A Phase 3 Multicenter Randomized Study Comparing INT230-6 (Vinblastine Sulfate, Cisplatin) to Standard Care in Adults with Metastatic Soft Tissue Sarcomas
- Trial ID
- 2024-512423-36-00
- Protocol
- IT-03
- Sponsor
- Intensity Therapeutics Inc.
Trial statistics
Objectives
The primary objective of this study is to compare **overall survival (OS)** for INT230-6 versus the US standard of care (SOC) in participants with unresectable or metastatic liposarcoma, undifferentiated pleomorphic sarcoma, or leiomyosarcoma. This objective is clinically relevant as it aims to determine the efficacy of INT230-6 in improving survival outcomes in patients with these aggressive and difficult-to-treat soft tissue sarcomas.
Secondary objectives include:
- Comparing OS for INT230-6 versus US SOC in participants specifically with leiomyosarcoma.
- Comparing OS for INT230-6 versus US SOC in participants specifically with liposarcoma.
- Exploratory: Comparing the incidence of grade 3 or higher drug-related adverse events (AEs) of INT230-6 versus US SOC in participants with advanced soft tissue sarcoma (aSTS).
- Exploratory: Comparing the quality of life (QoL) using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30) for INT230-6 versus US SOC in participants with aSTS.
- Exploratory: Comparing health parameters.
Participants
The clinical trial involves a total of **215 participants** diagnosed with unresectable or metastatic **liposarcoma**, **undifferentiated pleomorphic sarcoma**, or **leiomyosarcoma**. The study population includes both male and female participants aged 18 years and older. Participants were selected based on their ability to provide informed consent and their diagnosis of specific subtypes of soft tissue sarcoma (STS), confirmed through histological evidence. The trial includes individuals who have previously undergone at least one line of therapy for advanced STS and have shown disease progression following standard treatments. Participants must have measurable disease according to RECIST 1.1 criteria and meet specific health criteria, including adequate organ function and an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Lifestyle considerations such as diet and physical activity are not specified, but participants must adhere to contraception requirements if applicable. The trial does not exclude based on gender, and both vulnerable and non-vulnerable populations are included. The sponsor has not provided additional information regarding specific lifestyle factors or habits of the participants.
Plans and Procedures
The clinical trial is designed as a **randomized**, double-blind, controlled study to evaluate the efficacy and safety of intratumorally administered INT230-6 compared with the US standard of care in adult participants with locally recurrent, inoperable, or metastatic soft tissue sarcomas. The trial will span an estimated duration until December 31, 2027, with recruitment starting on September 2, 2024. Participants will be involved in the study for a maximum treatment period of 24 months. The study will include several key visits: an initial **screening** visit to assess eligibility based on inclusion criteria such as age, histologically proven sarcoma subtypes, and adequate organ function; regular follow-up visits to monitor treatment response and safety; and an end-of-study visit to evaluate overall outcomes.
Participants will be randomly assigned to receive either the investigational product INT230-6, which contains **vinblastine sulfate** and **cisplatin**, or the standard of care. The investigational product will be administered via intratumoral injection, while the standard of care may involve intravenous injection, infusion, or oral administration of comparator drugs such as **eribulin**, **trabectedin**, or **pazopanib**. The primary endpoint of the study is overall survival, defined as the time from randomization to death from any cause. Secondary endpoints include the incidence of grade 3 or higher drug-related adverse events and changes in quality of life scores.
Participants are expected to comply with study requirements, including the use of effective contraception for those of childbearing potential. Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or adverse events that compromise participant safety. The trial aims to provide comprehensive data on the comparative effectiveness of INT230-6 in treating specific subtypes of soft tissue sarcomas, contributing to the advancement of therapeutic options for these rare diseases.
Treatment
The clinical trial involves the administration of **HALAVEN** 0.44 mg/ml solution for injection, which contains the active substance **eribulin**. This pharmaceutical form is a solution for injection, administered via **intravenous injection**. The maximum daily dose is 1.23 mg/m², with a total treatment period of up to 24 weeks. The product is manufactured by EISAI GMBH and is not a pediatric formulation. Participant compliance will be monitored through regular assessments of dosing adherence and administration records.
Another treatment in the trial is **Trabectedin EVER Pharma**, a 1 mg powder for concentrate for solution for infusion, containing the active substance **trabectedin**. This medication is administered through **intravenous infusion**. The maximum daily dose is 1.5 mg/m², with a treatment duration of up to 24 weeks. The product is provided by EVER VALINJECT GMBH and is also not intended for pediatric use. Compliance monitoring will include infusion records and participant follow-up visits.
The experimental medication **INT230-6** is a solution for injection containing the active substances **vinblastine sulfate** and **cisplatin**. It is administered via **intratumoral use**. The maximum daily dose is 175 ml, with a treatment period of up to 24 weeks. This product is developed by INTENSITY THERAPEUTICS, INC. Compliance will be ensured through direct observation of administration and documentation of dosing schedules.
Additionally, **Pazopanib PharOS** 200 mg film-coated tablets are used as a comparator treatment. The active substance is **pazopanib**, and the medication is administered **orally**. The maximum daily dose is 800 mg, with a treatment period of up to 24 weeks. This product is manufactured by PHAROS - PHARMACEUTICAL ORIENTED SERVICES LIMITED. Participant adherence will be monitored through pill counts and patient diaries.
