| Eligibility |
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.
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