Safety, Tolerability, PK, Anti-Tumor Activity of STP705 in Subjects With Advanced/Metastatic or Surgically Unresectable Solid Tumors Who Are Refractory to Standard Therapy

NCT04676633 | Completed Phase 1 FDA Drug

• 1 other identifier: SRN-705-005
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 4

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:

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

Conditions

Hepatocellular Carcinoma; Liver Metastases; Cholangiocarcinoma

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  Recommended starting dose \& schedule

  28 day cycle

• Limited Dose Toxicity (LTD)

  Recommended starting dose \& dose escalation

  28 day cycle

Study Arms (5)

Cohort 1: STP705 20 μg dose

EXPERIMENTAL

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.

Drug: STP705

Cohort 2: STP705 40 μg dose

EXPERIMENTAL

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.

Drug: STP705

Cohort 3: STP705 80 μg dose

EXPERIMENTAL

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.

Drug: STP705

Cohort 4: STP705 160 μg dose

EXPERIMENTAL

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.

Drug: STP705

Cohort 5: STP705 320 μg dose

EXPERIMENTAL

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.

Drug: STP705

Interventions

STP705 DRUG

Investigational Product

Also known as: STP705 POWDER FOR INJECTION

Cohort 1: STP705 20 μg dose; Cohort 2: STP705 40 μg dose; Cohort 3: STP705 80 μg dose; Cohort 4: STP705 160 μg dose; Cohort 5: STP705 320 μg dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Baseline Q-T corrected interval (QTc) interval of ≤ 480 msec using Frederica's formula
• Acceptable liver function:
• Bilirubin ≤ 1.5 times upper limit of normal
• AST (SGOT), ALT (SGPT) and Alkaline phosphatase ≤ 5 times upper limit of normal because of cancer or metastases to the liver
• Acceptable renal function, defined as:

You may not qualify if:

• 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.
• Participation in a clinical study involving administration of an investigational compound within the past 30 days prior to study entry.
• Previous intratumoral injection within the past 30 days prior to study entry.
• Unwillingness or inability to comply with procedures required in this protocol
• Known allergy or hypersensitivity to the study drug(s) or one of the ingredients in the formulation
• Existence of any surgical, medical or laboratory condition that, in the judgment of the clinical investigator, might interfere with the safety, distribution, metabolism or excretion of the drug

Sponsors & Collaborators

• Sirnaomics: lead
• Translational Drug Development: collaborator

Study Sites (4)

Honor Health

Scottsdale, Arizona, 85258, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Atlantic Health System

Morristown, New Jersey, 07960, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Cholangiocarcinoma

Interventions

Injections

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Francois Lebel, MD

  Chief Medical Officer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Accelerated titration design followed by expansion to standard 3+3 design

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: December 21, 2020
• Study Start: March 1, 2021
• Primary Completion: January 13, 2023
• Study Completion: January 13, 2023
• Last Updated: March 19, 2024

Record last verified: 2024-03

Locations

US (4)