Locally Advanced Soft Tissue SarcomaPhase 1/2NCT06217536
Neoadjuvant Lurbinectedin and Preoperative Radiation for Treating Soft Tissue Sarcomas
A Phase 1/2 study testing Lurbinectedin, Radiotherapy and Non-investigational surgery in people with Locally Advanced Soft Tissue Sarcoma, run by University of California, San Francisco.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Soft Tissue Sarcoma
- What is being tested?
- Lurbinectedin, Radiotherapy and Non-investigational surgery
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 31 Oct 2024to 31 Oct 2027
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have histologically or cytologically confirmed diagnosis of locally advanced soft tissue sarcoma of extremity, trunk or retroperitoneum that is resectable and for which preoperative radiotherapy is considered appropriate.
- Including metastatic (stage IV) disease for which radiotherapy and surgical resection of the primary tumor are indicated.
- Grade 1 myxoid liposarcoma can be included if preoperative radiotherapy is considered appropriate.
- For all other sarcomas, only grade 2 or 3 will be included.
- Those with locally recurrent sarcoma after surgery alone are eligible for enrollment if other inclusion criteria are met.
- Must have measurable disease defined as a tumor size at least >= 5 cm in the longest diameter as measured by Computerized tomography (CT) scan or Magnetic resonance imaging (MRI) for which radiation is feasible and indicated.
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- Age >=18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status <= 1 (Karnofsky ≥ 70%).
- Demonstrates adequate organ function within 21 days of Day 1 as defined below:
- Hemoglobin >= 9.0 g / dL.
- prothrombin time (PT) (or International Normalized Ratio (INR)) and partial thromboplastin time (PTT) (or activated partial thromboplastin time (aPTT)) <1.5 x upper limit of normal (ULN).
- Absolute neutrophil count >=1,500/microliter (mcL).
- Platelets >=100,000/mcL.
- Total bilirubin within normal institutional limits, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.
- Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT)<=3 X institutional upper limit of normal.
- Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) <=3 X institutional upper limit of normal.
- Alkaline phosphatase (ALP) < 2.5 × ULN.
- Creatinine <= 2 x within institutional upper limit of normal OR creatinine clearance Glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2, calculated using the Cockcroft-Gault equation, unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2.
- Ability to understand and the willingness to sign a written informed consent document.
- Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. For individuals with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- The effects of Lurbinectedin on the developing human fetus are unknown. For this reason and because Lurbinectedin used in this trial are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (2 methods of contraception including hormonal and barrier method of birth control) for the duration of study participation and for 6 months after last administration of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. A female is considered to be of childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) if she meets the following criteria:
- is postmenarchal,
- has not reached a postmenopausal state (>= 12 continuous months of amenorrhea with no identified cause other than menopause), and
- has not undergone surgical sterilization (removal of ovaries and/or uterus). - Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after last administration of study treatment.
Who cannot join
- Has the following histologic subtypes: gastrointestinal stromal tumor (GIST), desmoid, Ewing sarcoma, bone sarcomas, Kaposi sarcoma.
- Prior history of trabectedin or lurbinectedin treatment.
- Prior radiation therapy in excess of 20 Gray (Gy) conventionally fractionated radiotherapy (RT) to the site of the current diagnosis of sarcoma. No overlap with prior radiation fields in excess of 20 Gy is allowed.
- Currently receiving treatment in another invasive investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s).
- Known central nervous system (CNS) disease, except for treated brain metastasis: Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS); Gamma Knife, linear particle accelerator (LINAC), or equivalent) or a combination as deemed appropriate by the treating physician. Participants with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to lurbinectedin.
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- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Participants on strong or moderate cytochrome P450 (CYP)3A inducers or inhibitors and cannot be substituted for other drugs.
- Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this study.
- Has received systemic anti-cancer therapies within 3 weeks of first dose, radiation within 2 weeks, or antibody therapy within 4 weeks. Concomitant administration of Luteinizing hormone-releasing hormone (LHRH) analogues for prostate cancer and somatostatin analogues for neuroendocrine tumors are allowed as per standard of care.
