Sarcoma,Soft TissuePhase 3INVINCIBLE-3NCT06263231
A Study to Investigate Efficacy & Safety of Intratumoral INT230-6 Compared to US Standard of Care in Adults With Soft Tissue Sarcomas (INVINCIBLE-3)
A Phase 3 study testing INT230-6, Eribulin and Trabectedin in people with Sarcoma,Soft Tissue, run by Intensity Therapeutics, Inc. at 17 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sarcoma,Soft Tissue
- What is being tested?
- INT230-6, Eribulin and Trabectedin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 333 participants
- Where
- 17 sitesin 5 countries
- Study dates
- 28 Jun 2024to Dec 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- 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.
- 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.
- 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 Computed Tomography (CT) or Magnetic Resonance Imaging (MRI).
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- Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (see Section 11.7).
- Participant must have adequate organ function as defined by screening laboratory values that must meet the following criteria:
- Neutrophils ≥ 1500/μL (≥ 1.5× 109/L).
- 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.
- Creatinine within normal range; or calculated creatinine clearance > 50 mL/min by the Cockcroft-Gault equation.
- 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.
- Bilirubin ≤ 1.5× ULN (except participants with Gilbert's syndrome, who must have total bilirubin < 3.0 mg/dL [< 52 µmol/L]).
- Creatine phosphokinase < 2.5× ULN Sex and Contraceptive/Barrier Requirements
- 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:
- 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.
- 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).
- 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).
Who cannot join
- Informed Consent:
- Adult participants who lack capacity to consent without a legally authorized representative will be excluded from this study.
- Medical Conditions:
- 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.
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- 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 Adverse Events (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.
- 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 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.
- 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/Concomitant Therapy
- 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.
- 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.
- 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 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
- 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.
Trial locations and contacts
17 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
17 sites in 5 countries
United States10 sites, 10 recruiting
- Recruiting
The James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210
David Liebner, MD, David.Liebner@osumc.edu
David Liebner, MD
- Recruiting
Duke Cancer Center
Durham, North Carolina, 27710
Richard Riedel, MD, 919-681-6932, richard.riedel@duke.edu
Richard Riedel, MD
- Recruiting
Profound Research LLC
Farmington Hills, Michigan, 48333
Ines Sampson, 248-477-0552, ines.sampson@profounresearch.io
Savitha Balaraman, MD
- Recruiting
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Sandy Tran, MD, 626-688-7013, Sandy.tran@med.usc.edu
James Hu, MD
- Recruiting
Yale School of Medicine - Smilow Cancer Hospital - Yale - New Haven Hospital Location
New Haven, Connecticut, 06519
Lauren King, 203-737-4635, lauren.king@yale.edu
Hari Deshpande, MD
- Recruiting
Nebraska Methodist Hospital
Omaha, Nebraska, 68114
Mary Beth Wilwerding, RN, 402-354-7939, marybeth.wilwerding@nebraskacancer.com
Kirsten M. Leu
- Recruiting
University of Pennsylvania - Abramson Cancer Center
Philadelphia, Pennsylvania, 19106
Oluseyi Ogunfidodo, MS, BSN, 215-829-7089, Oluseyi.ogunfidodo@pennmedicine.upenn.edu
Lee Hartner, MD
- Recruiting
Temple University - Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
David Brown, 215-728-2769, David.Brown2@fccc.edu
Margaret Von Mehren, MD
- Recruiting
Sarcoma Oncology Center
Santa Monica, California, 90403
Sant P Chawla, MD, 310-500-5391, Santchawla@gmail.com
Sant P Chawla, MD
- Recruiting
University of California Los Angeles (UCLA) - Santa Monica Cancer Care
Santa Monica, California, 90404
Jacqueline Banuelos-Murillo, 310-829-5471, JBanuelosMurillo@mednet.ucla.edu
Arun Singh, MD
Spain3 sites, 3 recruiting
- Recruiting
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
Romina Ribas, +34 935537116/7, RRibaas@santpau.cat
Raúl Terés Lleida, MD
- Recruiting
Hospital Universitari Vall Hebron
Barcelona, 08740
Claudia Valverde, MD, Cvalverde@vhio.net
Claudia Valverde, MD
- Recruiting
