L19TNF + Doxorubicin for Metastatic Leiomyosarcoma
(FIBROSARC US Trial)
Recruiting in Palo Alto (17 mi)
+7 other locations
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Philogen S.p.A.
Must not be taking: Corticosteroids, Anticoagulants, others
Disqualifiers: Cardiac arrhythmias, Hypertension, others
No Placebo Group
Prior Safety Data
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?
The present study is an open-label, randomized, controlled, two-arm multi-center study of the efficacy of L19TNF treatment in combination with doxorubicin versus doxorubicin alone in metastatic leiomyosarcoma patients.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you require chronic corticosteroids, other immunosuppressants, or anticoagulants, and you should not use other anti-cancer treatments during the study.
What data supports the effectiveness of the drug L19TNF + Doxorubicin for treating metastatic leiomyosarcoma?
Doxorubicin is commonly used as a first-line treatment for leiomyosarcoma, but it is often not effective on its own. However, in other studies, doxorubicin has shown some activity against different types of cancer, such as malignant mesothelioma, when used in a modified form. This suggests that doxorubicin might have potential when combined with other treatments like L19TNF.12345
Is the combination of L19TNF and Doxorubicin safe for humans?
Doxorubicin is known to cause heart-related side effects, such as cardiotoxicity (damage to the heart muscle), which can be severe. Liposomal formulations of Doxorubicin may have lower risks of these side effects compared to conventional forms. There is no specific safety data available for L19TNF in combination with Doxorubicin.678910
What makes the drug L19TNF + Doxorubicin unique for treating metastatic leiomyosarcoma?
L19TNF + Doxorubicin is unique because it combines Doxorubicin, a standard first-line treatment for metastatic leiomyosarcoma, with L19TNF, which may enhance the drug's effectiveness by targeting tumor cells more precisely. This combination aims to improve outcomes by potentially increasing the drug's ability to attack cancer cells while minimizing side effects.13111213
Research Team
Scott Okuno, MD
Principal Investigator
Mayo Clinic, Rochester, MN
Eligibility Criteria
This trial is for adults and fully grown minors (16+) with stage IV high-grade leiomyosarcoma, a type of soft tissue sarcoma. Participants must have a life expectancy over 3 months, be HIV/HBV/HCV negative, not pregnant or breastfeeding, and willing to use effective contraception. They should not have had previous anthracycline chemo, certain heart conditions or severe diseases that could affect study participation.Inclusion Criteria
Life expectancy of at least 3 months in the judgment of the investigator
I have tested negative for HIV, hepatitis B, and C.
I am 16 or older and, if under 18, my growth plates have fused.
See 8 more
Exclusion Criteria
Abnormalities observed during baseline ECG and Echocardiogram investigations that are considered clinically significant by the investigator
My high blood pressure is not controlled, even with treatment.
Pregnancy or breast-feeding
See 19 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive doxorubicin or L19TNF plus doxorubicin in 21-day cycles
18 weeks
Every 3 weeks (in-person)
Maintenance
Participants continue treatment with monitoring every 12 weeks
54 weeks
Every 12 weeks (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 72 weeks
Every 12 weeks (in-person)
Treatment Details
Interventions
- Doxorubicin (Anti-tumor antibiotic)
- L19TNF (Monoclonal Antibodies)
Trial OverviewThe study compares the effectiveness of L19TNF in combination with doxorubicin versus doxorubicin alone in treating metastatic leiomyosarcoma. It's an open-label trial where patients are randomly assigned to one of two groups: one receiving the combined treatment and the other just doxorubicin.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm 2: L19TNF plus doxorubicinExperimental Treatment1 Intervention
Patients will receive a fixed dose of L19TNF in combination with a fixed dose doxorubicin.
Doxorubicin will be administered as a 15 ± 5 minutes i.v. infusion on day 1 of each 21-day cycle followed by at least 30 minutes pause before starting infusion of L19TNF.
Group II: Arm 1: DoxorubicinActive Control1 Intervention
Patients will receive a fixed dose doxorubicin, administered as a 15 ± 5 minutes i.v. infusion.
Doxorubicin is already approved in Canada, Japan for the following indications:
Approved in Canada as Doxorubicin for:
- Breast cancer
- Ovarian cancer
- Bladder cancer
- Lymphomas
- Leukemias
- Multiple myeloma
- Kaposi's sarcoma
- Soft tissue sarcomas
Approved in Japan as Doxorubicin for:
- Breast cancer
- Ovarian cancer
- Bladder cancer
- Lymphomas
- Leukemias
- Multiple myeloma
- Kaposi's sarcoma
- Soft tissue sarcomas
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Ohio State University Comprehensive Cancer CenterColumbus, OH
Rutgers Cancer Institute of New Jersey 195 Little Albany Street New Brunswick, NJ 08901 Room 2031New Brunswick, NJ
Seattle Cancer Care Alliance 825 Eastlake Ave. E. Seattle, WA 98109 Mail Stop CE2-128Seattle, WA
Mayo Clinic HospitalPhoenix, AZ
More Trial Locations
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Who Is Running the Clinical Trial?
Philogen S.p.A.
Lead Sponsor
Trials
42
Patients Recruited
2,400+
Findings from Research
In a study of 51 women with metastatic uterine leiomyosarcoma, the combination of fixed-dose rate gemcitabine and docetaxel as a second-line treatment showed an overall objective response rate of 27%, with a median duration of response lasting over 9 months.