- Has not recovered from adverse events due to prior anti-cancer therapy to <= grade 1 or baseline (other than alopecia).
- Is currently receiving any other investigational agents.
- Any concurrent illness in the opinion of the investigator would affect treatment compliance.
- Participants needing concurrent antiemetic aprepitant or any other Neurokinin 1 (NK1) antagonist or related Substance P-antagonists (except rolapitant).
- Pregnant participants are excluded from this study because lurbinectedin has the potential for teratogenic or abortifacient effects. Females of childbearing potential (definition as above) must undergo a urine pregnancy test per institutional guidelines within 7 days prior to Day 1 of study treatment. Participants with a positive urine pregnancy test are excluded.
- Breast-feeding participants are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lurbinectedin, breastfeeding should be discontinued if the mother is treated with lurbinectedin and for 2 weeks after the last dose.
- Participants of childbearing potential who are unwilling to use at least 2 highly effective methods of contraception during study treatment and for 90 days following the last dose of study treatment.
- Participants with a known history of collagen vascular disease on active therapy.
About this study
Official title: Phase 1b/2 Trial Using Neoadjuvant Lurbinectedin With Concurrent Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas of Extremity, Trunk, and Retroperitoneum
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.
Read the detailed description
PRIMARY OBJECTIVES:
Phase Ib:
- To determine the safety and tolerability of neoadjuvant lurbinectedin
- in combination with preoperative 2 weeks of hypofractionated radiation for extremity and trunk sarcoma, or
- with 6 weeks of conventionally fractionated radiation for retroperitoneal sarcoma II. To determine the maximum tolerated dose (MTD) for neoadjuvant lurbinectedin in combination with preoperative external beam radiation therapy (EBRT) in patients with sarcoma.
Phase II:
- To estimate the efficacy of neoadjuvant lurbinectedin in combination with preoperative EBRT (hypofractionated or conventionally fractionated), according to endpoint defined by sarcoma type and location:
- Cohort 1: extremity and trunk sarcoma (HFRT)
- Cohort 2: Extremity myxoid liposarcoma (HFRT)
- Cohort 3: Retroperitoneal sarcoma (CFRT course)
SECONDARY OBJECTIVES:
- Time to disease progression (local or distant recurrence).
II. Overall response rate (ORR) pre-operative as measured by RECIST 1.1 or a later tool for monitoring disease progression.
III. Overall survival.
IV. To grade radiation related skin toxicity overlying the tumor area.
- To determine long term major wound healing complications with the use of this combination in all cohorts.
EXPLORATORY OBJECTIVES:
- To evaluate changes in monocyte, macrophage, T cell, and RNA expression levels over time.
OUTLINE:
Participants will receive neoadjuvant lurbinectedin concurrent with radiation therapy. Non-investigational surgery will be performed 4-6 weeks from the end of radiation therapy. Participants with localized disease at the time of study enrollment will be on surveillance on-study for 2 years. Post-operatively participants will be followed every 12 +/- 4 weeks for approximately 2 years from the end of treatment. Participants with known metastatic disease will be followed until progression, toxicity and thereafter for 2 years.