Centro Integral Oncologico Clara Campal (HM CIOCC)
Madrid, 28050
Elena Gonzalez, MD, +34917567850, egonzalezlopez@hmhospitales.com
Justo Ortega, MD
Germany2 sites, 2 recruiting
- Recruiting
Helios Klinikum Bad Saarow
Bad Saarow, 15526
Simone Micheel, +493363173728, simone.micheel@helios-gesundheit.de
Daniel Pink, MD
- Recruiting
Universitäres Krebszentrum (UCCL)
Leipzig, 04103
Claudia Schmidtchen, 0341 - 97 20037, Claudia.Schmidtchen@medizin.uni-leipzig.de
Anne-Marie Scheuble, MD
Canada1 site, 1 recruiting
- Recruiting
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
Gagan Sran, 16472898298, gagan.sran@uhnn.ca
Albiruni Abdul Razak, MD
France1 site, 1 recruiting
- Recruiting
Centre Leon Berard
Lyon, 69008
Patricia Dupont, MD, +33478782828, patricia.dupont@lyon.unicancer.fr
Jean-Yves Blay, MD
About this study
Official title: A Multicenter, Randomized, Phase 3 Study to Assess the Efficacy and Safety of INtratumorally Administered INT230-6 (SHAO, VINblastine, CIsplatin) Compared With US Standard of Care in Adults With Locally Recurrent, InoperaBLE, or Metastatic Soft Tissue Sarcomas (INVINCIBLE-3)
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.
- Conditions
- Sarcoma,Soft Tissue
- Being tested
- INT230-6, Eribulin, Trabectedin, Pazopanib
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INT230-6Drug
INT230-6 is a fixed combination of cisplatin, vinblastine and SHAO.
EribulinDrug
Eribulin IV
TrabectedinDrug
Trabectedin infusion
PazopanibDrug
Pazopanib pill
| Study group | Role | What they receive |
|---|---|---|
| INT230-6 Monotherapy | Experimental | INT230-6 administered intratumorally. Participants will be dosed every 2 weeks (± 2 days) for up to a total of 5 treatment sessions (e.g., Days 1, 15, 29, 43 and 57). Once the participant has completed the treatment phase, they will continue into a 22-month maintenance phase, where investigators may inject new lesions or previously injected lesions with up to 175 mL of INT230-6 every 12 weeks (Q12W) ± 14 days. Dose volume in a session is dependent on the participants presenting tumor burden. Receives: Drug: INT230-6 |
| US Standard of Care | Active comparator | Participants in this arm may receive any of the following depending on soft tissue sarcoma (STS) subtype and PI preference:
* Pazopanib: 800 mg PO every day until clinical deterioration or disease progression
* Trabectedin: 1.5 mg/m2 body surface area as 24-hour IV infusion every 3 weeks until clinical deterioration or disease progression
* Eribulin:
Non- European Union (EU) sites: 1.4 mg/m2 eribulin mesylate body surface area IV on Days 1 and 8 every 3 weeks until clinical deterioration or disease progression EU sites: 1.23 mg/m2 (free base) body surface area IV on Days 1 and 8 every 3 weeks until clinical deterioration or disease progression Receives: Drug: Eribulin; Drug: Trabectedin; Drug: Pazopanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
To compare OS for INT230-6 vs 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.
Measured: From date of randomization until the documented date of death from any cause for a period of up to 2 years, unless superiority is demonstrated sooner or 80% of deaths during the study period.
Secondary outcomes (2)
Overall Survival (OS) For INT230-6 Compared to OS for Standard of Care (SOC) for Participants with leiomyosarcoma
To compare OS for INT230-6 vs US SOC in participants with leiomyosarcoma
Measured: From date of randomization until the documented date of death from any cause for a period of up to 2 years, unless superiority is demonstrated sooner or 80% of deaths during the study period.
Overall Survival (OS) For INT230-6 Compared to OS for Standard of Care (SOC) for Participants with liposarcoma
To compare OS for INT230-6 vs US SOC in participants with liposarcoma
Measured: From date of randomization until the documented date of death from any cause for a period of up to 2 years, unless superiority is demonstrated sooner or 80% of deaths during the study period.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2024
- Study start28 Jun 2024
- Primary completionDec 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Sarcoma,Soft TissueStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 333 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Intensity Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Premier Research
- Responsible party
- Sponsor
- Investigators
- Christian F. Meyer, MD, PhD, MS, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06263231
- Sponsor's protocol ID
- IT-03
- Acronym
- INVINCIBLE-3
- Status last verified
- Aug 2026
- First submitted
- 1 Feb 2024
- Last updated
- 11 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: General Data Protection Regulation (GDPR) and HIPPA privacy laws will be followed for sharing of any data.
