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

Liver Failure Clinical Trial

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT04617522
• Other study ID #: IMMU-132-15
• Status: Recruiting
• Phase: Phase 1
• Start date: April 6, 2021
• Est. completion date: November 2023

Study information

• Verified date: November 2023
• Source: Gilead Sciences
• Contact: Gilead Clinical Study Information Center
• Phone: 1-833-445-3230 (GILEAD-0)
• Email: GileadClinicalTrials[@]gilead.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: November 2023
• Est. primary completion date: November 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumor
• Liver Failure

Intervention

Drug:
• Sacituzumab Govitecan-hziy
Administered intravenously

Locations

Country	Name	City	State
France	Centre Leon Berard	Lyon
United States	NEXT Austin	Austin	Texas
United States	University of Maryland	Baltimore	Maryland
United States	Oncology Consultants, P.A.	Houston	Texas
United States	The University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	Pacific Shores Medical Group	Long Beach	California
United States	Christiana Care Health Services	Newark	Delaware
United States	NEXT Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  France, 

References & Publications (5)

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. — View 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. — View 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. — View Citation

Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants experiencing Treatment Emergent Adverse Events (TEAEs)		First dose date up to Day 38
Primary	Percentage of Participants Experiencing Any Clinically Significant Laboratory Abnormalities		First dose date up to Day 38
Primary	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.	Days 1 and 8
Primary	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.	Days 1 and 8
Primary	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.	Days 1 and 8
Primary	Percentage of Participants who Develop Positive Anti-Sacituzumab Govitecan-hziy Antibodies		Day 1 (Predose) and Day 22

External Links

•   Gilead Clinical Trials Website