Luspatercept in Metastatic AGCT of the Ovary

NCT ID: NCT06254781

Last Updated: 2024-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-30
• Study Completion Date: 2022-08-29

Brief Summary

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

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.

Conditions

Adult Granulosa Cell Tumor of the Ovary

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Luspatercept in metastatic AGCT of the ovary

Luspatercept, 1.0 mg/kg, subcutaneously, every three weeks

Group Type: EXPERIMENTAL

Luspatercept

Intervention Type: DRUG

Erythroid Maturation Agent

Interventions

Luspatercept

Erythroid Maturation Agent

Intervention Type: DRUG

Other Intervention Names

Reblozyl

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amit Oza, M.D.

Role: PRINCIPAL_INVESTIGATOR

Princess Margaret Cancer Centre

Locations

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

22-5326

Identifier Type: OTHER

Identifier Source: secondary_id

OZUHN-015

Identifier Type: -

Identifier Source: org_study_id