Neoadjuvant Lurbinectedin and Preoperative Radiation for Treating Soft Tissue Sarcomas

Conditions

• Locally Advanced Soft Tissue Sarcoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Lurbinectedin — DRUG
  Given intravenously (IV)
• Radiotherapy — RADIATION
  Conventionally fractionated radiotherapy or external beam radiation
• Non-investigational surgery — PROCEDURE
  Non-investigational surgical procedure on tumor tissue

Study Details

This is a multi-center, multi-arm open-label phase Ib/II clinical study assessing the efficacy of concurrent lurbinectedin in combination with radiotherapy in patients with locally advanced, resectable, high-grade sarcomas.

Key Dates

Start date

Oct 31, 2024

Status verified

Nov 2024

Primary completion

May 31, 2026

Completion

Oct 31, 2027

Study Design

Enrollment

0 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Phase 1b, Cohort 1 (Extremity and Trunk Sarcoma)
  Participants will receive up to 3.2 mg/m\^2 of neoadjuvant lurbinectedin IV once every cycle (a cycle is 21 days) in combination with 2 weeks of pre-operative radiation given as 35 Gy in 5 fractions (gross tumor volume (GTV)) with fractions administered at least every other day starting on cycle 2 for participants with extremity and trunk sarcoma. Non-investigational surgery will take place 4-6 weeks after completion of radiation therapy. Participants with metastatic disease at the time of study enrollment may be able to continue study treatment for 2 years from the time of initiating treatment. Participants with localized disease at the time of study enrollment may continue study treatment for approximately 3 months AND then be followed on-study surveillance.
• Experimental: Phase 1b, Cohort 2 (Extremity Myxoid Liposarcoma)
  Participants will receive up to 3.2 mg/m\^2 of neoadjuvant lurbinectedin IV once every cycle (a cycle is 21 days) in combination with 2 weeks of pre-operative radiation given as 35 Gy in 5 fractions (gross tumor volume (GTV)) with fractions administered at least every other day starting on cycle 2 for participants with extremity myxoid Liposarcoma. Non-investigational surgery will take place 4-6 weeks after completion of radiation therapy. Participants with metastatic disease at the time of study enrollment may be able to continue study treatment for 2 years from the time of initiating treatment. Participants with localized disease at the time of study enrollment may continue study treatment for approximately 3 months AND then be followed on-study surveillance.
• Experimental: Phase 1b, Cohort 3: Retroperitoneal Sarcoma
  Participants will receive up to 3.2 mg/m\^2 of neoadjuvant lurbinectedin IV once every cycle (a cycle is 21 days) in combination with 6 weeks of pre-operative conventional external beam radiation therapy given as 45-50.4 Gy delivered over 25-28 fractions starting on cycle 1 for participants with retroperitoneal sarcoma. Non-investigational surgery will take place 4-6 weeks after completion of radiation therapy. Participants with metastatic disease at the time of study enrollment may be able to continue study treatment for 2 years from the time of initiating treatment. Participants with localized disease at the time of study enrollment may continue study treatment for approximately 3 months AND then be followed on-study surveillance.
• Experimental: Phase 2, Cohort 1: Extremity and trunk sarcoma
  Participants will receive the maximum tolerated dose of neoadjuvant lurbinectedin IV once every cycle (a cycle is 21 days) in combination with 2 weeks of pre-operative radiation given as 35 Gy in 5 fractions (gross tumor volume (GTV)) with fractions administered at least every other day starting on cycle 2 for participants with extremity and trunk sarcoma. Non-investigational surgery will take place 4-6 weeks after completion of radiation therapy. Participants with metastatic disease at the time of study enrollment may be able to continue study treatment for 2 years from the time of initiating treatment. Participants with localized disease at the time of study enrollment may continue study treatment for approximately 3 months AND then be followed on-study surveillance.
• Experimental: Phase 2, Cohort 2: Extremity myxoid liposarcoma
  Participants will receive the maximum tolerated dose of neoadjuvant lurbinectedin IV once every cycle (a cycle is 21 days) in combination with 2 weeks of pre-operative radiation given as 35 Gy in 5 fractions (gross tumor volume (GTV)) with fractions administered at least every other day starting on cycle 2 for participants with extremity myxoid Liposarcoma. Non-investigational surgery will take place 4-6 weeks after completion of radiation therapy. Participants with metastatic disease at the time of study enrollment may be able to continue study treatment for 2 years from the time of initiating treatment. Participants with localized disease at the time of study enrollment may continue study treatment for approximately 3 months AND then be followed on-study surveillance.
• Experimental: Phase 2, Cohort 3: Retroperitoneal sarcoma
  Participants will receive the maximum tolerated dose of neoadjuvant lurbinectedin IV once every cycle (a cycle is 21 days) in combination with 6 weeks of pre-operative conventional external beam radiation therapy given as 45-50.4 Gy delivered over 25-28 fractions starting on cycle 1 for participants with retroperitoneal sarcoma. Non-investigational surgery will take place 4-6 weeks after completion of radiation therapy. Participants with metastatic disease at the time of study enrollment may be able to continue study treatment for 2 years from the time of initiating treatment. Participants with localized disease at the time of study enrollment may continue study treatment for approximately 3 months AND then be followed on-study surveillance.

Primary Outcome Measure

Proportion of participants with dose-limiting toxicities (DLTs) (Phase 1b) [ Time Frame: 4 weeks ]