- Conditions
- Locally Advanced Soft Tissue Sarcoma
- Being tested
- Lurbinectedin, Radiotherapy, Non-investigational surgery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LurbinectedinDrug
Also called Zepzelca
Given intravenously (IV)
RadiotherapyRadiation
Also called Radiation therapy
Conventionally fractionated radiotherapy or external beam radiation
Non-investigational surgeryProcedure or surgery
Non-investigational surgical procedure on tumor tissue
| Study group | Role | What they receive |
|---|---|---|
| Phase 1b, Cohort 1 (Extremity and Trunk Sarcoma) | Experimental | 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. Receives: Drug: Lurbinectedin; Radiation: Radiotherapy; Procedure: Non-investigational surgery |
| Phase 1b, Cohort 2 (Extremity Myxoid Liposarcoma) | Experimental | 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. Receives: Drug: Lurbinectedin; Radiation: Radiotherapy; Procedure: Non-investigational surgery |
| Phase 1b, Cohort 3: Retroperitoneal Sarcoma | Experimental | 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. Receives: Drug: Lurbinectedin; Radiation: Radiotherapy; Procedure: Non-investigational surgery |
| Phase 2, Cohort 1: Extremity and trunk sarcoma | Experimental | 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. Receives: Drug: Lurbinectedin; Radiation: Radiotherapy; Procedure: Non-investigational surgery |
| Phase 2, Cohort 2: Extremity myxoid liposarcoma | Experimental | 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. Receives: Drug: Lurbinectedin; Radiation: Radiotherapy; Procedure: Non-investigational surgery |
| Phase 2, Cohort 3: Retroperitoneal sarcoma | Experimental | 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. Receives: Drug: Lurbinectedin; Radiation: Radiotherapy; Procedure: Non-investigational surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants with dose-limiting toxicities (DLTs) (Phase 1b)
The proportion of participants with reported DLTs will be reported for
Measured: 4 weeks
Maximum Tolerated Dose (MTD) (Phase 1b)
MTD is defined as the highest dose at which no more than one instance of dose limiting toxicity (DLT) is observed among 1 of 6 participants treated.
Measured: Up to 6 months
Pathological necrosis rate (Phase 2, Cohort 1)
Pathological necrosis rate, defined as the proportion of participants with >=95% pathological necrosis.
Measured: Up to 12 weeks
Local control rate (Phase 2, Cohort 2)
Local control rate is defined as the proportion of participants with >=50% of the resected sample showing any histological treatment effect.
Measured: Up to 12 weeks
Overall response rate (Phase 2, Cohort 3)
Overall response rate is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: Up to 12 weeks
Secondary outcomes (5)
Median time to disease progression (TTP)
Time to progression is defined as the time from first day of study treatment to first documented occurrence of disease progression (including local and distant recurrences). Participants without progression will be censored at their last disease evaluation will be reported.
Measured: Up to 2 years
Overall Response Rate (ORR)
The proportion of pre-operative participants with a confirmed CR or PR as measured by RECIST 1.1 or a later tool for monitoring disease progression will be reported.
Measured: Up to 12 weeks
Median Overall Survival (OS)
The median overall survival time is defined as the time from first day of study treatment to death due to any cause will be reported. Participants who are still alive will be censored at their last date known to be alive.
Measured: Up to 2 years
Incidence of radiation related skin toxicity
Incidence of radiation related skin toxicity by grade as classified by the NCI CTCAE version 5.0 and additionally assessed by radiation oncologists will be reported.
Measured: Up to 6 months
Proportion of participants requiring wound care
The proportion of participants requiring secondary operation under general or regional anesthesia for wound repair, invasive procedure without general or regional anesthesia (mainly aspiration of seroma), readmission for wound care such as intravenous antibiotics, or persistent deep packing for 120 days (4 months) or longer will be reported.
Measured: Up to 4 months after non-investigational surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2024
- Study start31 Oct 2024 (estimated)
- Primary completion31 May 2026 (estimated)
- Study completion31 Oct 2027 (estimated)
Why it stopped: Business decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Soft Tissue SarcomaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Varun Monga, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06217536
- Sponsor's protocol ID
- 23872
- Other IDs
- NCI-2024-00107
- Status last verified
- Nov 2024
- First submitted
- 11 Jan 2024
- Last updated
- 18 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1b/2 Trial Using Neoadjuvant Lurbinectedin With Concurrent Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas of Extremity, Trunk, and Retroperitoneum
- ClinicalTrials.gov ID
- NCT06217536
- Acronym / sponsor ID
- 23872
- Conditions
- Locally Advanced Soft Tissue Sarcoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Business decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Study start
- 31 Oct 2024 (estimated)
- Primary completion
- 31 May 2026 (estimated)
- Study completion
- 31 Oct 2027 (estimated)
- First posted
- 22 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
Phase Ib:
- To determine the safety and tolerability of neoadjuvant lurbinectedin
- in combination with preoperative 2 weeks of hypofractionated radiation for extremity and trunk sarcoma, or
- with 6 weeks of conventionally fractionated radiation for retroperitoneal sarcoma II. To determine the maximum tolerated dose (MTD) for neoadjuvant lurbinectedin in combination with preoperative external beam radiation therapy (EBRT) in patients with sarcoma.