The treatment was generally well-tolerated, with manageable side effects primarily involving myelosuppression, and a median progression-free survival of 5.6 months, indicating its potential effectiveness in this patient population.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Fixed-dose rate gemcitabine plus docetaxel as second-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II study.Hensley, ML., Blessing, JA., Degeest, K., et al.[2022]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Caelyx in malignant mesothelioma: a phase II EORTC study.Baas, P., van Meerbeeck, J., Groen, H., et al.[2020]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
A patient-derived orthotopic xenograft (PDOX) nude-mouse model precisely identifies effective and ineffective therapies for recurrent leiomyosarcoma.Zhang, Z., Hu, K., Kiyuna, T., et al.[2020]
In a phase II trial involving 40 women with recurrent Müllerian malignancies, the combination of liposomal doxorubicin and paclitaxel showed an overall objective response rate of 29%, with a higher response rate of 54% in patients whose tumors recurred at least 6 months after platinum-based therapy.
The combination treatment was associated with increased skin toxicity, specifically palmar plantar erythrodysesthesia, but did not affect the pharmacokinetics of paclitaxel, indicating that while effective, careful monitoring for side effects is necessary.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Phase II study of liposomal doxorubicin and weekly paclitaxel for recurrent Müllerian tumors.Campos, SM., Matulonis, UA., Penson, RT., et al.[2019]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Phase II study of mitomycin, doxorubicin, and cisplatin in the treatment of advanced uterine leiomyosarcoma: a Gynecologic Oncology Group study.Edmonson, JH., Blessing, JA., Cosin, JA., et al.[2019]
Probucol pretreatment significantly increased the clearance of doxorubicin (DOX) in plasma and altered its distribution in various tissues, suggesting it affects the pharmacokinetics of DOX.
Probucol also provided cardioprotection against DOX-induced toxicity by improving the ATP/ADP ratio and reducing markers of heart damage, indicating its potential as a protective agent during chemotherapy.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
New aspects in probucol cardioprotection against doxorubicin-induced cardiotoxicity.El-Demerdash, E., Ali, AA., Sayed-Ahmed, MM., et al.[2013]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Paeonol protects against doxorubicin-induced cardiotoxicity by promoting Mfn2-mediated mitochondrial fusion through activating the PKCε-Stat3 pathway.Ding, M., Shi, R., Fu, F., et al.[2023]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system.Fukuda, A., Tahara, K., Hane, Y., et al.[2022]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Recent progress in doxorubicin-induced cardiotoxicity and protective potential of natural products.Yu, J., Wang, C., Kong, Q., et al.[2018]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Cardioprotection by dexrazoxane in rats treated with doxorubicin and paclitaxel.Della Torre, P., Imondi, AR., Bernardi, C., et al.[2015]
In a phase II study involving 35 patients with advanced uterine leiomyosarcomas, liposomal doxorubicin showed limited efficacy, with only 1 complete response and 4 partial responses, indicating it may not be more effective than traditional doxorubicin.
The treatment was associated with significant toxicity, including grade 3 or 4 neutropenia in 16.1% of patients and gastrointestinal issues in several cases, highlighting the need for careful monitoring of side effects.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Phase II evaluation of liposomal doxorubicin (Doxil) in recurrent or advanced leiomyosarcoma of the uterus: a Gynecologic Oncology Group study.Sutton, G., Blessing, J., Hanjani, P., et al.[2022]
Liposomal formulations of anthracycline antibiotics, like Doxil and DaunoXome, improve the pharmacokinetics of these drugs, leading to longer circulation times and reduced toxicity compared to their free forms.
These liposomal formulations are effective in treating certain cancers, such as AIDS-related Kaposi's sarcoma, and their design allows for enhanced uptake by tumor cells when coupled with monoclonal antibodies.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
[Liposomal formulations of anthracycline antibiotics].Berezov, TT., Iaglova, NV., Chekhonin, VP., et al.[2014]
Anthracyclines, particularly doxorubicin (DOX), are highly effective antitumor drugs with a broad spectrum of activity against human cancers, although they can cause significant cardiotoxicity.
While several analogs of DOX have been developed to reduce toxicity and improve administration, none have demonstrated superior antitumor efficacy compared to DOX, which remains the most effective drug in this class despite ongoing efforts to mitigate its side effects.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
The anthracyclines: will we ever find a better doxorubicin?Weiss, RB.[2022]
References
Fixed-dose rate gemcitabine plus docetaxel as second-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II study. [2022]
Caelyx in malignant mesothelioma: a phase II EORTC study. [2020]
A patient-derived orthotopic xenograft (PDOX) nude-mouse model precisely identifies effective and ineffective therapies for recurrent leiomyosarcoma. [2020]
Phase II study of liposomal doxorubicin and weekly paclitaxel for recurrent Müllerian tumors. [2019]
Phase II study of mitomycin, doxorubicin, and cisplatin in the treatment of advanced uterine leiomyosarcoma: a Gynecologic Oncology Group study. [2019]
New aspects in probucol cardioprotection against doxorubicin-induced cardiotoxicity. [2013]
Paeonol protects against doxorubicin-induced cardiotoxicity by promoting Mfn2-mediated mitochondrial fusion through activating the PKCε-Stat3 pathway. [2023]
Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system. [2022]
Recent progress in doxorubicin-induced cardiotoxicity and protective potential of natural products. [2018]
Cardioprotection by dexrazoxane in rats treated with doxorubicin and paclitaxel. [2015]
Phase II evaluation of liposomal doxorubicin (Doxil) in recurrent or advanced leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. [2022]
[Liposomal formulations of anthracycline antibiotics]. [2014]
The anthracyclines: will we ever find a better doxorubicin? [2022]