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)

TD Cohort

Inclusion Criteria:

1. 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.
2. 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.
3. 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.
4. Age: ≥ 6 months.
5. 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.
6. Availability of archive tumor block.
7. Measurable disease, according to RECIST 1.1 criteria.
8. Performance status ≤1 (ECOG).
9. Normal ECG values.
10. 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.
11. 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.
12. 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).

Exclusion Criteria:

1. Prior taxane therapy for any indication.
2. Less than 4 weeks elapsed since prior exposure to chemotherapy.
3. More than one previous chemotherapy line.
4. Subjects with desmoid tumor of abdominal cavity (abdominal wall is not an exclusion criterion)
5. Desmoid tumor with ill-defined margins.
6. Unavailability to undergo MRI.
7. Previously irradiated target lesion (if radiation dose exceeded 50 Gy).
8. Pre-existing neuropathy greater than grade 1.
9. 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.
10. Concomitant anticancer therapy, immunotherapy or radiation therapy within prior 4 weeks.
11. 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
12. Hb < 9 g/dL.
13. Women who are pregnant or breast-feeding.
14. Known hypersensitivity to protein bound paclitaxel
15. Any other concurrent condition that in the investigators opinion would jeopardize compliance with the protocol
16. Known positive test for infection by human immunodeficiency virus (HIV).
17. Subjects participating in another clinical trial or receiving any other investigational product.

DSRCT and ES Cohort

Inclusion Criteria:

1. Subjects or legal guardian 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´s sarcoma.
3. DSRCT subjects must have received at least one previous poli-chemotherapy line.
4. Ewing´s sarcoma subjects must have received at least two standard chemotherapy lines.
5. Age ≥ 6 months
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 ≥ 1.25 times 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 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).
14. Prior taxane therapy for any indication is accepted.
15. > Grade 3 (intense and diffuse) expression of SPARC by immunohistochemistry.

Exclusion criteria:

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. Women who are pregnant or breast-feeding.
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.