Trial Title:
A Study to Investigate Efficacy & Safety of Intratumoral INT230-6 Compared to US Standard of Care in Adults With Soft Tissue Sarcomas (INVINCIBLE-3)
NCT ID:
NCT06263231
Condition:
Sarcoma,Soft Tissue
Conditions: Official terms:
Sarcoma
Trabectedin
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
INT230-6
Description:
INT230-6 is a fixed combination of cisplatin, vinblastine and SHAO.
Arm group label:
INT230-6 Monotherapy
Intervention type:
Drug
Intervention name:
Eribulin
Description:
Eribulin IV
Arm group label:
US Standard of Care
Intervention type:
Drug
Intervention name:
Trabectedin
Description:
Trabectedin infusion
Arm group label:
US Standard of Care
Intervention type:
Drug
Intervention name:
Pazopanib
Description:
Pazopanib pill
Arm group label:
US Standard of Care
Summary:
To compare Overall Survival (OS) for INT230-6 vs United States (US) Standard of Care
(SOC) in participants with unresectable or metastatic liposarcoma, undifferentiated
pleomorphic sarcoma or leiomyosarcoma who have disease progression prior to study
enrollment following no more than 2 standard therapies, which must have included an
anthracycline-based regimen, unless contraindicated, and then a maximum of 1 additional
regimen.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Participant is of any sex and must be ≥ 18 years old and provide written informed
consent to participate in the study.
Type of Participant and Disease Characteristics
2. Histologically proven, unresectable, locally advanced, or metastatic Soft Tissue
Sarcoma (STS) only of the following subtypes: liposarcoma (dedifferentiated, myxoid,
round cell or pleomorphic), leiomyosarcoma, and undifferentiated pleomorphic
sarcoma. Participant must have a pathology report indicating the diagnosis of their
STS.
3. Participant must have received at least 1 line of therapy for a STS and must have
progressed following anthracycline-based or alternative standard therapies, except
if medically contraindicated or refused by participant. Participant cannot have
received more than 2 prior regiments for unresectable, locally advanced or
metastatic STS.
4. Participant must have measurable disease per RECIST 1.1 criteria.
5. Participant must have at least 1 target tumor suitable for injection using routine
image guidance ≥ 2 cm measurable by Computed Tomography (CT) or Magnetic Resonance
Imaging (MRI).
6. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance
status of 0, 1 or 2 (see Section 11.7).
7. Participant must have adequate organ function as defined by screening laboratory
values that must meet the following criteria:
1. Neutrophils ≥ 1500/μL (≥ 1.5× 109/L).
2. Prothrombin Time (PT), and International Normalized Ratio (INR) ≤ 1.5× Upper
Limit of Normal (ULN), platelets ≥ 100,000/μL (≥ 10× 109/L); hemoglobin ≥ 9
g/dL. Criteria must be met without erythropoietin dependency and without packed
red blood cell transfusion within the last 2 weeks.
3. Creatinine within normal range; or calculated creatinine clearance > 50 mL/min
by the Cockcroft-Gault equation.
4. Alanine Aminotransferase (ALT) Serum Glutamic-Oxaloacetic Transaminase (SGOT)/
Aspartate Aminotransferase (AST) Serum Glutamic-Pyruvic Transaminase (SGPT) ≤
2.5× ULN without, and ≤ 5× ULN with hepatic metastases.
5. Bilirubin ≤ 1.5× ULN (except participants with Gilbert's syndrome, who must
have total bilirubin < 3.0 mg/dL [< 52 µmol/L]).
6. Creatine phosphokinase < 2.5× ULN Sex and Contraceptive/Barrier Requirements
8. A female participant is eligible to participate if she is not pregnant (as
demonstrated by pregnancy testing prior to each treatment; performed at least
monthly), not breastfeeding, and at least 1 of the following conditions applies:
1. Not a Woman of Childbearing Potential (WOCBP). Women of non-childbearing
potential are defined as women with functioning ovaries with a documented
history of tubal ligation or hysterectomy or females who are post menopausal,
as defined by 12 months of spontaneous amenorrhea with an appropriate clinical
profile, e.g., age appropriate, > 45 years, in the absence of hormone
replacement therapy. In questionable cases, a blood sample for Follicle
Stimulating Hormone (FSH) and estradiol will be obtained to confirm
childbearing potential.
2. A WOCBP who may become pregnant or who is sexually active with a partner and
who could become pregnant agrees to use a highly effective form of
contraception during the study and for at least 7 months after the end of study
intervention (see Section 11.5.2 for highly effective methods of
contraception).
9. Male participants with female partners of childbearing potential must agree to use
contraception and refrain from sperm donation during the study and for 6 months
after the end of study intervention (Section 11.5.2.2).
Exclusion Criteria:
Informed Consent:
1. Adult participants who lack capacity to consent without a legally authorized
representative will be excluded from this study.
Medical Conditions:
2. Prior primary or metastatic brain or meningeal tumors unless clinically and
radiographically stable as well as off-steroid therapy for at least 2 months.
3. History of severe hypersensitivity reactions to US SOC agents and vinblastine or
cisplatin or other products of the same class and their excipients.
