A Phase 2/3 Study to Evaluate the Efficacy and Safety of Unesbulin in Unresectable or Metastatic, Relapsed or Refractory Leiomyosarcoma
- Conditions
- Leiomyosarcomamalignant smooth muscle tumor10072990
- Registration Number
- NL-OMON53907
- Lead Sponsor
- PTC Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 10
1. Subject is willing and able to provide informed consent 2. Willingness and
ability to comply with scheduled visits, drug administration plan, laboratory
tests, other study procedures, and study restrictions 3. Disease status
including: a. Histological or cytological confirmation of LMS arising at any
anatomic site except bone sarcoma b. Unresectable or metastatic, relapsed or
refractory disease c. Measurable disease per RECIST 1.1 criteria d. Disease
progression on previous treatment before screening or intolerability to other
oncology treatments Demographics: 4. Age >=18 years 5. Male or female
Performance status: 6. ECOG PS score of 0 or 1 Hematopoietic: 7. Absolute
neutrophil count >=1500/mm3 without the use of growth factors in the past 7 days
8. Platelet count >=100000/mm3 without platelet transfusion in the past 14 days
9. Hemoglobin >=9 g/dL (packed red blood cell transfusion is not allowed within
7 days) Hepatic: 10. Bilirubin <= upper limit of normal (ULN) except for those
patients with Gilbert's syndrome 11. Aspartate aminotransferase or alanine
aminotransferase <3 times the ULN 12. Subjects with liver metastases may be
enrolled Pulmonary: 13. Subjects with well-controlled asthma (eg, use of rescue
medications <2 times per week over the last 12 months) or chronic
obstructive pulmonary disease (eg, no exacerbations over the prior 3 months)
may be enrolled. Renal: 14. Creatinine <1.5 times normal OR creatinine
clearance >= 60 mL/min Prior therapeutics: 15. Toxicity from prior therapies
recovered to Grade <=1 or subject*s baseline, except for alopecia. In addition,
endocrinopathies associated with prior immunotherapy-based treatments that are
well controlled on replacement medication are not exclusionary. Chemotherapy
and targeted therapy: 16. At least 1 prior systemic cytotoxic or targeted
therapy regimen for LMS, which may include but is not limited to single-agent
doxorubicin or other anthracycline, doxorubicin plus ifosfamide, trabectin,
pazopanib, or gemcitabine with or without docetaxel Surgery: 17. At least 4
weeks since prior surgery and recovered in the opinion of investigator Other:
18. Capable of swallowing oral medication 19. Women of childbearing potential
(WOCBP; as defined by the Clinical Trials Facilitation and Coordination Group
[CTFG]) must have a negative serum pregnancy test at screening and agree to
abstinence or the use at least one of the following highly effective forms of
contraception (with a failure rate of <1% per year when used consistently
and correctly) (Clinical Trials Facilitation and Coordination Group 2020).
Contraception or abstinence must be continued for the duration of the study and
for at least 6 months after the last dose of study drug: • Combined (estrogen
and progestogen containing) hormonal contraception associated with inhibition
of ovulation: - Oral - Intravaginal - Transdermal • Progestogen-only hormonal
contraception associated with inhibition of ovulation: - Oral - Injectable -
Implantable • Intrauterine device • Intrauterine hormone-releasing system •
Bilateral tubal occlusion • Vasectomized partner with confirmed azoospermia All
females will be considered of childbearing potential unless they are
postmenopausal (at least 12 months consecutive amenorrhea in the appropriate
age group without oth
1. Received temozolomide or DTIC at any time 2. Any other systemic anticancer
therapy including investigational agents <=3 weeks before initiation of study
treatment. Additionally, subjects may not have received radiation <=3 weeks
before initiation of study treatment. 3. Known intolerance to DTIC or one or
more of the excipients in unesbulin. 4. Co-existing active infection or any
co-existing medical condition likely to interfere with study procedures,
including: a. Significant cardiovascular disease (New York Heart Association
Class III or IV cardiac disease), myocardial infarction within the past 6
months, unstable angina, congestive heart failure requiring therapy, unstable
arrhythmia or a need for antiarrhythmic therapy, or evidence of ischemia on
ECG, marked baseline prolongation of QT/QTc (corrected QT) interval, eg,
repeated demonstration of a QTc interval >500 msec (Long QT Syndrome
[congenital]) 5. Human immunodeficiency virus, hepatitis B virus, or hepatitis
C virus positivity 6. History of solid organ transplantation Therapeutics: 7.
Known or suspected allergy or immediate or delayed hypersensitivity to
unesbulin or DTIC, their excipients, or any agent given in this study
Gastrointestinal: 8. Bowel obstruction, malabsorption, or other
contraindication to oral medication 9. Gastrointestinal disease or other
conditions that could affect absorption. Active peptic ulcer disease, active
gastritis or previous history of gastric perforation within the last 2 years
10. Inflammatory bowel disease (including ulcerative colitis and Crohn*s
disease), diverticulitis, cholecystitis, symptomatic cholangitis, or
appendicitis Wounds/surgery: 11. Serious non-healing wound, ulcer, or bone
fractures 12. Major surgery, open biopsy, or significant traumatic injury that
has not recovered, in the opinion of the investigator, within 28 days of
baseline 13. Mucosal or internal bleeding Concomitant medications: 14.
Concomitant strong CYP1A2 inhibitors (such as fluoroquinolones [broad spectrum
quinolone antibiotics, including enoxacin and ciprofloxacin] and selective
serotonin reuptake inhibitor [SSRI] agents fluvoxamine and fluoxetine) should
be avoided on the same day that DTIC or unesbulin/placebo is administered.
CYP1A2 inhibitors may inhibit the conversion of DTIC to its active metabolite
and may increase the exposure of unesbulin. 15. Concomitant use of moderate
CYP1A2 inducers (such as phenytoin, rifampin, ritonavir, teriflunomide, and
barbiturates). Chronic use of marijuna should be avoided, but irregular use may
be permitted at the discretion of the treating investigator. CYP1A2 inducers
may increase the conversion of DTIC to its active metabolites. 16.
Coadministration of acid-reducing agents should be avoided approximately 4
hours before and after unesbulin/placebo administration. 17. Immunization with
a live vaccine within 30 days before starting study drug due to the risk of
serious and life-threatening infections Other: 18. Prior malignancies, other
than LMS, that required treatment or have shown evidence of recurrence (except
for non-melanoma skin cancer, adequately treated cervical carcinoma in situ,
prostate cancer in situ or any other low risk malignancy that is approved by
the medical monitor) during the 5 years before initiation. Cancer treated with
cura
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Endpoints:<br /><br>Primary:<br /><br>• PFS per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by<br /><br>an independent central imaging laboratory</p><br>
- Secondary Outcome Measures
Name Time Method