Phase II:
- To estimate the efficacy of neoadjuvant lurbinectedin in combination with preoperative EBRT (hypofractionated or conventionally fractionated), according to endpoint defined by sarcoma type and location:
- Cohort 1: extremity and trunk sarcoma (HFRT)
- Cohort 2: Extremity myxoid liposarcoma (HFRT)
- Cohort 3: Retroperitoneal sarcoma (CFRT course)
SECONDARY OBJECTIVES:
- Time to disease progression (local or distant recurrence).
II. Overall response rate (ORR) pre-operative as measured by RECIST 1.1 or a later tool for monitoring disease progression.
III. Overall survival.
IV. To grade radiation related skin toxicity overlying the tumor area.
- To determine long term major wound healing complications with the use of this combination in all cohorts.
EXPLORATORY OBJECTIVES:
- To evaluate changes in monocyte, macrophage, T cell, and RNA expression levels over time.
OUTLINE:
Participants will receive neoadjuvant lurbinectedin concurrent with radiation therapy. Non-investigational surgery will be performed 4-6 weeks from the end of radiation therapy. Participants with localized disease at the time of study enrollment will be on surveillance on-study for 2 years. Post-operatively participants will be followed every 12 +/- 4 weeks for approximately 2 years from the end of treatment. Participants with known metastatic disease will be followed until progression, toxicity and thereafter for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Phase 1b, Cohort 1 (Extremity and Trunk Sarcoma) | Experimental | Drug: Lurbinectedin, Radiation: Radiotherapy, Procedure: Non-investigational surgeryParticipants 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. |
| Phase 1b, Cohort 2 (Extremity Myxoid Liposarcoma) | Experimental | Drug: Lurbinectedin, Radiation: Radiotherapy, Procedure: Non-investigational surgeryParticipants 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. |
| Phase 1b, Cohort 3: Retroperitoneal Sarcoma | Experimental | Drug: Lurbinectedin, Radiation: Radiotherapy, Procedure: Non-investigational surgeryParticipants 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. |
| Phase 2, Cohort 1: Extremity and trunk sarcoma | Experimental | Drug: Lurbinectedin, Radiation: Radiotherapy, Procedure: Non-investigational surgeryParticipants 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. |
| Phase 2, Cohort 2: Extremity myxoid liposarcoma | Experimental | Drug: Lurbinectedin, Radiation: Radiotherapy, Procedure: Non-investigational surgeryParticipants 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. |
| Phase 2, Cohort 3: Retroperitoneal sarcoma | Experimental | Drug: Lurbinectedin, Radiation: Radiotherapy, Procedure: Non-investigational surgeryParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Must have histologically or cytologically confirmed diagnosis of locally advanced soft tissue sarcoma of extremity, trunk or retroperitoneum that is resectable and for which preoperative radiotherapy is considered appropriate.
- Those with locally recurrent sarcoma after surgery alone are eligible for enrollment if other inclusion criteria are met.
- Must have measurable disease defined as a tumor size at least >= 5 cm in the longest diameter as measured by Computerized tomography (CT) scan or Magnetic resonance imaging (MRI) for which radiation is feasible and indicated.
- Age >=18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status <= 1 (Karnofsky ≥ 70%).