4. Histologically proven, unresectable, locally advanced or metastatic STS subtypes
other than those specified, for example excluded subtypes include liposarcoma (well
differentiated), desmoid or dermatofibrosarcoma protuberans.
5. Other prior malignancy, except for adequately treated basal or squamous cell skin
cancer or superficial bladder cancer, or any other cancer from which the participant
has been disease-free for at least 2 years.
6. Underlying medical condition that, in the investigator's opinion, will make the
administration of study intervention hazardous or obscure the interpretation of
toxicity determination or Adverse Events (AEs).
7. Concurrent medical condition requiring the use of immunosuppressive medications, or
systemic corticosteroids (topical steroids are permitted); systemic corticosteroids
must be discontinued at least 4 weeks prior to dosing.
Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be
continued if the participant is on a stable dose. Non-absorbed intra-articular
steroid injections will be permitted. Use of steroids as prophylactic treatment for
participants with contrast allergies to diagnostic imaging contrast dyes will be
permitted.
8. Participants who require uninterrupted anticoagulants of any type or is on daily
aspirin therapy or NSAIDS.
9. Known significant chronic liver disease, such as cirrhosis or active hepatitis
(potential participants who test positive for hepatitis B surface antigen or
hepatitis C antibodies are allowed provided they do not have active disease
requiring antiviral therapy).
10. Myocardial infarction within 6 months before enrollment, New York Heart Association
Class II or greater heart failure, uncontrolled angina, severe uncontrolled
ventricular arrhythmias, clinically significant pericardial disease or
electrocardiographic evidence of acute ischemic or active conduction system
abnormalities.
11. Uncontrolled intercurrent illness including, but not limited to, poorly controlled
hypertension or diabetes, ongoing active infection or psychiatric illness/social
situation that may potentially impair the participant's compliance with study
procedures.
12. Participants with a Corrected QT interval (QTc) of >450 ms for men and >470 ms for
women, or with a history of serum electrolyte abnormalities known to prolong the QT
interval such hypocalcemia, hypokalemia, and hypomagnesemia, or a family or personal
history of congenital long QT syndrome.
13. Participants actively receiving therapy with strong Cytochrome P450 3A4 isoenzyme
(CYP3A4) inhibitors (e.g, erythromycin, ketoconazole, itraconazole, voriconazole,
clarithromycin, telithromycin, ritonavir, mibefradil).
14. Participants actively receiving therapy with medications that have the potential to
prolong the QT interval and the treatment cannot be either discontinued or switched
to a different medication prior to starting study intervention.
Prior/Concomitant Therapy
15. Prior chemotherapy or immunotherapy (tumor vaccine, cytokine or growth factor given
to control the cancer: systemic or IT) must have been completed at least 4 weeks
prior to dosing (with the exception of kinase inhibitors or other short half-life
drugs, a 2-week washout is acceptable prior to treatment) and all AEs have either
returned to baseline or stabilized. Note: participants who have received prior
platinum therapy are eligible irrespective of their response. If participant had
received one of the 3 US SOC study regimens prior to enrollment, that previous US
SOC cannot be assigned in this study.
16. Prior systemic radiation therapy (IV, intrahepatic or oral) completed at least 4
weeks prior to study intervention administration. Prior focal radiotherapy completed
at least 2 weeks prior to study intervention administration.
a. Prior major treatment-related surgery completed at least 4 weeks prior to study
intervention administration.
17. Use of other investigational drugs (drugs not marketed for any indication) within 28
days prior to study intervention administration.
18. Received a live vaccine within 6 weeks of first dose of study intervention.
19. Received a Coronavirus Disease (COVID-19) vaccine less than 1 week prior to dosing
(Cycle 1/Day 1) and/or during the study received a COVID-19 vaccine or booster less
than 3 weeks ahead of a tumor assessment.
Other Exclusion Criteria
20. Pregnancy Exclusion: A WOCBP who has a positive pregnancy test (e.g., within 72
hours) prior to treatment. If a urine test is positive or cannot be confirmed as
negative, a serum pregnancy test will be required.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
USC/Norris Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Status:
Recruiting
Contact:
Last name:
James Hu, MD
Email:
Jameshu@med.usc.edu
Facility:
Name:
Sarcoma Oncology Center
Address:
City:
Santa Monica
Zip:
90403
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sant P Chawla, MD
Phone:
310-500-5391
Email:
Santchawla@gmail.com
Investigator:
Last name:
Sant P Chawla, MD
Email:
Principal Investigator
Facility:
Name:
University of California Los Angeles (UCLA) - Santa Monica Cancer Care
Address:
City:
Santa Monica
Zip:
90404
Country:
United States
Status:
Recruiting
Contact:
Last name:
Arun Singh, MD
Email:
Asingh@mednet.ucla.edu
Facility:
Name:
Nebraska Methodist Hospital
Address:
City:
Omaha
Zip:
68114
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kirsten M. Leu, MD
Email:
Kleu@nebraskacancer.com
Start date:
June 28, 2024
Completion date:
December 2028
Lead sponsor:
Agency:
Intensity Therapeutics, Inc.
Agency class:
Industry
Collaborator:
Agency:
Premier Research Group plc
Agency class:
Industry
Source:
Intensity Therapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06263231
