Lurbinectedin + Doxorubicin for Leiomyosarcoma

(SaLuDo Trial)

Recruiting in Palo Alto (17 mi)

+79 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: PharmaMar

Must not be taking: Anthracyclines, Lurbinectedin, Trabectedin

Disqualifiers: Cardiac disease, Immunodeficiency, Hepatitis, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The primary objective of this phase IIb/III study is to evaluate whether the combination of lurbinectedin plus doxorubicin given as first line treatment for metastatic leiomyosarcoma (LMS) prolongs the progression-free survival (PFS) by Independent Review Committee (IRC) when compared to doxorubicin administered as a single agent.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you must not use strong or moderate inhibitors or strong inducers of CYP3A4 activity within two weeks before starting the trial. There is also a required washout period of at least three weeks since your last systemic treatment.

Is the combination of Lurbinectedin and Doxorubicin safe for humans?

Doxorubicin, a component of the treatment, is known to cause heart-related side effects, but there are formulations like Myocet® and Doxil® that are designed to be less harmful to the heart. Common side effects include low white blood cell counts and eye-related issues, but these often resolve quickly after stopping the drug. ^{1 2 3 4 5}

What makes the drug combination of Lurbinectedin and Doxorubicin unique for treating leiomyosarcoma?

The combination of Lurbinectedin and Doxorubicin is unique because it has shown a 35% objective response rate in leiomyosarcoma, which is promising compared to typical chemotherapy response rates of 20-40% in soft tissue sarcomas. Lurbinectedin is a new anticancer agent that works by inhibiting oncogenic transcription, and when combined with Doxorubicin, it has demonstrated synergistic antitumor activity. ^{6 7 8 9 10}

Research Team

Eligibility Criteria

Adults with metastatic Leiomyosarcoma who haven't had systemic therapy for their metastasis can join. They should have good organ function, no history of certain heart diseases or infections like HIV, and not be on drugs that affect liver enzymes. Women must not be pregnant and participants must use effective contraception.

Inclusion Criteria

I haven't had systemic therapy or anthracyclines for my metastatic disease.

It has been over two weeks since my last radiation treatment.

You have a hemoglobin level of 9.0 or higher, an ANC above 2.0 x 10^9/L, and a platelet count greater than 100 x 109/L (after any RBC transfusions).

Exclusion Criteria

I have previously been treated with anthracyclines, lurbinectedin, or trabectedin.

I have an infection that is not under control.

I had cancer before, but it was either skin cancer, cervical, breast, or superficial bladder cancer and was cured over 3 years ago.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive doxorubicin and lurbinectedin intravenously every three weeks on day 1 of each treatment cycle

9-12 weeks

3-4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Doxorubicin (Anti-tumor antibiotic)
• Lurbinectedin (Other)

Trial Overview The trial is testing if adding Lurbinectedin to Doxorubicin improves the time patients live without their cancer getting worse compared to using Doxorubicin alone. It's a phase IIb/III study where one group gets both drugs and another only gets Doxorubicin.

Participant Groups

Group I: Phase IIb (& Phase III if selected), Doxorubicin (dose C) + Lurbinectedin (dose D) Experimental Treatment 2 Interventions

Participants will receive doxorubicin intravenously q3wk on day 1 of each treatment cycle (treatment cycle = three weeks).

Group II: Phase IIb (& Phase III if selected), Doxorubicin (dose A) + Lurbinectedin (dose B) Experimental Treatment 2 Interventions

Participants will receive doxorubicin and lurbinectedin intravenously every three weeks (q3wk) on day 1 of each treatment cycle (treatment cycle = three weeks).

Group III: Phase IIb & Phase III, Doxorubicin Active Control 1 Intervention

Participants will receive doxorubicin intravenously q3wk on day 1 of each treatment cycle (treatment cycle = three weeks).

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 Nearby Select from list below to view details:

University of Pennsylvania Abramson Cancer Center Philadelphia, PA

Mayo Clinic Hospital - Phoenix Phoenix, AZ

Mayo Clinic - Jacksonville Jacksonville, FL

University of Michigan Ann Arbor, MI

More Trial Locations

Who Is Running the Clinical Trial?

PharmaMar

Lead Sponsor

Trials

93

Patients Recruited

11,800+

Findings from Research

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

Ocular adverse reactions associated with adriamycin (doxorubicin). Curran, CF., Luce, JK.[2019]

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]

Myocet®, a non-pegylated liposome-encapsulated form of doxorubicin, is designed to enhance the effectiveness of doxorubicin while reducing its cardiotoxicity, making it a safer option for breast cancer and other tumors.

Clinical evidence indicates that Myocet® has a lower incidence of hematological toxicity compared to conventional doxorubicin, and it effectively reduces the severity of cardiac events associated with treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Non-pegylated doxorubicin (Myocet®) as the less cardiotoxic alternative of free doxorubicin]. Nagykálnai, T.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticancer and cardio-protective effects of liposomal doxorubicin in the treatment of breast cancer. Franco, YL., Vaidya, TR., Ait-Oudhia, S.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II multi-strata study of lurbinectedin as a single agent or in combination with conventional chemotherapy in metastatic and/or unresectable sarcomas. Cote, GM., Choy, E., Chen, T., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxorubicin plus lurbinectedin in patients with advanced endometrial cancer: results from an expanded phase I study. Kristeleit, R., Moreno, V., Boni, V., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A model-based head-to-head comparison of single-agent lurbinectedin in the pivotal ATLANTIS Study. Fudio, S., Pérez-Ramos, L., Asín-Prieto, E., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of lurbinectedin (PM01183) and doxorubicin in relapsed small-cell lung cancer: results from a phase I study. Calvo, E., Moreno, V., Flynn, M., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human phase I study of Lurbinectedin (PM01183) in patients with advanced solid tumors. Elez, ME., Tabernero, J., Geary, D., et al.[2022]

References

1. Egypt pubmed.ncbi.nlm.nih.gov

Paeonol protects against doxorubicin-induced cardiotoxicity by promoting Mfn2-mediated mitochondrial fusion through activating the PKCε-Stat3 pathway. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Ocular adverse reactions associated with adriamycin (doxorubicin). [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Cardioprotection by dexrazoxane in rats treated with doxorubicin and paclitaxel. [2015]

4. Hungary pubmed.ncbi.nlm.nih.gov

[Non-pegylated doxorubicin (Myocet®) as the less cardiotoxic alternative of free doxorubicin]. [2018]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Anticancer and cardio-protective effects of liposomal doxorubicin in the treatment of breast cancer. [2020]

6. England pubmed.ncbi.nlm.nih.gov

A phase II multi-strata study of lurbinectedin as a single agent or in combination with conventional chemotherapy in metastatic and/or unresectable sarcomas. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Doxorubicin plus lurbinectedin in patients with advanced endometrial cancer: results from an expanded phase I study. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

A model-based head-to-head comparison of single-agent lurbinectedin in the pivotal ATLANTIS Study. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of lurbinectedin (PM01183) and doxorubicin in relapsed small-cell lung cancer: results from a phase I study. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

First-in-human phase I study of Lurbinectedin (PM01183) in patients with advanced solid tumors. [2022]