Publications
Billingsley KG, Burt ME, Jara E, Ginsberg RJ, Woodruff JM, Leung DH, Brennan MF. Pulmonary metastases from soft tissue sarcoma: analysis of patterns of diseases and postmetastasis survival. Ann Surg. 1999 May;229(5):602-10; discussion 610-2. doi: 10.1097/00000658-199905000-00002.
PubMed 10235518Beaver JA, Hazarika M, Mulkey F, Mushti S, Chen H, He K, Sridhara R, Goldberg KB, Chuk MK, Chi DC, Chang J, Barone A, Balasubramaniam S, Blumenthal GM, Keegan P, Pazdur R, Theoret MR. Patients with melanoma treated with an anti-PD-1 antibody beyond RECIST progression: a US Food and Drug Administration pooled analysis. Lancet Oncol. 2018 Feb;19(2):229-239. doi: 10.1016/S1470-2045(17)30846-X. Epub 2018 Jan 18.
PubMed 29361469Bender LH, Abbate F, Walters IB. Intratumoral Administration of a Novel Cytotoxic Formulation with Strong Tissue Dispersive Properties Regresses Tumor Growth and Elicits Systemic Adaptive Immunity in In Vivo Models. Int J Mol Sci. 2020 Jun 24;21(12):4493. doi: 10.3390/ijms21124493.
PubMed 32599852Bloom AC, Bender LH, Tiwary S, Pasquet L, Clark K, Jiang T, Xia Z, Morales-Kastresana A, Jones JC, Walters I, Terabe M, Berzofsky JA. Intratumorally delivered formulation, INT230-6, containing potent anticancer agents induces protective T cell immunity and memory. Oncoimmunology. 2019 Jul 16;8(10):e1625687. doi: 10.1080/2162402X.2019.1625687. eCollection 2019.
PubMed 31646070Cassier PA, Polivka V, Judson I, Soria JC, Penel N, Marsoni S, Verweij J, Schellens JH, Morales-Barrera R, Schoffski P, Voest EE, Gomez-Roca C, Evans TR, Plummer R, Gallerani E, Kaye SB, Olmos D. Outcome of patients with sarcoma and other mesenchymal tumours participating in phase I trials: a subset analysis of a European Phase I database. Ann Oncol. 2014 Jun;25(6):1222-8. doi: 10.1093/annonc/mdu108. Epub 2014 Mar 7.
PubMed 24608201Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014 Oct 5;740:364-78. doi: 10.1016/j.ejphar.2014.07.025. Epub 2014 Jul 21.
PubMed 25058905Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. doi: 10.1200/JCO.2015.62.4734. Epub 2015 Sep 14.
PubMed 26371143Gronchi A, Miah AB, Dei Tos AP, Abecassis N, Bajpai J, Bauer S, Biagini R, Bielack S, Blay JY, Bolle S, Bonvalot S, Boukovinas I, Bovee JVMG, Boye K, Brennan B, Brodowicz T, Buonadonna A, De Alava E, Del Muro XG, Dufresne A, Eriksson M, Fagioli F, Fedenko A, Ferraresi V, Ferrari A, Frezza AM, Gasperoni S, Gelderblom H, Gouin F, Grignani G, Haas R, Hassan AB, Hecker-Nolting S, Hindi N, Hohenberger P, Joensuu H, Jones RL, Jungels C, Jutte P, Kager L, Kasper B, Kawai A, Kopeckova K, Krakorova DA, Le Cesne A, Le Grange F, Legius E, Leithner A, Lopez-Pousa A, Martin-Broto J, Merimsky O, Messiou C, Mir O, Montemurro M, Morland B, Morosi C, Palmerini E, Pantaleo MA, Piana R, Piperno-Neumann S, Reichardt P, Rutkowski P, Safwat AA, Sangalli C, Sbaraglia M, Scheipl S, Schoffski P, Sleijfer S, Strauss D, Strauss S, Sundby Hall K, Trama A, Unk M, van de Sande MAJ, van der Graaf WTA, van Houdt WJ, Frebourg T, Casali PG, Stacchiotti S; ESMO Guidelines Committee, EURACAN and GENTURIS. Electronic address: clinicalguidelines@esmo.org. Soft tissue and visceral sarcomas: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up☆. Ann Oncol. 2021 Nov;32(11):1348-1365. doi: 10.1016/j.annonc.2021.07.006. Epub 2021 Jul 22. No abstract available.
