A Phase 1, Multi-center, Open-label, Single-arm, Dose-escalation, Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of FN-1501 Monotherapy in Patients With Advanced Solid Tumors or Relapsed/Refractory Acute Myeloid Leukemia (AML)
Overview
- Phase
- Phase 1
- Intervention
- FN-1501
- Conditions
- Advanced Cancer
- Sponsor
- Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
- Enrollment
- 67
- Locations
- 3
- Primary Endpoint
- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
This research study is being done in people with advanced-stage solid tumor cancer. Advanced stage solid tumor cancer is a cancer that forms an abnormal mass of tissue that usually does not contain cysts or liquid areas. Different types of solid tumors are named for the type of cells that form them. Examples of solid tumors include lung cancer, breast cancer, prostate cancer, kidney cancer, colorectal cancer, melanoma and sarcoma.
The purpose of this research study is to evaluate the safety of the investigational study drug, FN-1501, at different dose levels. FN-1501 has not previously been given to human subjects. It is intended for the treatment in this study of patients with advanced solid tumor cancers. This study will determine the effects, good and/or bad, on patients' cancer. The main objective of this study is to define the recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of FN-1501. The MTD is the highest dose a person can take without having bad side effects, and the RP2D will be the dose of FN-1501 used in future studies.
Detailed Description
This is a phase 1, first-in-human, open-label, multicenter, dose escalation study. Dose escalation will follow the traditional 3+3 design. Patients will be screened for eligibility for up to 28 days prior to entry into the study. The starting dose will be 2.5 mg/day (once daily). The period for DLT assessment is 21 days from the first dose of FN-1501. Evaluation of a cohort of at least three (3) patients completing DLT assessment at any given dose level is required prior to determining the next dose level and dose regimen for the subsequent cohort. After the first patient in the cohort receives the Cycle 1, Day 1 dose, subsequent patients in that cohort will not be dosed until the first patient has been evaluated for at least 48 hours to exclude unexpected acute toxicity. The continuous safety evaluation will be performed by investigators, the medical monitor, and the sponsor. A Safety Monitoring Committee (SMC) will determine dose levels to be administered and dose regimen during dose escalation based on the data available from the previous dose levels. If an MTD is not identified due to paucity of DLTs, the RP2D will be determined based on pharmacokinetics, safety, tolerability, and preliminary efficacy. If a patient wishes to continuously receive study treatment on completion of Cycle 1, the patient can continue study treatment in 21-day Cycle 2 and subsequent cycles (same as Cycle 2, all of 21 days' duration), defined as administration of 3 times per week for 2 weeks followed by one week off, at the discretion of the investigator. The primary endpoint of this study is to determine the recommended phase 2 dose (RP2D) of FN-1501 based on pharmacokinetics, safety and tolerability, as well as preliminary efficacy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female 18 years old and above
- •Able to understand and sign informed consent form
- •Patients with histologically or cytologically confirmed advanced solid tumors who have relapsed or refractory disease or relapsed/refractory AML for which no standard therapies expected to produce clinical benefit to the patient are available
- •Patients with diagnosed solid tumors must have at least one lesion that is measurable per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
- •Patients with relapsed or refractory AML must be diagnosed with AML based on World Health Organization (WHO) criteria (≥ 20% blasts in bone marrow). Patients with acute promyelocytic leukemia are excluded
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- •Have discontinued all previous cancer therapies for at least 21 days or 5 half-lives prior to study treatment, whichever is shorter, and recovered from the acute adverse effects of therapy
- •Expected to survive at least 2 to 3 months
- •LVEF ≥ 50% and QTc interval \< 450 ms
- •Women shall meet either of the following conditions before enrollment
Exclusion Criteria
- •Participation in another therapeutic clinical trial within 3 weeks of enrollment
- •A previous toxicity-related reaction towards cancer therapy have not recovered within 2 weeks of enrollment (\>Grade 2 National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03)
- •Having received a major surgical operation within 4 weeks of enrollment or not yet completely recovered from a previous operation
- •Any serious or uncontrollable systemic disease, including but not limited to: Hypertension (after treatment, systolic blood pressure (SBP) \> 180 mmHg and/or diastolic blood pressure (DBP) \> 100 mmHg) and active hemorrhagic disorders; patients who are determined by investigators as otherwise not suitable for participation in this study.Note: Patients that in the judgment of the investigator have clinical signs of disease progression during the screening period (i.e.: febrile neutropenia, ascites requiring drainage, hospitalization due to worsening underlying disease, etc.) will not be eligible for participation.
- •Active known infection, including hepatitis B, hepatitis C, and human immunodeficiency virus
- •Primary central nervous system (CNS) tumor or CNS metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (patients with a history of CNS metastases or cord compression are allowable if they have been definitively treated and have been clinically stable for at least 3 months, and off steroids or anticonvulsants ≥ 2 weeks before first dose of study drug)
- •Serious kidney injury, requiring dialysis
- •Serious liver injury, and advanced liver diseases of Child-Pugh class B and C
- •On medications that are strong cytochrome P450(CYP)3A inhibitors or inducers unless patients are willing and able to change to use of an equivalent medication that is not a strong CYP3A inhibitor or inducer
- •Cardiac function and disease history which meets one or more of the following conditions:
Arms & Interventions
FN-1501
Intervention: FN-1501
Outcomes
Primary Outcomes
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03
Time Frame: From first dose until 30 days after the last dose.
To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D)
Time Frame: During the first year.
The recommended phase 2 dose (RP2D) of FN-1501 will be determined based on pharmacokinetics, safety and tolerability, as well as preliminary efficacy.
Secondary Outcomes
- Maximum observed plasma concentration (Cmax)(During the first year.)
- Area under the plasma concentration-time curve from zero to the last measurable concentration (AUC0-last)(During the first year.)
- Area under concentration-time curve from 0 to 24 hours (AUC(0-24))(During the first year.)
- Area under the plasma concentration time curve from zero to infinity (AUC0-∞)(During the first year.)
- Time to maximum observed plasma concentration (tmax)(During the first year.)
- Terminal half-life (t1/2)(During the first year.)
- Clearance (CL)(During the first year.)
- Apparent volume of distribution (Vd)(During the first year.)
- Measurement of anti-tumor activity of FN-1501 according to RECIST version 1.1 (solid tumor)(During the first year.)
- Measurement of anti-tumor activity of FN-1501 including but not limited to CT/MRI images(During the first year.)