Key exclusion criteria (18 listed)
- Has the following histologic subtypes: gastrointestinal stromal tumor (GIST), desmoid, Ewing sarcoma, bone sarcomas, Kaposi sarcoma.
- Prior history of trabectedin or lurbinectedin treatment.
- Prior radiation therapy in excess of 20 Gray (Gy) conventionally fractionated radiotherapy (RT) to the site of the current diagnosis of sarcoma. No overlap with prior radiation fields in excess of 20 Gy is allowed.
- Currently receiving treatment in another invasive investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s).
- Known central nervous system (CNS) disease, except for treated brain metastasis: Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS); Gamma Knife, linear particle accelerator (LINAC), or equivalent) or a combination as deemed appropriate by the treating physician. Participants with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LurbinectedinAlso: ZepzelcaGiven intravenously (IV) | Drug | Phase 1b, Cohort 1 (Extremity and Trunk Sarcoma), Phase 1b, Cohort 2 (Extremity Myxoid Liposarcoma), Phase 1b, Cohort 3: Retroperitoneal Sarcoma, Phase 2, Cohort 1: Extremity and trunk sarcoma, Phase 2, Cohort 2: Extremity myxoid liposarcoma, Phase 2, Cohort 3: Retroperitoneal sarcoma |
| RadiotherapyAlso: Radiation therapyConventionally fractionated radiotherapy or external beam radiation | Radiation | Phase 1b, Cohort 1 (Extremity and Trunk Sarcoma), Phase 1b, Cohort 2 (Extremity Myxoid Liposarcoma), Phase 1b, Cohort 3: Retroperitoneal Sarcoma, Phase 2, Cohort 1: Extremity and trunk sarcoma, Phase 2, Cohort 2: Extremity myxoid liposarcoma, Phase 2, Cohort 3: Retroperitoneal sarcoma |
| Non-investigational surgeryNon-investigational surgical procedure on tumor tissue | Procedure or surgery | Phase 1b, Cohort 1 (Extremity and Trunk Sarcoma), Phase 1b, Cohort 2 (Extremity Myxoid Liposarcoma), Phase 1b, Cohort 3: Retroperitoneal Sarcoma, Phase 2, Cohort 1: Extremity and trunk sarcoma, Phase 2, Cohort 2: Extremity myxoid liposarcoma, Phase 2, Cohort 3: Retroperitoneal sarcoma |
Primary outcome
Proportion of participants with dose-limiting toxicities (DLTs) (Phase 1b)
Time frame: 4 weeks
The proportion of participants with reported DLTs will be reported for
Maximum Tolerated Dose (MTD) (Phase 1b)
Time frame: Up to 6 months
MTD is defined as the highest dose at which no more than one instance of dose limiting toxicity (DLT) is observed among 1 of 6 participants treated.
Pathological necrosis rate (Phase 2, Cohort 1)
Time frame: Up to 12 weeks
Pathological necrosis rate, defined as the proportion of participants with >=95% pathological necrosis.
Local control rate (Phase 2, Cohort 2)
Time frame: Up to 12 weeks
Local control rate is defined as the proportion of participants with >=50% of the resected sample showing any histological treatment effect.
Overall response rate (Phase 2, Cohort 3)
Time frame: Up to 12 weeks
Overall response rate is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
5 secondary outcomes
Median time to disease progression (TTP)
Time frame: Up to 2 years
Overall Response Rate (ORR)
Time frame: Up to 12 weeks
Median Overall Survival (OS)
Time frame: Up to 2 years
Incidence of radiation related skin toxicity
Time frame: Up to 6 months
Proportion of participants requiring wound care
Time frame: Up to 4 months after non-investigational surgery
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Varun Monga, MD principal investigator
University of California, San Francisco
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lurbinectedin, Radiotherapy and Non-investigational surgery in people with Locally Advanced Soft Tissue Sarcoma, run by University of California, San Francisco.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with dose-limiting toxicities (DLTs) (Phase 1b) (time frame: 4 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2024.