Efficacy
The efficacy of the clinical trial will be assessed primarily through the measurement of **Overall Survival (OS)**, defined as the time from the date of randomization to the date of death due to any cause. This primary endpoint will provide a direct measure of the treatment's impact on survival in participants with locally recurrent, inoperable, or metastatic soft tissue sarcomas. Secondary endpoints include exploratory assessments such as the incidence of grade 3 or higher drug-related adverse events, changes from baseline in the global health status/quality of life (QoL) scale score of the EORTC QLQ-C30, and time to a 10% definitive deterioration in the global health status/QoL scale score. These exploratory endpoints will be evaluated up to 24 months and will involve a summary of composite measures of change from baseline in domain scores, health states, overall health status, and index values at each assessment. Changes in safety parameters, including laboratory test results and ECOG performance status, will also be monitored. The trial is designed to compare the efficacy of intratumorally administered INT230-6 with the US standard of care in adult participants, with the estimated end date set for December 31, 2027.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant is of any sex and must be ≥ 18 years old and provide written informed consent to participate in the study, or consent may be provided by the participant’s legally acceptable representative (In Germany: participants must be able to provide consent to participation; legal representatives are not allowed)
- Histologically proven, unresectable, locally advanced, or metastatic STS only of the following subtypes: liposarcoma (dedifferentiated, myxoid, round cell or pleomorphic), leiomyosarcoma (non-uterine), and undifferentiated pleomorphic sarcoma. Participant must have a pathology report indicating the diagnosis of their STS.
- Participant must have received at least 1 line of therapy for aSTS 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
- Participant must have measurable disease per RECIST 1.1 criteria
- Participant must have at least 1 target tumor suitable for injection using routine image guidance ≥ 2 cm measurable by CT or MRI.
- Participant must have an ECOG performance status of 0, 1 or 2
- Participant must have adequate organ function as defined by screening laboratory values that must meet the following criteria: a. Neutrophils ≥ 1500/μL (≥ 1.5× 1000000000/L). b. PT, and INR ≤ 1.5× ULN, platelets ≥ 100,000/μL (≥ 10× 1000000000/L); hemoglobin ≥ 9 g/dL. Criteria must be met without erythropoietin dependency and without packed red blood cell transfusion within the last 2 weeks. c. Creatinine within normal range; or calculated creatinine clearance > 50 mL/min by the Cockcroft-Gault equation. d. ALT SGOT/ AST SGPT ≤ 2.5× ULN without, and ≤ 5× ULN with hepatic metastases. e. Bilirubin ≤ 1.5× ULN (except participants with Gilbert’s syndrome, who must have total bilirubin < 3.0 mg/dL [< 52 μmol/L]). f. Creatine phosphokinase < 2.5× ULN
- 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: a. Not a 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 FSH and estradiol will be obtained to confirm childbearing potential. b. 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
- 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
- Participant (or legally acceptable representative if applicable) is capable of giving signed informed consent and provides written informed consent for the study as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Exclusion Criteria
- Prior primary or metastatic brain or meningeal tumors unless clinically and radiographically stable as well as off-steroid therapy for at least 2 months.
- History of severe hypersensitivity reactions to US SOC agents and vinblastine or cisplatin or other products of the same class and their excipients.
- 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.
- 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.
- 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 AEs.
- 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.
- Use of other investigational drugs (drugs not marketed for any indication) must be discontinued at least 28 days prior to study intervention administration.
- Participants who require uninterrupted anticoagulants of any type or is on daily aspirin therapy or NSAIDS.
- 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).
- 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.
- 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.
- Participants with a 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.
- Participants actively receiving therapy with strong Cytochrome P450 3A4 isoenzyme (CYP3A4) inhibitors (e.g, erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil).
- 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 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 1 of the 3 US SOC study regimens prior to enrollment, that previous US SOC cannot be assigned in this study.
- 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.
- Use of other investigational drugs (drugs not marketed for any indication) within 28 days prior to study intervention administration.
- Received a live vaccine within 6 weeks of first dose of study intervention.
- Received a 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.
- Pregnancy Exclusion: A WOCBP who has a positive serum pregnancy test at the clinical visit, prior to treatment. If a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Yet Recruiting | 02 Sept 2024 | 26 |
 Germany | Not Yet Recruiting | 02 Sept 2024 | 27 |
 Italy | Not Yet Recruiting | 02 Sept 2024 | 22 |
 Poland | Not Yet Recruiting | 02 Sept 2024 | 18 |
 Spain | Not Yet Recruiting | 02 Sept 2024 | 25 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Trabectedin EVER Pharma 1 mg Pulver für ein Konzentrat zur Herstellung einer Infusionslösung | Comparator | PULVER FÜR EIN KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | INTRAVENIOUS INFUSION | 1.5 | 24 | PRD10371516 |
HALAVEN 0.44 mg/ml solution for injection | Comparator | SOLUTION FOR INJECTION | INTRAVENOUS INJECTION | 1.23 | 24 | PRD3616234 |
Pazopanib PharOS 200 mg film-coated tablets | Comparator | FILM-COATED TABLETS | ORAL | 800 | 24 | PRD9404128 |