PubMed 34303806Jones RL, Maki RG, Patel SR, Wang G, McGowan TA, Shalaby WS, Knoblauch RE, von Mehren M, Demetri GD. Safety and efficacy of trabectedin when administered in the inpatient versus outpatient setting: Clinical considerations for outpatient administration of trabectedin. Cancer. 2019 Dec 15;125(24):4435-4441. doi: 10.1002/cncr.32462. Epub 2019 Sep 10.
PubMed 31503332Lammers T, Peschke P, Kuhnlein R, Subr V, Ulbrich K, Huber P, Hennink W, Storm G. Effect of intratumoral injection on the biodistribution and the therapeutic potential of HPMA copolymer-based drug delivery systems. Neoplasia. 2006 Oct;8(10):788-95. doi: 10.1593/neo.06436.
PubMed 17032495Meyer M, Seetharam M. First-Line Therapy for Metastatic Soft Tissue Sarcoma. Curr Treat Options Oncol. 2019 Jan 24;20(1):6. doi: 10.1007/s11864-019-0606-9.
PubMed 30675651von Mehren M, Kane JM, Agulnik M, Bui MM, Carr-Ascher J, Choy E, Connelly M, Dry S, Ganjoo KN, Gonzalez RJ, Holder A, Homsi J, Keedy V, Kelly CM, Kim E, Liebner D, McCarter M, McGarry SV, Mesko NW, Meyer C, Pappo AS, Parkes AM, Petersen IA, Pollack SM, Poppe M, Riedel RF, Schuetze S, Shabason J, Sicklick JK, Spraker MB, Zimel M, Hang LE, Sundar H, Bergman MA. Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022 Jul;20(7):815-833. doi: 10.6004/jnccn.2022.0035.
PubMed 35830886Obeid M, Panaretakis T, Tesniere A, Joza N, Tufi R, Apetoh L, Ghiringhelli F, Zitvogel L, Kroemer G. Leveraging the immune system during chemotherapy: moving calreticulin to the cell surface converts apoptotic death from "silent" to immunogenic. Cancer Res. 2007 Sep 1;67(17):7941-4. doi: 10.1158/0008-5472.CAN-07-1622.
PubMed 17804698Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.
PubMed 7165009Padhani AR, Ollivier L. The RECIST (Response Evaluation Criteria in Solid Tumors) criteria: implications for diagnostic radiologists. Br J Radiol. 2001 Nov;74(887):983-6. doi: 10.1259/bjr.74.887.740983. No abstract available.
PubMed 11709461
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Phase 3 Study to Assess the Efficacy and Safety of INtratumorally Administered INT230-6 (SHAO, VINblastine, CIsplatin) Compared With US Standard of Care in Adults With Locally Recurrent, InoperaBLE, or Metastatic Soft Tissue Sarcomas (INVINCIBLE-3)
- ClinicalTrials.gov ID
- NCT06263231
- Acronym / sponsor ID
- INVINCIBLE-3 / IT-03
- Conditions
- Sarcoma,Soft Tissue
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 333 participants (estimated)
- Lead sponsor
- Intensity Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Premier Research
- Study start
- 28 Jun 2024 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 16 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| INT230-6 Monotherapy | Experimental | Drug: INT230-6INT230-6 administered intratumorally. Participants will be dosed every 2 weeks (± 2 days) for up to a total of 5 treatment sessions (e.g., Days 1, 15, 29, 43 and 57). Once the participant has completed the treatment phase, they will continue into a 22-month maintenance phase, where investigators may inject new lesions or previously injected lesions with up to 175 mL of INT230-6 every 12 weeks (Q12W) ± 14 days. Dose volume in a session is dependent on the participants presenting tumor burden. |
| US Standard of Care | Active comparator | Drug: Eribulin, Drug: Trabectedin, Drug: PazopanibParticipants in this arm may receive any of the following depending on soft tissue sarcoma (STS) subtype and PI preference: * Pazopanib: 800 mg PO every day until clinical deterioration or disease progression * Trabectedin: 1.5 mg/m2 body surface area as 24-hour IV infusion every 3 weeks until clinical deterioration or disease progression * Eribulin: Non- European Union (EU) sites: 1.4 mg/m2 eribulin mesylate body surface area IV on Days 1 and 8 every 3 weeks until clinical deterioration or disease progression EU sites: 1.23 mg/m2 (free base) body surface area IV on Days 1 and 8 every 3 weeks until clinical deterioration or disease progression |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
- 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.
