy on Days 1 and 8. The dose-escalation plan will start at 5 mg/kg and escalate to 7.5 mg/kg, and finally 10 mg/kg, if deemed to be safe. At the completion of study treatment, participants who are deriving benefit from sacituzumab govitecan-hziy may continue to receive treatment in a Gilead sponsored rollover study (IMMU-132-14; NCT04319198).
Arm Title
Advanced or Metastatic Solid Tumor and Normal Liver function
Arm Type
Experimental
Arm Description
Participants with advanced or metastatic solid tumor and normal hepatic function will receive sacituzumab govitecan-hziy 10 mg/kg on Days 1 and 8. At the completion of study treatment, participants who are deriving benefit from sacituzumab govitecan-hziy may continue to receive treatment in a Gilead sponsored rollover study (IMMU-132-14; NCT04319198).
Intervention Type
Drug
Intervention Name(s)
Sacituzumab Govitecan-hziy
Other Intervention Name(s)
IMMU-132, GS-0132
Intervention Description
Administered intravenously
Primary Outcome Measure Information:
Title
Percentage of Participants experiencing Treatment Emergent Adverse Events (TEAEs)
Time Frame
First dose date up to Day 38
Title
Percentage of Participants Experiencing Any Clinically Significant Laboratory Abnormalities
Time Frame
First dose date up to Day 38
Title
PK Parameter: Cmax of Free SN-38, SN-38 Glucuronide, Total SN-38, and Sacituzumab Govitecan-hziy
Description
Cmax will be determined for 4 analytes: Free SN-38, SN-38 glucuronide, Total SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. Cmax is defined as the maximum observed concentration obtained directly from the observed concentration-time data.
Time Frame
Days 1 and 8
Title
PK Parameter: AUC_last of Free SN-38, SN-38 Glucuronide, Total SN-38, and Sacituzumab Govitecan-hziy
Description
AUC_last will be determined for 4 analytes: Free SN-38, SN-38 glucuronide, Total SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC_last is defined as area under the serum concentration-time curve from time 0 to time of the last quantifiable concentration of the 4 analytes.
Time Frame
Days 1 and 8
Title
PK Parameter: AUC_0-168 of Free SN-38, SN-38 Glucuronide, Total SN-38, and Sacituzumab Govitecan-hziy
Description
AUC_0-168 will be determined for 4 analytes: Free SN-38, SN-38 glucuronide, Total SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-168 is defined as area under the serum concentration-time curve from time 0 to 168 hours.
Time Frame
Days 1 and 8
Title
Percentage of Participants who Develop Positive Anti-Sacituzumab Govitecan-hziy Antibodies
Time Frame
Day 1 (Predose) and Day 22

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria for all Individuals: Histologically confirmed advanced or metastatic solid tumor that is measurable or nonmeasurable. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. 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/mm^3, and platelets ≥ 100,000/ μL). Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation Key Inclusion Criteria for Individuals with Normal Hepatic Function: Normal hepatic function (total bilirubin ≤ ULN and aspartate aminotransferase [AST] ≤ 3.0× ULN). Key Inclusion Criteria for Individuals with Moderate Hepatic Function: Moderate hepatic impairment (1.5 × ULN < total bilirubin < 3.0 × ULN and any level of AST). For individuals with hepatic encephalopathy, the condition does not, in the Investigator's opinion, interfere with the individual's ability to provide an appropriate informed consent. Key Exclusion Criteria for all Individuals: Have poor venous access Donated or lost 500mL or more of blood volume (including plasmapheresis) to plans to donate during the study 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. Individuals participating in observational studies are eligible. Had prior treatment with irinotecan within 4 weeks prior to Day 1 Have not recovered (i.e., ≤ Grade 1) from AEs due to a previously administered agent Have an active second malignancy Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Individuals 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 individuals with carcinomatous meningitis are excluded regardless of clinical stability. Have history of cardiac disease Have active chronic inflammatory bowel disease (ulcerative colitis or Crohn's disease) or gastrointestinal (GI) perforation within 6 months of enrollment Have active serious infection requiring intravenous antibiotics (Contact medical monitor for clarification) 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. Use of strong inhibitor or inducer of UGT1A1 Have a history of Gilbert's disease Key Exclusion Criteria for Individuals with Normal Hepatic Impairment: 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 Key Exclusion Criteria for Individuals with Moderate Hepatic Impairment: 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) Had clinically demonstrable, tense ascites Had evidence of acute viral hepatitis within 1 month prior to administration of study drug Have evidence of hepatorenal syndrome Individuals with transjugular intrahepatic portosystemic shunt (TIPS) placement. Have active Stage 3 or 4 encephalopathy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gilead Clinical Study Information Center
Phone
1-833-445-3230 (GILEAD-0)
Email
GileadClinicalTrials@gilead.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Pacific Shores Medical Group
City
Long Beach
State/Province
California
ZIP/Postal Code
90813
Country
United States
Individual Site Status
Suspended
Facility Name
Christiana Care Health Services
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
NEXT Austin
City
Austin
State/Province
Texas
ZIP/Postal Code
78758
Country
United States
Individual Site Status
Withdrawn
Facility Name
Oncology Consultants, P.A.
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of Texas M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
NEXT Oncology
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Name
Centre Leon Berard
City
Lyon
ZIP/Postal Code
69373
Country
France
Individual Site Status
Active, not recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21372224
Citation
Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Goldenberg DM. Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: preclinical studies in human cancer xenograft models and monkeys. Clin Cancer Res. 2011 May 15;17(10):3157-69. doi: 10.1158/1078-0432.CCR-10-2939. Epub 2011 Mar 3.
Results Reference
background
PubMed Identifier
25915780
Citation
Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Arrojo R, Liu D, Rossi EA, Chang CH, Goldenberg DM. Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. Bioconjug Chem. 2015 May 20;26(5):919-31. doi: 10.1021/acs.bioconjchem.5b00223. Epub 2015 May 8.
Results Reference
background
PubMed Identifier
28069724
Citation
Cardillo TM, Sharkey RM, Rossi DL, Arrojo R, Mostafa AA, Goldenberg DM. Synthetic Lethality Exploitation by an Anti-Trop-2-SN-38 Antibody-Drug Conjugate, IMMU-132, Plus PARP Inhibitors in BRCA1/2-wild-type Triple-Negative Breast Cancer. Clin Cancer Res. 2017 Jul 1;23(13):3405-3415. doi: 10.1158/1078-0432.CCR-16-2401. Epub 2017 Jan 9.
Results Reference
background
PubMed Identifier
26101915
Citation
Goldenberg DM, Cardillo TM, Govindan SV, Rossi EA, Sharkey RM. Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC). Oncotarget. 2015 Sep 8;6(26):22496-512. doi: 10.18632/oncotarget.4318. Erratum In: Oncotarget. 2020 Mar 10;11(10):942.
Results Reference
background
PubMed Identifier
1244564
Citation
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580.
Results Reference
background
PubMed Identifier
35728046
Citation
Kwapisz D. Sacituzumab Govitecan-hziy in Breast Cancer. Am J Clin Oncol. 2022 Jul 1;45(7):279-285. doi: 10.1097/COC.0000000000000919. Epub 2022 May 12.
Results Reference
derived
Links:
URL
https://www.gileadclinicaltrials.com/study/?id=IMMU-132-15
Description
Gilead Clinical Trials Website

Learn more about this trial

Study of Sacituzumab Govitecan in Participants With Advanced or Metastatic Solid Tumor and Moderate Liver Impairment

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