114 Participants Needed

L19TNF + Doxorubicin for Metastatic Leiomyosarcoma

(FIBROSARC US Trial)

Recruiting at 7 trial locations
TH
SB
MS
Overseen ByMahesh Seetharam, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 4 JurisdictionsThis treatment is already approved in other countries

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 H. Okuno, M.D. - Doctors and ...

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

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
  • L19TNF
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 United States, European Union, Canada, Japan for the following indications:

🇺🇸
Approved in United States as Adriamycin for:
  • Breast cancer
  • Ovarian cancer
  • Bladder cancer
  • Lymphomas
  • Leukemias
  • Multiple myeloma
  • Kaposi's sarcoma
  • Soft tissue sarcomas
🇪🇺
Approved in European Union as Doxorubicin for:
  • Breast cancer
  • Ovarian cancer
  • Bladder cancer
  • Lymphomas
  • Leukemias
  • Multiple myeloma
  • Kaposi's sarcoma
  • Soft tissue sarcomas
🇨🇦
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

Who Is Running the Clinical Trial?

Philogen S.p.A.

Lead Sponsor

Trials
42
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.
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]
In a phase II study involving 33 patients with malignant pleural mesothelioma, Caelyx (a liposomal form of doxorubicin) was found to be well tolerated, with mild toxicity primarily manifesting as palmar plantar erythrodysesthesia in 62% of patients.
Despite being well tolerated, Caelyx showed limited efficacy, with only 6% of patients achieving a partial response and a median survival of 13 months, indicating that it may not be a promising single-agent treatment for chemotherapy-naive mesothelioma patients.
Caelyx in malignant mesothelioma: a phase II EORTC study.Baas, P., van Meerbeeck, J., Groen, H., et al.[2020]
The patient-derived orthotopic xenograft (PDOX) mouse model was developed to test treatments for leiomyosarcoma, a rare and difficult-to-treat cancer, using a tumor from a patient's thigh.
In this study, the combination of gemcitabine and docetaxel, trabectedin, and temozolomide were found to be highly effective against leiomyosarcoma, while the commonly used first-line treatment, doxorubicin, was ineffective, highlighting the PDOX model's ability to identify effective therapies.
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]

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]
11.United Statespubmed.ncbi.nlm.nih.gov
Phase II evaluation of liposomal doxorubicin (Doxil) in recurrent or advanced leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. [2022]
12.Russia (Federation)pubmed.ncbi.nlm.nih.gov
[Liposomal formulations of anthracycline antibiotics]. [2014]
13.United Statespubmed.ncbi.nlm.nih.gov
The anthracyclines: will we ever find a better doxorubicin? [2022]