A Study of Sirolimus for Injection (Albumin Bound) in Patients With Advanced Solid Tumors

A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Antitumor Activity of Sirolimus for Injection (Albumin Bound) in Patients With Advanced Solid Tumors

The purpose of this study is to estimate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of Sirolimus for Injection (Albumin Bound) in patients with solid malignancies.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Sirolimus for Injection (Albumin Bound)

Detailed Description

This study will be conducted in two stages.

Stage 1: To evaluate the safety and tolerability of Sirolimus for Injection (Albumin Bound) in patients with advanced tumors, determine the MTD and RP2D. The dose escalation scheme using the accelerated titration design for dose 1 and the rolling-six design for the remaining doses.

Stage 2: To preliminarily assess the antitumor activity of Sirolimus for Injection (Albumin Bound). Patients will be assigned to different cohorts based on their tumor type.

• Study Type: Interventional
• Enrollment (Anticipated): 264
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xuekun Yao; Phone Number: 0311-67808678; Email: yaoxuekun@mail.ecspc.com
• Study Contact Backup: Name: Yue Huang; Email: huangyue@mail.ecspc.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Medical University Cancer Institute and Hospital
      • Contact: Jihui Hao; Email: haojihui@tjmuch.com
      • Contact: Yehui Shi; Email: shiyehui@tjmuch.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-75 years (inclusive), no gender limitation.
2. Patients must have a histologically or cytologically confirmed advanced or metastatic tumor for which no effective standard therapy is available, or have failed or been intolerant to standard therapies.
3. At least one measurable lesion per RECIST version 1.1.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2.
5. Life expectancy of ≥3 months.
6. Suitable organs and hematopoietic function should be available. Laboratory tests during screening should meet the appropriate criteria.
7. Signed informed consent form.

Exclusion Criteria:

1. Prior anticancer treatment or participation in another clinical study within 4 weeks (or 5 half-lives of the treated drug, whichever is longer) prior to the first dose of study drugs.
2. Patients who have undergone major surgery within 4 weeks prior to starting study treatment, or who have not fully recovered from previous surgery.
3. Unresolved toxicities from prior therapy greater than Grade 1 as per Common Terminology Criteria for Adverse Events (CTCAE) (except alopecia or any other toxicity without safety risks as judged by the investigator).
4. History of serious cardiovascular disease.
5. Central nervous system metastasis or meningeal metastasis with clinical symptoms, or other evidence that the patient's central nervous system metastasis or meningeal metastasis has not been controlled, and the investigator judges it to be unsuitable for inclusion.
6. Known prior hypersensitivity to study drugs or any component in their formulations.
7. Prior treatment with any mTOR inhibitor.
8. Has received a live or live-attenuated virus vaccine within 30 days prior to consent.
9. Uncontrollable active infection (CTCAE v5.0 ≥grade 2).
10. Use of strong inhibitors and inducers of CYP3A4 within 2 weeks prior to receiving the first dose of study drug and still need to continue using this class of drug.
11. History of autoimmune diseases, immunodeficiency, including HIV positive, or other acquired, congenital immunodeficiency, or organ transplant history.
12. HBsAg-positive with HBV viral load (VL) ≥1000 IU/mL; Hepatitis C Virus (HCV)-positive; Anti-treponema pallidum positive.
13. Women of child-bearing potential, or men whose partners are women of childbearing age, have not agree to use highly effective methods of contraception during dosing and for 6 months after study drug discontinuation; female patients has a positive serum pregnancy test within 7 days prior to receiving the first dose of study medication; lactating female.
14. Has history of other serious diseases judged by the investigator, which will threaten the safety of patients or interfere the study compliance, or other reasons are not suitable for participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sirolimus for Injection (Albumin Bound); Stage 1：Multiple doses of Sirolimus for Injection (Albumin Bound) will be administered intravenously. Stage 2：RP2D of Sirolimus for Injection (Albumin Bound) as determined during stage 1 will be administered intravenously.	Drug: Sirolimus for Injection (Albumin Bound); Sirolimus for Injection (Albumin Bound), intravenously, once a week, 28 days per cycle (three weeks-on and one week-off)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events	Up to 3 years
Dose-Limiting Toxicities (Stage 1)	Cycle 1 (Up to 28 days)
Maximum tolerated dose (Stage 1)	Up to 1.5 years
Recommended phase 2 dose (Stage 1)	Up to 1.5 years
Overall response rate (Stage 2)	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of Response	Up to 3 years
Progression-free Survival	Up to 3 years
Area under the plasma concentration versus time curve (AUC)	Day 1 of cycle 1 to Day 1 of cycle 4 (85 days)
Peak concentration (Cmax)	Day 1 of cycle 1 to Day 1 of cycle 4 (85 days)
Peak time (Tmax)	Day 1 of cycle 1 to Day 1 of cycle 4 (85 days)
Distribution volume (Vz)	Day 1 of cycle 1 to Day 1 of cycle 4 (85 days)
Elimination half-life (t1/2)	Day 1 of cycle 1 to Day 1 of cycle 4 (85 days)
Clearance (CL)	Day 1 of cycle 1 to Day 1 of cycle 4 (85 days)
Disease Control Rate	Up to 3 years
4ebp-1 phosphorylation level in blood samples	Up to 168 hours post dose
S6K phosphorylation level in blood samples	Up to 168 hours post dose
TSC1/2 status in tumor samples	Day 1 of cycle 1
PTEN status in tumor samples	Day 1 of cycle 1
PIK3CA status in tumor samples	Day 1 of cycle 1

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Investigators: Principal Investigator: Jihui Hao, Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2021
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: October 25, 2021
• First Submitted That Met QC Criteria: November 8, 2021
• First Posted (Actual): November 18, 2021

Study Record Updates

• Last Update Posted (Actual): January 25, 2022
• Last Update Submitted That Met QC Criteria: January 22, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Sirolimus for Injection (Albumin Bound)
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: HB1901-CSP-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No