Neoplasms

All Conditions

Rare Diseases

Leiomyosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Avelumab

Antimetabolites

Antineoplastic Agents, Immunological

* Avelumab: 10 mg/kg by IV infusion over 1 hour, every 2 weeks
* Gemcitabine: 1000 mg/m2 by IV infusion over 30 minutes on Days 1, 8, and 15 of each 28-day cycle

Avelumab and Gemcitabine

Young Saing Kim, MD, PhD

Sung Yong Oh

Young Saing Kim, MD

Yu Jung Kim

Jeong-eun Kim

Jeeyun Lee

Mi So Kim

A Phase 2 trial of avelumab plus gemcitabine in advanced leiomyosarcoma as a second line treatment

Avelumab in Combination With Gemcitabine in Advanced Leiomyosarcoma as a Second-line Treatment

Phase II Trial of Avelumab in Combination With Gemcitabine in Advanced Leiomyosarcoma as a Second-line Treatment

Merck KGaA, Darmstadt, Germany

Chong Kun Dang Pharmaceutical Corp.

Gachon University Gil Medical Center

Associate Professor

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

The phase 1b trial will follow a standard 3+3 design. Upon determination of the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of lurbinectedin plus doxorubicin. A treatment cycle will be defined as 21 consecutive days. Treatment will be administered on an outpatient basis

* Lurbinectedin
* Doxorubicin

The randomized two arm phase 2 trial will begin following the determination of the RP2D for lurbinectedin and doxorubicin.

* Participants will be randomized 1:1 to enroll to either Arm 1 or Arm 2
* Participants enrolled to Arm 1 will receive Lurbinectedin with Doxorubicin at the RP2D defined during the phase 1b portion of the trial.

The randomized two arm phase 2 trial will begin following the determination of the RP2D for lurbinectedin and doxorubicin.

* Participants will be randomized 1:1 to enroll to either Arm 1 or Arm 2
* Participants enrolled to Arm 2 will receive Doxorubicin at the standard dose of 75 mg/m2

Dosage per protocol, escalation per protocol, IV over 60 minutes (± 5 minute infusion window), schedule per protocol

Lurbinectedin

Dosage per protocol, IV per institutional standards of practice and the FDA package insert, schedule per protocol

Gregory Cote, M.D. Ph.D

Mahesh Seetharam, MD

Steven Attia, DO

Gregory Cote, MD, Ph.D

Suzanne George, MD

Brittany Siontis, MD

Sujana Movva, MD

This research study involves the study drug lurbinectedin in combination with doxorubicin.

This research has two parts. The first part is being done to determine the tolerability of lurbinectedin with doxorubicin in people with soft tissue sarcoma. The second part is a randomized study to determine which is more effective at treating leiomyosarcoma, lurbinectedin with doxorubicin or lurbinectedin alone.

This is an open label phase 1b/2 study exploring the safety and efficacy of lurbinectedin with doxorubicin.

- The phase 1b trial will follow a standard 3+3 design. Upon determination of the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of lurbinectedin plus doxorubicin, the randomized phase 2 trial in participants with advanced leiomyosarcoma (LMS) will commence. Participants will be randomized 1:1 for enrollment to one of two treatment arms:

* Arm 1: Lurbinectedin with Doxorubicin
* Arm 2: Doxorubicin Monotherapy

This is a Phase Ib/II clinical trial. A Phase Ib clinical trial tests the safety of an investigational drug combination and also tries to define the appropriate dose of the investigational drugs to use for further studies. "Investigational" means that the drugs are being studied.

The U.S. Food and Drug Administration (FDA) has not approved lurbinectedin for this specific disease but it has been approved for the treatment of small cell lung cancer.

The U.S. FDA has approved doxorubicin as a treatment option for soft-tissue sarcoma.

Lurbinectedin is a synthetically derived chemical that binds to DNA. The binding to DNA likely induces cell death. Doxorubicin is a cytotoxic chemotherapy drug that kills cancer cells by several mechanisms including binding to DNA.

Lurbinectedin + Doxorubicin In Leiomyosarcoma

A Phase 1b/2 Trial of Lurbinectedin Plus Doxorubicin in Leiomyosarcoma

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

The MTD will be defined as the dose where less than 1 in 3 patients experience a DLT. At least 6 patients must be treated at this dose level. DLTs will be defined as toxicities experienced by participants enrolled to the phase 1b portion of the trial that are considered at least possibly related to the treatment regimen, occur during the first cycle of treatment.

Progression-Free Survival (PFS) is defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.

Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria

PFS is defined as the time from as the time from randomization (or registration) to the earlier of progression or death due to any cause, whichever occurs first

OS is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive.

NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Avelumab in Combination With Gemcitabine in Advanced Leiomyosarcoma as a Second-line Treatment	NCT03536780	Leiomyosarcoma ...	Avelumab and Ge...	20 Years -	Gachon University Gil Medical Center
Avelumab in Combination With Gemcitabine in Advanced Leiomyosarcoma as a Second-line Treatment	NCT03536780	Leiomyosarcoma ...	Avelumab and Ge...	20 Years -	Gachon University Gil Medical Center
Lurbinectedin + Doxorubicin In Leiomyosarcoma	NCT05099666	Advanced Soft-t... Metastatic Soft... Advanced Leiomy... Leiomyosarcoma ...	Lurbinectedin Doxorubicin	18 Years -	Massachusetts General Hospital

Spots Global Cancer Trial Database for leiomyosarcoma metastatic