Luspatercept in Metastatic AGCT of the Ovary

February 8, 2024 updated by: University Health Network, Toronto

Luspatercept in Metastatic Adult Granulosa Cell Tumor (AGCT) of the Ovary

This is a single participant study of luspatercept for the treatment of a patient with dult granulosa cell tumor (AGCT) of the ovary.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This patient has AGCT driven by a somatic oncogenic FOXL2 mutation identified through a molecular profiling study. One of the ways in which this mutation drives tumorigenesis is via increased activity of SMAD3, which results in decreased expression of follistatin and allows increased signalling of activin, a TGFB ligand that activates the TGFB pathway. Anti-TGFB approaches have shown promise in preclinical studies of AGCTs and several early phase trials are investigating different levels of TGFB pathway inhibition1.

As an activin receptor ligand trap, luspatercept has been shown to reduce SMAD2/3 signaling and improve anemia in disorders characterized by ineffective erythropoiesis, such as B-thalassemia and myelodysplastic syndromes (MDSs). This study aims to determine if we can apply this rationale to a patient with recurrent AGCT with oncogenic FOXL2 mutation known to drive TGFB/SMAD pathway overactivity.

Luspatercept has not been investigated in AGCT and therefore the efficacy of this specific agent as a cancer therapeutic is not yet known. Other TFGB ligand-trapping agents are in development and early phase clinical trials. One such example is AVID200, a TGFB ligand trap and selective inhibitor of TGFB1 and advanced solid tumors. There were 19 patients included in a phase I study of AVID200 monotherapy in patients with advanced solid tumors. A best response of stable disease for over 12 weeks seen in two patients (adenoid cystic carcinoma and breast carcinoma). The maximum tolerated dose was not reached; no Grade 3 adverse events were seen and only three adverse events were reported overall including diarrhea and lipase elevation.

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • N/A

Exclusion Criteria:

  • N/A

This patient's case was recently discussed in the hospital expert molecular tumor board rounds consisting of representatives from specialist genomic profiling and gynecologic medical oncology departments. The discussion surrounded the best next therapeutic option in this rare cancer subtype without clear standard of care guidelines. The recommendation from this discussion was to investigate targets of the TGFβ pathway, such as luspatercept. Therefore, specific eligibility criteria aside from individual patient's medical history is not applicable.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Luspatercept in metastatic AGCT of the ovary
Luspatercept, 1.0 mg/kg, subcutaneously, every three weeks
Drug: Luspatercept
Erythroid Maturation Agent
Other Names:
  • Reblozyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response
Time Frame: From baseline CT until disease progression or until the investigator deems that it is in the patient's best interest to stop study treatment, whichever came first, assessed up to 3 months.
By computed tomography (CT) scans
From baseline CT until disease progression or until the investigator deems that it is in the patient's best interest to stop study treatment, whichever came first, assessed up to 3 months.
Eastern Cooperative Oncology Group (ECOG) score
Time Frame: From baseline ECOG until disease progression or until the investigator deems that it is in the patient's best interest to stop study treatment, whichever came first, assessed up to 3 months.

0. Fully active, able to carry on all pre-disease performance without restriction

  1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
  2. Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
  3. Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
  4. Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
  5. Death
From baseline ECOG until disease progression or until the investigator deems that it is in the patient's best interest to stop study treatment, whichever came first, assessed up to 3 months.
Circulating tumor DNA (ctDNA) levels
Time Frame: From baseline ctDNA until disease progression or until the investigator deems that it is in the patient's best interest to stop study treatment whichever came first, assessed up to 3 months..
Observe change between baseline ctDNA until disease progression
From baseline ctDNA until disease progression or until the investigator deems that it is in the patient's best interest to stop study treatment whichever came first, assessed up to 3 months..

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: Amit Oza, M.D., Princess Margaret Cancer Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 30, 2022

Primary Completion (Actual)

August 22, 2022

Study Completion (Actual)

August 29, 2022

Study Registration Dates

First Submitted

May 26, 2022

First Submitted That Met QC Criteria

February 8, 2024

First Posted (Actual)

February 12, 2024

Study Record Updates

Last Update Posted (Actual)

February 12, 2024

Last Update Submitted That Met QC Criteria

February 8, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OZUHN-015
  • 22-5326 (Other Identifier: University Health Network)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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