Trial Title:
Open-Label Study of the CDK4/6 Inhibitor SPH4336 in Subjects With Locally Advanced or Metastatic Liposarcomas
NCT ID:
NCT05580588
Condition:
Liposarcoma, Dedifferentiated
Conditions: Official terms:
Liposarcoma
Conditions: Keywords:
CDK4/6 inhibitor
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Open-label
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
SPH4336
Description:
400 mg SPH4336 PO QD
Arm group label:
SPH4336
Summary:
Study SPH4336-US-01 is an open-label (no placebo), multicenter clinical trial to evaluate
the safety, blood levels (pharmacokinetics) and preliminary anti-tumor effects of
SPH4336, a selective enzyme blocker, in patients with specific types of liposarcomas
(tumors expressing the target of the study drug).
Detailed description:
Study SPH4336-US-01 is a multicenter, non-randomized, open-label Phase 2 study of SPH4336
with a safety lead-in in subjects with CDK4-positive liposarcomas (dedifferentiated or
well-differentiated/dedifferentiated liposarcomas). SPH4336 is an orally administered,
molecularly targeted chemotherapy drug called a cyclin-dependent kinase inhibitor (CDK4/6
inhibitor), which acts to block the ability of cancer cells to divide and thus prevents
tumors from growing. SPH4336 (tablets) will be administered orally once each day in
successive 28-day cycles until demonstration of progressive disease or the development of
unacceptable toxicity.
The study will incorporate a safety lead-in for the initial 10 subjects. Safety will be
evaluated after 10 subjects (minimum 1 cycle completed) by a Safety Review Committee
(SRC). The study will be stopped if unacceptable toxicity is observed in more than 2
subjects.
Tumor assessments according to RECIST v1.1 will be performed at baseline and every 6
weeks (from Cycle 1, Day 1 (C1D1)) for 36 weeks, then every 12 weeks thereafter. Plasma
samples for pharmacokinetics will be collected in all subjects. Baseline (pretreatment)
tumor tissue (archival or fresh) will be collected from all subjects to confirm
histologically a liposarcoma with a dedifferentiated component and CDK4 positivity. Tumor
tissue biomarkers (e.g., phospho-Rb, Ki-67) will be analyzed in the first 10 study
subjects in baseline (pretreatment) and C1D15 tumor tissue samples.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Informed consent
- ≥ 18 years of age
- ECOG performance status 0 or 1
- Histologically confirmed, locally advanced or metastatic sarcoma
- Dedifferentiated or well-differentiated/dedifferentiated liposarcomas
- No more than 3 prior lines of treatment
- Evidence of progression as evidenced by at least one of the following within the
past 3 months:
- An increase of at least 20% in measurable tumors
- The appearance of new lesions
- Unequivocal progression of non-measurable lesions
- Measurable disease per RECIST v1.1
- If residual treatment-related toxicity from prior therapy:
- All treatment-related toxicity resolved to Grade 1 or baseline (alopecia
excepted)
- ANC ≥ 1,500/μL
- Platelets ≥ 100,000/μL
- Hgb ≥ 9.0 g/dL (in the absence of pRBC transfusion over the prior 4 weeks)
- Estimated glomerular filtration rate of ≥ 60 mL/min (based on the Cockcroft and
Gault formula for individualized estimates of GFR)
- Total bilirubin ≤ 1.5 x the Upper Limit of Normal (ULN) or ≤ 3 x ULN if known
Gilbert's disease
- AST and ALT ≤ 3 x ULN or ≤ 5 x ULN if malignant involvement of the liver
- Sterile or willing to use effective contraception (approved hormonal contraceptive
such as oral contraceptives, patches, implants, injections, rings or
hormonally-impregnated intrauterine device (IUD), or an IUD in women of childbearing
potential and a condom in men) during the study and for 3 months following the last
dose of study drug
- Availability of archived tumor tissue or willingness to undergo a baseline tumor
biopsy, and in the first 10 study subjects, to determine baseline tumor biomarker
levels and a willingness to undergo a second tumor biopsy at C1D15 to assess
treatment-induced changes in tumor biomarker levels
Exclusion Criteria:
- Prior treatment with a CDK4/6-targeted agent
- Patient's tumor known to be CDK4 negative
- Anticancer therapy (e.g., chemotherapy, biologics, irradiation) within 14 days or 5
half-lives (whichever is greater) of screening
- Major surgery within 28 days of screening
- Requirement for systemic treatment with strong CYP3A4 inhibitors or inducers of
CYP3A4 at study entry
- Central nervous system metastases or leptomeningeal disease, unless appropriately
treated and neurologically stable without steroids for ≥ 28 days
- Other malignancy unless disease-free for ≥ 2 years and not expected to relapse or
require treatment during study participation
- Active systemic infection or severe localized infection
- Known HIV-positive with CD4+ cell counts < 350 cells/uL or a history of an
AIDS-defining opportunistic infection
- Known hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with viral load
above the limit of quantification
- Active COVID-19 infection
- Major cardiac abnormalities (e.g., uncontrolled angina, unstable arrhythmias,
myocardial infarction, NYHA Class ≥ 3 CHF) ≤ 6 months of C1D1
- Persistent (3 ECGs ≥ 5 mins apart) prolongation of the QTcF (Fridericia) > 470 msec
- [Females] Pregnant or nursing
- Any other medical or psychiatric condition, or laboratory abnormality that would
result in an unacceptable risk with study participation
- Presence of active gastrointestinal disease or other condition expected to interfere
significantly with absorption, distribution, metabolism or excretion of oral therapy
(e.g., ulcerative disease, uncontrolled nausea, vomiting, chronic diarrhea,
malabsorption syndrome)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic Hospital
Address:
City:
Phoenix
Zip:
85054
Country:
United States
Status:
Recruiting
Contact:
Last name:
Mahesh Seetharam, MD
Phone:
840-301-8000
Email:
Seetharam.Mahesh@Mayo.edu
Facility:
Name:
City of Hope
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Adam Rock, MD
Phone:
626-218-9200
Email:
arock@coh.org
Facility:
Name:
Mayo Clinic Florida
Address:
City:
Jacksonville
Zip:
32224
Country:
United States
Status:
Recruiting
Contact:
Last name:
Steven Attia, DO
Email:
Attia.Steven@mayo.edu
Facility:
Name:
University of Miami
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Emily E Jonczak, MD
Email:
Emily.Jonczak@Med.Miami.edu
Facility:
Name:
University of Michigan
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Status:
Recruiting
Contact:
Last name:
Scott M Schuetze, MD
Email:
scotschu@med.umich.edu
Facility:
Name:
Hackensack University Medical Center
Address:
City:
Hackensack
Zip:
07601
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrew Pecora, MD
Phone:
515-996-5885
Email:
Andrew.Pecora@HMHN.org
Facility:
Name:
Seidman Cancer Center, University Hospitals
Address:
City:
Cleveland
Zip:
44106
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ankit Mangla, MD
Phone:
312-513-7437
Email:
axm1297@case.edu
Facility:
Name:
The Ohio State University
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gabriel Tinoco, MD
Email:
Gabriel.Tinoco@osumc.edu
Facility:
Name:
Vanderbilt University Medical Center
Address:
City:
Nashville
Zip:
37232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Vicki Keedy, MD
Phone:
615-322-4967
Email:
Vicki.Keedy@VUMC.org
Start date:
August 31, 2023
Completion date:
March 2025
Lead sponsor:
Agency:
Shanghai Pharma Biotherapeutics USA Inc.
Agency class:
Industry
Source:
Shanghai Pharma Biotherapeutics USA Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05580588
