Cohort 1: Subjects with desmoid tumor Cohort 2: Subjects with desmoplastic small round cell tumor or Ewing sarcoma
Conditions
Interventions
Trade Name: Abraxane
Product Name: nab-paclitaxel
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: nab-Paclitaxel
CAS Number: 33069-62-4
Other descriptive name: P
Sponsors
Grupo Español de Investigación en Sarcomas (GEIS)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cohort 1: Desmoid tumor 1. Subjects must voluntarily sign the informed consent form before any study test is conducted that is not part of routine subject care. 2. Subjects with pathologic diagnosis of deep desmoid tumor of extremities, trunk wall or head and neck region. 3. Subjects must be symptomatic due to tumor desmoid mass. 4. Age: 18-80 years (both ages included). 5. Subjects could have received 1 previous chemotherapy line if the scheme was methrotrexate and vinca alkaloids. Importantly, if this is the case, it must be documented that symptoms have gotten worse or simptoms are stable in the context of disease progression (RECIST 1.1). 6. Availability of archive tumor block. 7. Measurable disease, according to RECIST 1.1 criteria. 8. Performance status =1 (ECOG). 9. Adequate respiratory functions: FEV1 > 1L. 10. Normal ECG values. 11. 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 = 10 times the ULN, total bilirubin = 1.25 times the ULN are acceptable. 12. 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. 13. HBV and HCV serologies must be performed prior to inclusion. If HbsAg is positive it is recommended to reject the existence of replicative phase (HbaAg+, DNA VHB+) remaining at investigators' discretion the preventive treatment with lamivudine. If a potential subject is positive for anti-HCV antibodies, presence of the virus should be ruled out with a qualitative PCR, or the subject should NOT be included in the study (if a qualitative PCR cannot be performed then subject will not be able to enter the study). Cohort 2: DSRCT and ES 1. Subjects (parent or tutor 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. 2. Subject diagnosed of relapsed/refractory desmoplastic small round cell tumor (DSRCT) or Ewing sarcoma. 3. DSRCT subjects must have received at least one previous poli-chemotherapy line. 4. Ewing sarcoma subjects must have received at least two standard chemotherapy lines. 5. Age = 6 months and = 40 years. 6. Availability of archive tumor blocks or slides (new biopsy recommended). 7. Measurable disease, according to RECIST 1.1 criteria. 8. Performance status =1 (ECOG). 9. Adequate respiratory functions: FEV1 > 1L. 10. Normal ECG values. 11. 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 = ULN, CPK = 2.5 times ULN, alkaline phosphatase = 2.5 times the ULN are acceptable. If alkaline phosphatase is > 2.5 times the ULN, then the alkaline phosphatase liver fraction and/or 5’ nucleotidase and/or GGT must be = ULN. 12. Men or women of child bearing potential should be using an effective method of contraception before entry into the study and throughout the same and for 6 months after ending the study. Women of childbearing potential must have a negative urine pregnancy test before study entry. 13. HBV and HCV serologies must be performed prior to inclusion. If HbsAg is posit
Exclusion criteria
Exclusion criteria: Cohort 1: Desmoid tumor 1. Less than 4 weeks elapsed since prior exposure to chemotherapy. 2. Subjects with desmoid tumor of abdominal cavity (abdominal wall is not an exclusion criteria) 3. Desmoid tumor with ill-defined margins. 4. Unavailability to undergo MRI. 5. Previously irradiated target lesion. 6. Pre-existing neuropathy greater than grade 1. 7. Other active invasive malignancy requiring ongoing therapy or expected to require systemic therapy within two years. However, localized squamous cell carcinoma of the skin, basal cell carcinoma of the skin, carcinoma in situ of the cervix or other malignancies requiring only locally ablative therapy, will not result in exclusion. 8. Concomitant anticancer therapy, immunotherapy or radiation therapy within prior 4 weeks. 9. 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 10. Hb < 9 g/dL. 11. Pregnant women are excluded due to the potential for teratogenic or abortifacient effects of nab paclitaxel because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued prior to participation of the mother on study. 12. Known hypersensitivity to protein bound paclitaxel 13. Any other concurrent condition that in the investigators opinion would jeopardize compliance with the protocol 14. Known positive test for infection by human immunodeficiency virus (HIV). 15. Subjects participating in another clinical trial or receiving any other investigational product. Cohort 2: DSRCT and ES 1. Less than 4 weeks elapsed since prior exposure to chemotherapy. 2. Pre-existing neuropathy greater than Grade 1. 3. Other active invasive malignancy requiring ongoing therapy or expected to require systemic therapy within two years. However, localized squamous cell carcinoma of the skin, basal cell carcinoma of the skin, carcinoma in situ of the cervix or other malignancies requiring only locally ablative therapy, will not result in exclusion. 4. Concomitant anticancer therapy, immunotherapy or radiation therapy within prior 4 weeks. 5. 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 6. Hb < 9 g/dL. 7. Pregnant women are excluded due to the potential for teratogenic or abortifacient effects of nab paclitaxel because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued prior to participation of the mother on study. 8. Known hypersensitivity to protein bound paclitaxel. 9. Any other concurrent condition that in the investigators opinion would jeopardize compliance with the protocol. 10. Known positive test for infection by human immunodeficiency virus (HIV). 11. Subjects participating in another clinical trial or receiving any other investigational product.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Cohort 1: Desmoid tumor: •To determine the objective response rate (ORR) in subjects with desmoid tumors, using RECIST 1.1 criteria. •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. Cohort 2: Desmoplastic small round cell tumor and Ewing sarcoma: •To determine the objective response rate (ORR) in subjects with desmoplastic small round cell tumor and Ewing sarcoma, using RECIST 1.1 criteria;Secondary Objective: Cohort 1: Desmoid tumor •To define the pattern of radiological response according to MRI parameters and to correlate it with CBR and Brief Pain Inventory (BPI) parameters. •To estimate the efficacy of nab-paclitaxel as measured by the progression-free survival (PFS) assessed by median time. •To analyze the variation of symptoms during the first year from trial enrollment in accordance with BPI and Analgesic Quantification Algorithm (AQA). •To evaluate the safety profile of nab-paclitaxel according to CTCAE 4.0. Cohort 2: Desmoplastic small round cell tumor and Ewing sarcoma: •To evaluate the safety profile of nab-paclitaxel according to CTCAE 4.0.;Primary end point(s): Cohort 1: Desmoid tumor •Objective response rate (ORR) (confirmed complete response [CR] and partial response [PR]), measured using RECIST 1.1 criteria. Response criteria will be based on the baseline identification of target lesions and radiological assessments every 3 months until tumor progression. •Clinical benefit rate (CBR), measured as CR+PR+SD for 3 months with improvement of pain with at least minimally important difference (MID) of 2. Cohorte 2: Desmoplastic small round cell tumor and Ewing sarcoma •Objective response rate (ORR) (confirmed complete response [CR] and partial response [PR]), measured using RECIST 1.1 criteria. Response criteria will be based on the baseline identification of target lesions and radiological assessments every 3 months unti | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Cohort 1: Desmoid tumor •Pattern of radiological response according to MRI parameters (decrease of contrast enhancement in T1-Gd wi, decrease of high signal in T2-wi; increase of low signal bands; increase of the ADC score of diffusion) correlated with CBR and BPI parameters. •Efficacy measured by the progression-free survival (PFS) rate assessed by median time. •Variation of symptoms during the first year from trial enrollment, measured with BPI and Analgesic Quantification Algorithm (AQA). •Safety profile of nab-paclitaxel, through assessment of adverse event type, incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests. Toxicity will be graded and tabulated by using NCI-CTCAE 4.0. Cohorte 2: Desmoplastic small round cell tumor and Ewing sarcoma •Safety profile of nab-paclitaxel, through assessment of adverse event type, incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests. Toxicity will be graded and tabulated by using NCI-CTCAE 4.0.;Timepoint(s) of evaluation of this end point: Cohort 1: Desmoid tumor •Pattern of radiological response according to MRI parameters: every 3 months •Efficacy measured by the progression-free survival (PFS) rate assessed by median time: every 3 months •Variation of symptoms during the first year from trial enrollment, measured with BPI and Analgesic Quantification Algorithm (AQA): during first year •Safety profile: at the end of the treatment Cohort 2: Desmoplastic small round cell tumor and Ewing sarcoma •Safety profile of nab-paclitaxel: at the end of the treatment | — |
Countries
Spain
Contacts
Public ContactClinical Trials
Sofpromed Investigación Clínica, SLU
Outcome results
None listed