- 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.
- Participant must have measurable disease per RECIST 1.1 criteria.
Key exclusion criteria (26 listed)
- Adult participants who lack capacity to consent without a legally authorized representative will be excluded from this study.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INT230-6INT230-6 is a fixed combination of cisplatin, vinblastine and SHAO. | Drug | INT230-6 Monotherapy |
| EribulinEribulin IV | Drug | US Standard of Care |
| TrabectedinTrabectedin infusion | Drug | US Standard of Care |
| PazopanibPazopanib pill | Drug | US Standard of Care |
Primary outcome
Overall Survival (OS)
Time frame: From date of randomization until the documented date of death from any cause for a period of up to 2 years, unless superiority is demonstrated sooner or 80% of deaths during the study period.
To compare OS for INT230-6 vs 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.
2 secondary outcomes
Overall Survival (OS) For INT230-6 Compared to OS for Standard of Care (SOC) for Participants with leiomyosarcoma
Time frame: From date of randomization until the documented date of death from any cause for a period of up to 2 years, unless superiority is demonstrated sooner or 80% of deaths during the study period.
Overall Survival (OS) For INT230-6 Compared to OS for Standard of Care (SOC) for Participants with liposarcoma
Time frame: From date of randomization until the documented date of death from any cause for a period of up to 2 years, unless superiority is demonstrated sooner or 80% of deaths during the study period.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2026.
- Background: PubMed 10235518Billingsley KG, Burt ME, Jara E, Ginsberg RJ, Woodruff JM, Leung DH, Brennan MF. Pulmonary metastases from soft tissue sarcoma: analysis of patterns of diseases and postmetastasis survival. Ann Surg. 1999 May;229(5):602-10; discussion 610-2. doi: 10.1097/00000658-199905000-00002.
- Background: PubMed 29361469Beaver JA, Hazarika M, Mulkey F, Mushti S, Chen H, He K, Sridhara R, Goldberg KB, Chuk MK, Chi DC, Chang J, Barone A, Balasubramaniam S, Blumenthal GM, Keegan P, Pazdur R, Theoret MR. Patients with melanoma treated with an anti-PD-1 antibody beyond RECIST progression: a US Food and Drug Administration pooled analysis. Lancet Oncol. 2018 Feb;19(2):229-239. doi: 10.1016/S1470-2045(17)30846-X. Epub 2018 Jan 18.
- Background: PubMed 32599852Bender LH, Abbate F, Walters IB. Intratumoral Administration of a Novel Cytotoxic Formulation with Strong Tissue Dispersive Properties Regresses Tumor Growth and Elicits Systemic Adaptive Immunity in In Vivo Models. Int J Mol Sci. 2020 Jun 24;21(12):4493. doi: 10.3390/ijms21124493.
- Background: PubMed 31646070Bloom AC, Bender LH, Tiwary S, Pasquet L, Clark K, Jiang T, Xia Z, Morales-Kastresana A, Jones JC, Walters I, Terabe M, Berzofsky JA. Intratumorally delivered formulation, INT230-6, containing potent anticancer agents induces protective T cell immunity and memory. Oncoimmunology. 2019 Jul 16;8(10):e1625687. doi: 10.1080/2162402X.2019.1625687. eCollection 2019.
- Background: PubMed 24608201Cassier PA, Polivka V, Judson I, Soria JC, Penel N, Marsoni S, Verweij J, Schellens JH, Morales-Barrera R, Schoffski P, Voest EE, Gomez-Roca C, Evans TR, Plummer R, Gallerani E, Kaye SB, Olmos D. Outcome of patients with sarcoma and other mesenchymal tumours participating in phase I trials: a subset analysis of a European Phase I database. Ann Oncol. 2014 Jun;25(6):1222-8. doi: 10.1093/annonc/mdu108. Epub 2014 Mar 7.
- Background: PubMed 25058905Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014 Oct 5;740:364-78. doi: 10.1016/j.ejphar.2014.07.025. Epub 2014 Jul 21.
