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Open-Label Study for Safety, Tolerability, PK 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

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ClinicalTrials.gov Identifier: NCT04676633
Recruitment Status : Recruiting
First Posted : December 21, 2020
Last Update Posted : May 26, 2021
Sponsor:
Collaborator:
Translational Drug Development
Information provided by (Responsible Party):
Sirnaomics

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

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Liver Metastases Cholangiocarcinoma Drug: STP705 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Accelerated titration design followed by expansion to standard 3+3 design
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 1, 2021
Estimated Primary Completion Date : March 1, 2024
Estimated Study Completion Date : May 31, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: STP705
Investigational Product

Experimental: Cohort 2: STP705 40 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.
Drug: STP705
Investigational Product

Experimental: Cohort 3: STP705 80 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.
Drug: STP705
Investigational Product

Experimental: Cohort 4: STP705 160 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.
Drug: STP705
Investigational Product

Experimental: Cohort 5: STP705 320 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.
Drug: STP705
Investigational Product




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: 28 day cycle ]
    Recommended starting dose & schedule

  2. Limited Dose Toxicity (LTD) [ Time Frame: 28 day cycle ]
    Recommended starting dose & dose escalation



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  2. Measurable disease per RECIST v 1.1 (primary or metastatic disease)
  3. ECOG performance status or 0 - 1
  4. Life expectancy of at least 3 months
  5. Age ≥ 18 years
  6. Signed, written Institutional Review Board (IRB) approved informed consent
  7. A negative serum pregnancy test (for nonsterile women of child-bearing potential)
  8. Baseline Q-T corrected interval (QTc) interval of ≤ 480 msec using Frederica's formula
  9. 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
  10. Acceptable renal function, defined as:

    o Serum creatinine ≤ 1.5 ULN or Creatinine Clearance ≥ 30 mL/minute

  11. Acceptable hematologic status:

    • Hemoglobin ≥ 8 g/dL (a transfusion is allowed if Hemoglobin stays stable thereafter)
    • Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3
    • Platelet count ≥100,000 plt/mm3 x 109/ L (≥ 65,000 if low platelet counts are due to splenic sequestration and portal hypertension)
  12. Urinalysis with no clinically significant abnormalities
  13. Acceptable coagulation status with partial thromboplastin time (PTT) and International Normalized Ratio (INR) ≤1.5 times upper limit of normal
  14. Subject has adequate vitamin D level, as defined by serum total 25-Hydroxyvitamin D [25(OH)D] ≥ 20 to < 60 ng/mL
  15. Completion of all previous treatments (including surgery, systemic chemotherapy and radiotherapy), as well as supportive care (including transfusion of blood, blood components and granulocyte colony-stimulation factor [G-CSF] treatment) at least 3 weeks before screening (6 weeks for nitrosoureas or mitomycin C), with no signs or symptoms of acute toxicity > Grade 1 (except alopecia)
  16. For men and women of child-producing potential, the use of effective contraceptive methods during the study
  17. No aspirin for ≥ 5 days in advance of intra-tumoral administration, as well as discontinuation of antiplatelet and anticoagulant medications for the appropriate amount of time

Exclusion Criteria:

  1. 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
  2. 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
  3. Hepatocellular carcinoma patients with a Child Pugh score > B7
  4. Had paracentesis in the last 3 months; presence of ascites must be controlled by diuretics
  5. History of hepatic encephalopathy in the last 6 months
  6. History of variceal bleeding in the last 6 months
  7. Concomitant medications that are strong inhibitors or inducers of CYP450 enzymes that cannot be stopped or replaced during the study
  8. 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.)
  9. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
  10. 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.
  11. Participation in a clinical study involving administration of an investigational compound within the past 30 days prior to study entry.
  12. Previous intratumoral injection within the past 30 days prior to study entry.
  13. Unwillingness or inability to comply with procedures required in this protocol
  14. Known allergy or hypersensitivity to the study drug(s) or one of the ingredients in the formulation
  15. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04676633


Contacts
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Contact: nadia sheibani 301-740-1730 nadiasheibani@sirnaomics.com

Locations
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United States, Arizona
Honor Health Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Paul McKinney    480-323-3805    pmkinney@honorhealth.com   
Principal Investigator: Sunil Sharma, MD         
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Mengsha Li    626-218-0494    meli@coh.org   
Principal Investigator: Jonathan Kessler         
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Xiomara Menendez    323-865-0212    menendez_x@med.usc.edu   
Principal Investigator: Anthony El-Khoueiry, MD         
United States, Connecticut
Hartford Healthcare Recruiting
Hartford, Connecticut, United States, 06106
Contact: Priyanaka Abraham    860-972-5018    Priyanka.Abraham@hhchealth.org   
Principal Investigator: Jessica Clement, MD         
United States, New Jersey
Atlantic Health System Recruiting
Morristown, New Jersey, United States, 07960
Contact: Christine koranyi    862-881-9131    christine.koranyi@atlantichealth.org   
Principal Investigator: Angela Allistar, MD         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Katy Schroeder    414-805-8843    kbaxheowswe@mcw.edu   
Principal Investigator: Ben Goeorge, MD         
Sponsors and Collaborators
Sirnaomics
Translational Drug Development
Investigators
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Study Director: Nadia Sheibani Sirnaomics
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Responsible Party: Sirnaomics
ClinicalTrials.gov Identifier: NCT04676633    
Other Study ID Numbers: SRN-705-005
First Posted: December 21, 2020    Key Record Dates
Last Update Posted: May 26, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Neoplasm Metastasis
Carcinoma, Hepatocellular
Liver Neoplasms
Cholangiocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplastic Processes
Pathologic Processes
Adenocarcinoma
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases