Trial of Nab-paclitaxel in Patients With Desmoid Tumors and Multiply Relapsed/Refractory Desmoplastic Small Round Cell Tumors and Ewing Sarcoma

NCT03275818 | Completed Phase 2

• 2 other identifiers: GEIS-392016-002464-14
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 7

Brief Summary

A two-cohort, fase II, open-label, non-randomized, multicenter clinical trial. 14 sites in Spain. Cohort 1: Subjects with desmoid tumor (DT) Cohort 2: Subjects with desmoplastic small round cell tumor or Ewing sarcoma (DSRCT and ES) Nab-paclitaxel (ABRAXANE) will be administered as follows: Age ≥ 21 and ≤ 80 years: 125 mg/m2 days 1, 8 and 15 in cycles of 28 days Age ≥ 6 months and ≤ 20 years: 240 mg/m2 days 1, 8 and 15 in cycles of 28 days Subjects in the DT cohort will receive a maximum of three cycles. Subjects in the DSRCT and ES cohort will receive unlimited cycles until disease progression, the subject begins a new anticancer treatment, withdrawal of parent/guardian/subject consent/assent, parent/guardian/subject refusal, physician decision, toxicity that cannot be managed by dose delay or dose reduction alone or the study ends for any reason. The main goal is to determine the objective response rate (ORR), using RECIST 1.1 criteria and to determine the clinical benefit rate (CBR), defined as CR+PR+SD for 3 months with improvement of pain with at least minimally important difference (MID) of 2 in subjects with desmoid tumors (DT cohort) and to determine the objective response rate (ORR) in subjects with desmoplastic small round cell tumor and Ewing sarcoma, using RECIST 1.1 criteria (DSRCT and ES cohort)

Conditions

Tumor, Desmoplastic Small Round Cell, Adult; Tumor, Desmoplastic Small Round Cell, Childhood; Sarcoma, Ewing; Sarcoma; Desmoid

Keywords

sarcoma; Desmoid tumor; Desmoplastic small round cell tumor; Ewing sarcoma; relapsed; refractory

Outcome Measures

Primary Outcomes (2)

• Overall response rate (ORR) - cohort 1

  TD cohort: Overall response rate (ORR) according to RECIST 1.1 and/or clinical benefit rate (CBR) at 3 months with pain improvement of at least 2 points in the Brief Pain Inventory - Short Form (BPI-SF)

  3 months

• Objective response rate (ORR) - cohort 2

  DSRCT and SE cohort: To determine the objective response rate (ORR) in subjects with desmoplastic small round cell tumor and Ewing's sarcoma, using RECIST 1.1 criteria

  2 months

Secondary Outcomes (6)

• Pattern of radiological response - cohort 1

  3 months

• Progression-free survival - cohort 1

  3 months

• Variation of symptoms - cohort 1

  during first year

• Variation of physical function - cohort 1

  during first year

• Safety profile of nab-paclitaxel - cohort 1

  up to 12 months

Study Arms (1)

nab-paclitaxel

EXPERIMENTAL

nab-paclitaxel (ABRAXANE) will be administered as follows: * Age ≥ 21: 125 mg/m2 days 1, 8 and 15 in cycles of 28 days * Age ≥ 6 months and ≤ 20 years: 240 mg/m2 (for patients weighing \> 10 kg) and 11.5 mg/kg (for patients weighing ≤ 10 kg) on days 1, 8 and 15 in cycles of 28 days

Drug: nab paclitaxel

Interventions

nab paclitaxel DRUG

Subjects in the DT cohort will receive a maximum of three cycles. Subjects in the DSRCT and ES cohort will receive unlimited cycles until disease progression, the subject begins a new anticancer treatment, withdrawal of parent/guardian/subject consent/assent, parent/guardian/subject refusal, physician decision, toxicity that cannot be managed by dose delay or dose reduction alone or the study ends for any reason

Also known as: Abraxane

nab-paclitaxel

Eligibility Criteria

• Age: 6 Months - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects (parent or legal guardian if subject under 18 years) must voluntarily sign the informed consent form before any study test is conducted that is not part of routine subject care.
• Subjects with pathologic diagnosis of deep desmoid tumor of extremities, trunk wall or head and neck region.Intra-abdominal desmoid tumor cases could be enrolled if harboring betacatenin mutation.
• Subjects must be symptomatic (pain) due to tumor desmoid mass or lack physical function due to desmoid tumor mass, or in RECIST progression in the last 6 months.
• Age: ≥ 6 months.
• Subjects could have received one previous chemotherapy line if the scheme was methotrexate plus vinca alkaloids. Patients who received prostaglandin inhibitors or hormone therapy are also eligible.
• Availability of archive tumor block.
• Measurable disease, according to RECIST 1.1 criteria.
• Performance status ≤1 (ECOG).
• Normal ECG values.
• Adequate bone marrow function (hemoglobin ≥ 9 g/dL, leukocytes ≥ 3.000/mm3, neutrophils ≥ 1.500/mm3, platelets ≥ 100.000/mm3). Subjects with plasma creatinine ≤ 1.6 mg/dl, transaminases ≤ 2.5 times the ULN, total bilirubin ≤ 1.25 times the ULN are acceptable.
• Men or women of childbearing potential must use an effective method of contraception before entry into the study and throughout the same and for 6 months after ending the study treatment. Women of childbearing potential must have a negative urine or serum pregnancy test before study entry.

You may not qualify if:

• Prior taxane therapy for any indication.
• Less than 4 weeks elapsed since prior exposure to chemotherapy.
• More than one previous chemotherapy line.
• Desmoid tumor with ill-defined margins.
• Unavailability to undergo MRI.
• Previously irradiated target lesion (if radiation dose exceeded 50 Gy).
• Pre-existing neuropathy greater than grade 1.
• Concomitant anticancer therapy, immunotherapy or radiation therapy within prior 4 weeks.
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring IV antibiotic, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness or social situations that would limit compliance with study requirements
• Hb \< 9 g/dL.
• Women who are pregnant or breast-feeding.
• Known hypersensitivity to protein bound paclitaxel
• Any other concurrent condition that in the investigators opinion would jeopardize compliance with the protocol
• Known positive test for infection by human immunodeficiency virus (HIV).
• Subjects participating in another clinical trial or receiving any other investigational product.

Sponsors & Collaborators

• Grupo Espanol de Investigacion en Sarcomas: lead

Study Sites (7)

H. de la Santa Creu i Sant Pau

Barcelona, Spain

Location

H. Sant Joan de Déu

Barcelona, Spain

Location

H.U. 12 de Octubre

Madrid, Spain

Location

H.U.Niño Jesús

Madrid, Spain

Location

H.U. Virgen del Rocío

Seville, 41013, Spain

Location

H.U i Politècnic La Fe

Valencia, Spain

Location

H.U. Miguel Servet

Zaragoza, Spain

Location

MeSH Terms

Conditions

Neoplasms; Sarcoma, Ewing; Sarcoma; Desmoid Tumors; Desmoplastic Small Round Cell Tumor; Recurrence

Interventions

Taxes; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Javier Martin Broto, MD

  Hospitales Universitarios Virgen del Rocío

  STUDY DIRECTOR

• Jaume Mora, MD

  Hospital Sant Joan de Deu

  STUDY DIRECTOR

• Javier Martínez Trufero, MD

  Hospital Miguel Servet

  PRINCIPAL INVESTIGATOR

• Francisco Bautista, MD

  Hospital Universitario Niño Jesús

  PRINCIPAL INVESTIGATOR

• Antonio López Pousa, MD

  Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

  PRINCIPAL INVESTIGATOR

• Roberto Díaz, MD

  Hospital Universitario La Fe

  PRINCIPAL INVESTIGATOR

• José Antonio López-Martín, MD

  Hospital Universitario 12 de Octubre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2017
• First Posted: September 8, 2017
• Study Start: May 9, 2017
• Primary Completion: September 30, 2021
• Study Completion: September 30, 2021
• Last Updated: June 7, 2022

Record last verified: 2022-04

Locations

ES (7)