First-in-man Clinical Trial of CEB-01 PLGA Membrane in Recurrent or Locally Advanced Retroperitoneal Soft Tissue Sarcoma

NCT04619056 | Completed Phase 1 DMC

• 2 other identifiers: CEB-01-RLS01-CT2018-001026-25
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 5

Brief Summary

This is an open label, first-in-man clinical trial to assess safety and tolerability of CEB-01 PLGA membrane in patients with recurrent or locally advanced retroperitoneal soft tissue sarcoma after surgery. The trial will be conducted in 3 dose-escalation cohorts (3 patients each, enrolling patients one by one, after 4 weeks of observation and agreement of Scientific Committee and DMC) and in an expansion cohort, using the highest safe and tolerable dose. The study will follow a 3+3 modified design; dose escalation will follow a modified Fibonacci method. CEB-01 carrying a SN-38 dose between 9 and 36 mg will be placed in the surgical bed at the time of tumor resection.

Conditions

Recurrent Soft Tissue Sarcoma; Locally Advanced Soft Tissue Sarcoma

Keywords

Soft tissue sarcoma; Retroperitoneal; Recurrent or locally advanced; CEB-01 PLGA membrane; SN-38; Local drug delivery system

Outcome Measures

Primary Outcomes (1)

• Recommended Doses for Phase II (Maximum tolerated dose)

  The number of patients experiencing dose limiting toxicities during the Dose Limiting Toxicities (DLT) observation period of 2 weeks.

  Through 2 weeks

Secondary Outcomes (6)

• Frequency of Adverse Events (AEs) (Safety)

  Through study completion, average 2 years

• Frequency of Treatment Related Adverse Events (TRAEs) (Toxicity)

  Through study completion, average 2 years

• Time to local relapse (TTLR)

  Through study completion, average 2 years

• Progression Free Survival (PFS)

  Through study completion, average 2 years

• Overall Survival (OS)(until 24 months of Follow Up (FU))

  Through study completion, average 2 years

Study Arms (3)

Cohort 1

EXPERIMENTAL

CEB-01 with total SN-38 dose: 9 mg

Drug: CEB-01 membrane loaded with SN-38

Cohort 2

EXPERIMENTAL

CEB-01 with total SN-38 dose: 18 mg

Drug: CEB-01 membrane loaded with SN-38

Cohort 3

EXPERIMENTAL

CEB-01 with total SN-38 dose: 36 mg

Drug: CEB-01 membrane loaded with SN-38

Interventions

CEB-01 membrane loaded with SN-38 DRUG

CEB-01 is a polymeric drug with a delivery system loaded with SN-38, and will be placed in the surgical bed at the time of tumor resection.

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years.
• Histologically confirmed diagnosis of locally advanced (T3 -T4, American Joint Committee on Cancer (AJCC)/primary tumor, regional lymph nodes, and distant metastases staging system (TMN) 8th Edition) and/or relapsed (any) retroperitoneal soft tissue sarcoma (liposarcoma, leiomyosarcoma, a solitary fibrous tumor (SFT), pleomorphic sarcoma, or a malignant nerve sheath tumor). Patients with local advanced (T3 -T4,AJCC/TMN 8th Edition) and/or relapse and metastatic disease who are candidates for local surgery without option of systemic treatment, are also eligible for the trial.
• Pathology specimens available for centralized review. Submission of formalin-fixed paraffin-embedded (FFPE) tumor tissue for central reviewing is required; if a FFPE block cannot be provided, then 10 unstained, positively-charged slides of 4-5 um thickness must be submitted.
• Size of tumor (visible or previously inadequately resected) \>5 cm at instrumental staging (CT, MRI).
• Normal liver, renal, hematological, and cardiac function as defined by biochemical and hematological parameters as follows: Hb \>11 g/dL, platelets \>100.000/mm3, White Blood Cells (WBC) \>3000/mm3, neutrophil count \>1500/mm3, albumin \>3.0 g/dl, Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) \<2.5 times the upper limit of normality (ULN), bilirubin \<2 times the ULN, creatinine \<1.5 mg/dl or creatinine clearance \> 60 ml/min.
• Eastern Cooperative Oncology Group (ECOG) Performance Status \<2.
• No concomitant radiotherapy or chemotherapy planned.
• Life expectancy greater than 6 months.
• Female subjects of childbearing potential must have a negative urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at time of screening.
• Men and women of childbearing potential must be willing to use adequate contraception throughout the study and for 3 months after surgery.
• Ability to understand and the willingness to sign a written informed consent document; subject has signed an Informed Consent Form (ICF) prior to any screening procedures and is able to comply with protocol requirements.

You may not qualify if:

• Pregnancy or lactation. Note: Pregnant women are excluded from this study; if the patient is a lactating mother, breastfeeding should be discontinued.
• Other malignancies within past 5 years, with the exception of carcinoma in situ of cervix and basocellular skin cancers treated with eradicating intent.
• Serious psychiatric disease that precludes informed consent or limits compliance
• Medical condition limiting survival to less than 6 months.
• Uncontrolled bacterial, viral or fungal infection.
• Active viral hepatitis or chronic liver disease.
• Impossibility of ensuring adequate follow-up.
• Contraindication to magnetic resonance imaging (MRI), including presence of a pacemaker or an aneurysm clip, severe claustrophobia, a known reaction to the gadolinium contrast dye, or body weight that could interfere with the feasibility of a MRI.
• Major surgery within 14 days prior to starting study drug or still in recovery after experiencing surgical complications; neither tumor biopsy nor central line insertion are considered a major surgery.
• Unable or unwilling to stop the use of herbal supplements; the use of nutritional supplements may be allowed after review by a study pharmacist to confirm no significant risk of interaction with eribulin or radiation.
• Other relevant concomitant illnesses.
• Patients previously treated with Irinotecan.

Sponsors & Collaborators

• CEBIOTEX: lead

Study Sites (5)

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, 08041, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Sarcoma; Recurrence

Interventions

Irinotecan

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Ana Sebio, M.D. Ph.D.

  Hospital Universitari de la Santa Creu i Sant Pau

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open label, first-in-human clinical trial that will be conducted in 3 dose-escalation cohorts (3-6 patients each) and in an expansion cohort, at the highest dose determined to be safe and tolerable. CEB-01 loaded with a SN-38 dose between 9 and 36 mg will be allocated to each patient.

Study Record Dates

• First Submitted: October 30, 2020
• First Posted: November 6, 2020
• Study Start: June 3, 2020
• Primary Completion: November 28, 2025
• Study Completion: November 28, 2025
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5)