Phase 1 Multicenter, Open-Label, Dose Escalation Study and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of STP705 Administered Intratumorally in Cholangiocarcinoma, Hepatocellular Carcinoma or Liver Metastases in Subjects With Advanced/Metastatic or Surgically Unresectable Solid Tumors Who Are Refractory to Standard Therapy

Sirnaomics4 sites in 1 country5 target enrollmentMarch 1, 2021

ConditionsHepatocellular Carcinoma Liver Metastases Cholangiocarcinoma

InterventionsSTP705

DrugsSTP705

Overview

Phase: Phase 1
Intervention: STP705
Conditions: Hepatocellular Carcinoma
Sponsor: Sirnaomics
Enrollment: 5
Locations: 4
Primary Endpoint: Maximum Tolerated Dose (MTD)
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of STP705 administered intratumorally in cholangiocarcinoma, hepatocellular carcinoma or liver metastasis in subjects with advanced/metastatic or surgically unresectable solid tumors who are refractory to standard therapy.

Goals:

To determine the MTD or RP2D of STP705 when administered intratumorally into cholangiocarcinoma, hepatocellular carcinoma, or liver metastasis.
To establish the dose of STP705 recommended for future phase 2 studies when administered intratumorally.

Detailed Description

This is an open label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of various doses of STP705 administered intratumorally in cholangiocarcinoma, hepatocellular carcinoma or liver metastasis. The primary objective of this study is to determine the MTD or RP2D of STP705 and to establish the dose of STP705 recommended for future phase 2 studies when administered intratumorally. A total of up to 30 patients will be enrolled in the dose escalation phase of the study. In addition, once the MTD or recommended phase 2 dose has been established, up to 20 additional patients maybe enrolled to confirm safety and explore anti-tumor activity. Up to five dose levels will be explored (20,40,80,160,320 μg dose levels) and will depend on the number and intensity of observed toxicity. Intermediate doses maybe explored during escalation period. It will follow an accelerated titration design, enrolling 1 patient per dose cohort and will expand to a standard 3+3 design after. In the accelearted titration a Grade 2 SE triggers the transition to the 3+3 part of the study. The 3+3 part of the study will start at dose level 160μg. Subjects will be evaluated for DLTs in the first cycle of treatment and graded aacording to NCI CTCAE v5. A cycle is 28 days.

Registry

clinicaltrials.gov

Start Date

March 1, 2021

End Date

January 13, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Sirnaomics

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects with histologically or cytologically confirmed advanced/metastatic or surgically unresectable cholangiocarcinoma, hepatocellular carcinoma, or other solid malignancy with one or more qualifying liver metastases who are refractory to standard therapy
•Have at least one liver tumor or metastasis (≤ 5 cm in size) that is not sub-capsular and not near any major blood vessel
•Have no more than 7 liver lesions
•Is deemed safe for percutaneous intra-tumoral injection by local radiologist
•Measurable disease per RECIST v 1.1 (primary or metastatic disease)
•ECOG performance status or 0 - 1
•Life expectancy of at least 3 months
•Age ≥ 18 years
•Signed, written Institutional Review Board (IRB) approved informed consent
•A negative serum pregnancy test (for nonsterile women of child-bearing potential)

Exclusion Criteria

•New York Heart Association Class III or IV cardiac disease, or myocardial infarction, severe unstable angina, coronary/peripheral artery bypass graft, congestive heart failure within the past 6 months
•Known active, uncontrolled infection with HIV or hepatitis B; patients with hepatitis B allowed if on anti-viral therapy and have a viral load ≤ 500 IU; patients with a history of HIV must be on antiretroviral therapy for at least four weeks and have an HIV viral load ≤ 400 copies/mL, have CD4+ T cell counts ≥ 350 cells/uL and no history of AIDS-defining opportunistic infections within 3 months prior to treatment
•Hepatocellular carcinoma patients with a Child Pugh score \> B7
•Had paracentesis in the last 3 months; presence of ascites must be controlled by diuretics
•History of hepatic encephalopathy in the last 6 months
•History of variceal bleeding in the last 6 months
•Concomitant medications that are strong inhibitors or inducers of CYP450 enzymes that cannot be stopped or replaced during the study
•Major surgical procedure within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study. (Note: Placement of a central venous access catheter(s) (e.g., port or similar) is not considered a major surgical procedure.)
•Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
•Pregnant or nursing women. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Arms & Interventions

Cohort 1: STP705 20 μg dose

Intratumoral injection, administered as a single agent on Day 1,8 and 15 of a 28-day cycle. If the patient is deriving clinical benefit from the agent it may be continued and will be administered on Day 1 of each successive cycle.

Intervention: STP705