- Background: PubMed 26371143Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. doi: 10.1200/JCO.2015.62.4734. Epub 2015 Sep 14.
- Background: PubMed 34303806Gronchi A, Miah AB, Dei Tos AP, Abecassis N, Bajpai J, Bauer S, Biagini R, Bielack S, Blay JY, Bolle S, Bonvalot S, Boukovinas I, Bovee JVMG, Boye K, Brennan B, Brodowicz T, Buonadonna A, De Alava E, Del Muro XG, Dufresne A, Eriksson M, Fagioli F, Fedenko A, Ferraresi V, Ferrari A, Frezza AM, Gasperoni S, Gelderblom H, Gouin F, Grignani G, Haas R, Hassan AB, Hecker-Nolting S, Hindi N, Hohenberger P, Joensuu H, Jones RL, Jungels C, Jutte P, Kager L, Kasper B, Kawai A, Kopeckova K, Krakorova DA, Le Cesne A, Le Grange F, Legius E, Leithner A, Lopez-Pousa A, Martin-Broto J, Merimsky O, Messiou C, Mir O, Montemurro M, Morland B, Morosi C, Palmerini E, Pantaleo MA, Piana R, Piperno-Neumann S, Reichardt P, Rutkowski P, Safwat AA, Sangalli C, Sbaraglia M, Scheipl S, Schoffski P, Sleijfer S, Strauss D, Strauss S, Sundby Hall K, Trama A, Unk M, van de Sande MAJ, van der Graaf WTA, van Houdt WJ, Frebourg T, Casali PG, Stacchiotti S; ESMO Guidelines Committee, EURACAN and GENTURIS. Electronic address: clinicalguidelines@esmo.org. Soft tissue and visceral sarcomas: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up☆. Ann Oncol. 2021 Nov;32(11):1348-1365. doi: 10.1016/j.annonc.2021.07.006. Epub 2021 Jul 22. No abstract available.
- Background: PubMed 31503332Jones RL, Maki RG, Patel SR, Wang G, McGowan TA, Shalaby WS, Knoblauch RE, von Mehren M, Demetri GD. Safety and efficacy of trabectedin when administered in the inpatient versus outpatient setting: Clinical considerations for outpatient administration of trabectedin. Cancer. 2019 Dec 15;125(24):4435-4441. doi: 10.1002/cncr.32462. Epub 2019 Sep 10.
- Background: PubMed 17032495Lammers T, Peschke P, Kuhnlein R, Subr V, Ulbrich K, Huber P, Hennink W, Storm G. Effect of intratumoral injection on the biodistribution and the therapeutic potential of HPMA copolymer-based drug delivery systems. Neoplasia. 2006 Oct;8(10):788-95. doi: 10.1593/neo.06436.
- Background: PubMed 30675651Meyer M, Seetharam M. First-Line Therapy for Metastatic Soft Tissue Sarcoma. Curr Treat Options Oncol. 2019 Jan 24;20(1):6. doi: 10.1007/s11864-019-0606-9.
- Background: PubMed 35830886von Mehren M, Kane JM, Agulnik M, Bui MM, Carr-Ascher J, Choy E, Connelly M, Dry S, Ganjoo KN, Gonzalez RJ, Holder A, Homsi J, Keedy V, Kelly CM, Kim E, Liebner D, McCarter M, McGarry SV, Mesko NW, Meyer C, Pappo AS, Parkes AM, Petersen IA, Pollack SM, Poppe M, Riedel RF, Schuetze S, Shabason J, Sicklick JK, Spraker MB, Zimel M, Hang LE, Sundar H, Bergman MA. Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022 Jul;20(7):815-833. doi: 10.6004/jnccn.2022.0035.
- Individual participant dataSharing planned: Yes. General Data Protection Regulation (GDPR) and HIPPA privacy laws will be followed for sharing of any data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christian F. Meyer, MD, PhD, MS principal investigator
Johns Hopkins University
17 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing INT230-6, Eribulin and Trabectedin in people with Sarcoma,Soft Tissue, run by Intensity Therapeutics, Inc. at 17 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Spain, Germany, Canada, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kimberly Guedes, RN, M.B.A ((203) 293-4224, KGuedes@intensitytherapeutics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: From date of randomization until the documented date of death from any cause for a period of up to 2 years, unless superiority is demonstrated sooner or 80% of deaths during the study period.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06263231, which also lists 21 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026.