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Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Anti-tumor Activity of FN-1501 Monotherapy in Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03690154
Recruitment Status : Recruiting
First Posted : October 1, 2018
Last Update Posted : October 1, 2018
Sponsor:
Information provided by (Responsible Party):
Shanghai Fosun Pharmaceutical Development Co, Ltd.

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.


Condition or disease Intervention/treatment Phase
Advanced Cancer Solid Tumor Drug: FN-1501 Phase 1

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 1 week rest, 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Multi-center, Open-label, Single-arm, Dose-escalation, Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Anti-tumor Activity of FN-1501 Monotherapy in Patients With Advanced Solid Tumors
Actual Study Start Date : July 23, 2018
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Arm Intervention/treatment
Experimental: FN-1501 Drug: FN-1501
Eligible patients will receive a single intravenous infusion of study drug on Days 1, 3, 5, 8, 10, and 12 of a 21-day cycle. Dosing will begin at 2.5 mg once per day on the assigned days. Dose escalation will use the traditional 3+3 design and follow a modified Fibonacci sequence until the pre-determined highest dose of 35 mg/day or MTD is reached. At least 3 patients will be enrolled in each cohort. Administration of FN- 1501 will be continued until disease progression, intolerable toxicity, withdrawal of consent, or termination according to the Principal Investigator's judgment or at the sponsor's request.




Primary Outcome Measures :
  1. 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. ]
  2. 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 Outcome Measures :
  1. Area under the plasma concentration-time curve from zero to the last measurable concentration (AUC0-last) [ Time Frame: During the first year. ]
  2. Area under concentration-time curve from 0 to 24 hours (AUC(0-24)) [ Time Frame: During the first year. ]
  3. Area under the plasma concentration time curve from zero to infinity (AUC0-∞) [ Time Frame: During the first year. ]
  4. Maximum observed plasma concentration (Cmax) [ Time Frame: During the first year. ]
  5. Time to maximum observed plasma concentration (tmax) [ Time Frame: During the first year. ]
  6. Terminal half-life (t1/2) [ Time Frame: During the first year. ]
  7. Clearance (CL) [ Time Frame: During the first year. ]
  8. Apparent volume of distribution (Vd) [ Time Frame: During the first year. ]
  9. Measurement of anti-tumor activity of FN-1501 according to RECIST version 1.1 (solid tumor) [ Time Frame: During the first year. ]
  10. Measurement of anti-tumor activity of FN-1501 including but not limited to CT/MRI images [ Time Frame: During the first year. ]


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.


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

Inclusion Criteria:

  • Male and female of 18 years old and above
  • Able to understand and sign consent form
  • Patients with histologically or cytologically confirmed advanced solid tumors who have relapsed or refractory disease 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
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
  • Have discontinued all previous cancer therapies for at least 21days or 5 half-lives prior to study treatment, whichever is shorter, and recovered from the acute adverse effects of therapy
  • Expected survival of at least 2 months
  • LVEF ≥ 50% and QTc interval < 450 ms
  • Women shall meet either of the following conditions before enrollment
  • Infertile, defined as having a bilateral oophorectomy (ovariectomy), or a bilateral tubal ligation, or being post-menopausal for at least 1 year.
  • For those of childbearing potential, they should have a negative serum pregnancy test during screening, agree to refrain from lactation, and use effective contraception such as hormonal methods associated with inhibition of ovulation, condom, intra-uterine device, surgical sterilization (including partner's vasectomy) or sexual abstinence during the study and 30 days after the last administration of study drug.
  • Men who are engaging or plan to engage in sexual activity with a female of childbearing potential must either have a prior vasectomy or agree to use effective contraception such as condoms, sexual abstinence and appropriate methods taken by their partners during the study and 90 days after the last dose.
  • Patients must have adequate organ functions as indicated by the following screening laboratory values:
  • Serum total bilirubin ≤ 1.5 × upper limit normal (ULN) (Serum total bilirubin can be ≤ 3.0 × ULN if patients have hemolysis or congenital hemolytic diseases)
  • Creatinine < 1.5 × ULN or estimated creatinine clearance ≥ 50 mL/min
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN or

    • 5 X ULN for patient with liver metastases
  • Absolute neutrophil count (ANC) ≥ 1.5×10^9/L
  • Platelets ≥ 100×10^9/L
  • Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L (Note: Criteria must be met without a transfusion within 2 weeks of obtaining the sample)

Exclusion Criteria:

  • Participation in another therapeutic clinical trial within 3 weeks of enrollment
  • Previous toxic reactions to cancer therapy and have not recovered within 2 weeks of enrollment (> NCI CTCAE 4.03 Grade 2)
  • Having received a major surgical operation within 4 weeks of enrollment or not completely recovered from a previous operation
  • Any serious or uncontrollable systemic disease, including but not limited to: Hypertension (after treatment, systolic pressure > 180 mmHg and/or diastolic pressure > 100 mmHg) and active hemorrhagic disorders; patients who are determined by investigators as otherwise not suitable for participation in this study
  • 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

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): NCT03690154


Contacts
Contact: Te Li 021-33987583 lit@fosunpharma.com

Locations
United States, Kansas
KUMC Cancer Center Recruiting
Fairway, Kansas, United States, 66205
Contact: Stephen K Williamson, MD    913-945-5059    swilliam@kumc.edu   
Principal Investigator: Stephen K Williamson, MD         
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48334
Contact: Ulka Vaishampayan, MD    248-538-4701    vaishamu@karmanos.org   
Principal Investigator: Ulka Vaishampayan, MD         
Australia, Victoria
Cabrini Malvern Hospital Recruiting
Malvern, Victoria, Australia, 3144
Contact: Gary E Richardson, MD    1 300-300-977    gary.richardson@ocv.net.au   
Principal Investigator: Gary E Richardson, MD         
Sponsors and Collaborators
Shanghai Fosun Pharmaceutical Development Co, Ltd.
  Study Documents (Full-Text)

Documents provided by Shanghai Fosun Pharmaceutical Development Co, Ltd.:
Study Protocol  [PDF] May 1, 2018


Responsible Party: Shanghai Fosun Pharmaceutical Development Co, Ltd.
ClinicalTrials.gov Identifier: NCT03690154     History of Changes
Other Study ID Numbers: FN-1501-UP1
First Posted: October 1, 2018    Key Record Dates
Last Update Posted: October 1, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No