Neoplasms

All Conditions

Rare Diseases

Sarcoma

Leiomyosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

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

Jazz Pharmaceuticals

Massachusetts General Hospital

Principal Investigator

Symptoms and General Pathology

Recurrence

Trabectedin

Olaratumab

Antineoplastic Agents, Alkylating

Alkylating Agents

Trabectedin \[T\], Doxorubicin \[D\], and Olaratumab \[O\]

Administered intravenously per protocol on Day 1 for 21-day cycles.

Marilyn Huang, MD, MS

This study seeks to determine if addition of trabectedin (T) to combination doxorubicin (D) and olaratumab (O), is feasible and tolerable with antitumor activity in metastatic or recurrent Leiomyosarcomas (LMS) patients who have limited therapeutic options.

This is a traditional 3+3 phase I trial design to identify the recommended phase II dose (RP2D) of Trabectedin \[T\] that can be used in combination with Doxorubicin \[D\] and Olaratumab \[O\] for the treatment of patients with advanced stage or recurrent LMS.

Patients will be treated at an assigned dose level of combination therapy per dose escalation design.

Trabectedin, Doxorubicin and Olaratumab in Patients With Metastatic or Recurrent Leiomyosarcoma

A Phase I Study of Trabectedin in Combination With Fixed Doses of Doxorubicin and Olaratumab in Patients With Metastatic or Recurrent Leiomyosarcoma

Determination of the recommended phase 2 dose (RP2D) of Trabectedin \[T\] to be used in combination with Doxorubicin \[D\] and Olaratumab \[O\] for the treatment of patients with metastatic or recurrent LMS. Patients will be treated at one of 4-6 dose levels according to the standard dose escalation/de-escalation scheme. In accordance with this scheme, the RP2D of TDO will be established as the highest dose level tested for which no more than 2 out of 12 patients experiences dose-limiting toxicity (DLT).

Determination of the safety, tolerability, and toxicity profile of administering TDO in metastatic or recurrent LMS patients, including assessment of dose-limiting toxicities (DLTs).

Clinical benefit rate (CBR), as defined by best response, (Complete Response (CR), Partial Response (PR) or Stable Disease (SD)) will be assessed using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1.

Janssen Scientific Affairs, LLC

University of Miami

Associate Professor

Skin and Connective Tissue Diseases

Liposarcoma

Histiocytoma, Malignant Fibrous

Chondrosarcoma

Sarcoma, Synovial

Liposarcoma, Myxoid

Histiocytoma

Neoplasms, Adipose Tissue

Neoplasms, Connective Tissue

Neoplasms, Fibrous Tissue

Undifferentiated Pleomorphic Sarcoma

Synovial Sarcoma

Myxoid Liposarcoma

Patients receive itacitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Itacitinib

Laboratory Biomarker Analysis

Lee Cranmer

This pilot phase I trial studies how well itacitinib works in treating patients with sarcomas that do not respond to treatment (refractory) and have spread to other parts of the body (advanced/metastatic). Itacitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

OUTLINE:

Patients receive itacitinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 7 and 30 days, every 12 weeks from baseline for up to 1 year, and then every 6 months thereafter.

Itacitinib in Treating Patients With Refractory Metastatic/Advanced Sarcomas

A Pilot Study Examining the Impact of the Jak1 Inhibitor Itacitinib on the Sarcoma Tumor Immune Microenvironment

Evaluation of the change in percentages of cells against the null hypothesis of no difference will be performed using a 1-sided t-test at the 0.05 level.

Will be graded according to Common Terminology Criteria for Adverse Events version 5.0. The frequency and severity of toxicities will be evaluated by proportions and associated 95% confidence intervals.

Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Distributions and percentages at landmark times for time to event outcomes will be estimated using the method of Kaplan-Meier. Confidence intervals about medians will be estimated using the method of Brookmeyer-Crowley. With 12 LMS patients, binary proportions can be estimated to within 29% with 95% confidence. With 8 (SS or MRCL) and PUS, respectively, binary proportions can be estimated to within 36% with 95% confidence.

Distributions and percentages at landmark times for time to event outcomes will be estimated using the method of Kaplan-Meier. Confidence intervals about medians will be estimated using the method of Brookmeyer-Crowley. With 12 LMS patients, binary proportions can be estimated to within 29% with 95% confidence. With 8 (SS or MRCL) and PUS, respectively, binary proportions can be estimated to within 36% with 95% confidence.

CR and PR will be defined as per RECIST 1.1 Distributions and percentages at landmark times for time to event outcomes will be estimated using the method of Kaplan-Meier. Confidence intervals about medians will be estimated using the method of Brookmeyer-Crowley. With 12 LMS patients, binary proportions can be estimated to within 29% with 95% confidence. With 8 (SS or MRCL) and PUS, respectively, binary proportions can be estimated to within 36% with 95% confidence.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Lurbinectedin + Doxorubicin In Leiomyosarcoma	NCT05099666	Advanced Soft-t... Metastatic Soft... Advanced Leiomy... Leiomyosarcoma ...	Lurbinectedin Doxorubicin	18 Years -	Massachusetts General Hospital
Trabectedin, Doxorubicin and Olaratumab in Patients With Metastatic or Recurrent Leiomyosarcoma	NCT03437070	Leiomyosarcoma	Trabectedin Doxorubicin Olaratumab	18 Years -	University of Miami
Itacitinib in Treating Patients With Refractory Metastatic/Advanced Sarcomas	NCT03670069	Metastatic Leio... Metastatic Syno... Metastatic Undi... Advanced Myxoid... Advanced Soft T... Metastatic Myxo... Metastatic Roun... Metastatic Soft... Refractory Leio... Refractory Myxo... Refractory Roun... Refractory Soft... Refractory Syno... Refractory Undi... Advanced Leiomy... Advanced Synovi... Advanced Undiff... Metastatic Chon...	Itacitinib Laboratory Biom...	18 Years -	Fred Hutchinson Cancer Center
Trabectedin, Doxorubicin and Olaratumab in Patients With Metastatic or Recurrent Leiomyosarcoma	NCT03437070	Leiomyosarcoma	Trabectedin Doxorubicin Olaratumab	18 Years -	University of Miami
Trabectedin, Doxorubicin and Olaratumab in Patients With Metastatic or Recurrent Leiomyosarcoma	NCT03437070	Leiomyosarcoma	Trabectedin Doxorubicin Olaratumab	18 Years -	University of Miami

Spots Global Cancer Trial Database for advanced leiomyosarcoma