Clinical trial NCT05037149: Ph. 1, Evaluation of Safety, Tolerability, PK, Anti-tumor Activity of STP707 IV in Subjects With Solid Tumors
Official title: Ph.1, Open-Label, Dose Escalation & Expansion for Safety, Tolerability, PK, & Anti-Tumor Activity of STP707 Administered IV in Subjects With Advanced/Metastatic or Surgically Unresectable Solid Tumors Who Are Refractory to Standard Therapy.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Sirnaomics
Sponsor class: INDUSTRY
First posted: 2021-09-08
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: One subject will be enrolled at dose level 1. After the first subject has passed the DLT period, defined as 28 days, the second and third subject will be enrolled at least 24 hours apart. If more than 3 subjects have been identified for a given dose level, additional subjects may be enrolled in a lower dose level that has passed the DLT period up to a maximum of 12 subjects per dose level for dose levels 3 and 4 and up to a maximum of 9 subjects for dose levels A and 5. Subjects enrolled to backfill cohorts may be enrolled simultaneously, without a waiting period between subjects.
Primary purpose: TREATMENT

Brief summary: An open label, dose escalation and dose expansion study to evaluate the safety, tolerability, and anti-tumor activity of STP707 with IV administration in subjects with advanced/metastatic or surgically unresectable solid tumors who are refractory to standard therapy.

Detailed description: A phase 1, open label, dose escalation and dose expansion study to evaluate the safety, tolerability, and anti-tumor activity of STP707 with IV administration in subjects with advanced/metastatic or surgically unresectable solid tumors who are refractory to standard therapy.

The primary objective of this study is to determine the MTD or RP2D of STP707 and to establish the dose of STP707 recommended for future phase 2 studies administered intravenously.

A total of 30 subjects will be enrolled in dose escalation. Once MTD or RP2D has been established, up to 10 additional subjects will enrolled to confirm safety and explore anti-tumor activity.

Up to 5 dose levels will be explored (3,6,12,24,48 mg dose levels). Intermediate doses between scheduled dose levels maybe explored during escalation. A cycle is 28 days.

Dose escalation will follow a standard 3+3 design.

Eligibility criteria: Inclusion Criteria:

1. Subjects with histologically or cytologically confirmed advanced / metastatic or surgically unresectable solid tumors whose tumors are refractory to standard therapy
2. Measurable disease per RECIST v 1.1 (primary or metastatic disease)
3. ECOG performance status 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. Acceptable liver function:

   * Bilirubin ≤ 1.5 times upper limit of normal
   * AST (SGOT), ALT (SGPT) ≤ 5 times upper limit of normal because of cancer or metastases to the liver
9. Acceptable renal function, defined as:

   o Serum creatinine ≤ 1.5 ULN or Creatinine Clearance ≥ 50 mL/minute
10. Acceptable hematologic status:

    * Hemoglobin ≥ 9 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
11. Urinalysis with no clinically significant abnormalities
12. Acceptable coagulation status with partial thromboplastin time (PTT) and International Normalized Ratio (INR) ≤ 1.5 times upper limit of normal unless patient is on anticoagulants and has stable PTT and PT that are within normal therapeutic range for disease under management
13. Subject has adequate vitamin D level, as defined by serum total 25-Hydroxyvitamin D \[25(OH)D\] ≥ 20 to \< 60 ng/mL. If subjects are below this threshold, they may receive vitamin D supplementation se per clinic dosing guidelines and may still be enrolled provided they are started on vitamin D supplementation
14. Completion of all previous treatments (including surgery, systemic chemotherapy, and radiotherapy) at least 3 weeks before screening
15. For men and women of child-producing potential, the use of effective contraceptive methods during the study

Exclusion Criteria:

1. Baseline Q-T corrected interval (QTc) interval of \> 470 msec for all subjects calculated using Fridericia's formula
2. 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
3. Known active, uncontrolled infection with HIV or hepatitis B; subjects 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
4. 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.)
5. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
6. 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.
7. Participation in a clinical study involving administration of an investigational compound within the past 30 days prior to study entry.
8. Unwillingness or inability to comply with procedures required in this protocol
9. Known allergy or hypersensitivity to the study drug(s) or one of the ingredients in the formulation (e.g., Trehalose dihydrate)
10. 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: 28 Day Cycle
measure: Limited Dose Toxicity (LDT)
timeFrame: 28 day cycle
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Morristown
country: United States
facility: Atlantic Health System
state: New Jersey
city: Austin
country: United States
facility: NEXT Oncology
state: Texas
Study officials:
affiliation: NEXT Oncology
name: Andrae Vandross, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sarah Cannon Research Institute at HealthONE
name: Jason Henry, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Southern California
name: Anthony El-Khoueiry, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Atlantic Health System
name: Angela Alistar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Hani Babiker, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Michael Cecchini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Conor Steuer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Christina Wu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Zhaohui Jin, MD
role: PRINCIPAL_INVESTIGATOR
References: