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JOURNAL ONKOLOGIE – STUDIE

FIBROSARC A Study Comparing the Efficacy of L19TNF+Doxorubicin vs Doxorubicin Alone as First-line Therapy in Patients With Advanced or Metastatic Soft Tissue Sarcoma

Rekrutierend

NCT-Nummer:
NCT04650984

Studienbeginn:
November 2017

Letztes Update:
03.12.2020

Wirkstoff:
Onfekafusp alfa, Doxorubicin

Indikation (Clinical Trials):
Sarcoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Philogen S.p.A.

Collaborator:
-

Kontakt

Studienlocations (2 von 2)

Studien-Informationen

Detailed Description:

Phase III, open label, randomized, controlled study in subjects with advanced or metastatic

soft tissue sarcoma. In the study, 102 patients will be enrolled and parallel assigned in a

1:1 fashion to one of two different arms, as follows:

- ARM 1: Patients will receive 75 mg/m2 doxorubicin once every 3 weeks (reference

treatment).

- ARM 2: Patients will receive 13 µg/kg L19TNF on days 1, 3 and 5 every 3 weeks in

combination with 60 mg/m2 doxorubicin (once every 3 weeks).

Anti-cancer activity will be assessed every 6 weeks during therapy and every 12 weeks

thereafter. Median PFS, PFS rates at 3, 6, 9, 12 and 18 months, mOS, OS rate at 12 and 18

months and ORR will be calculated.

Safety assessment will be performed on an ongoing basis during study participation, including

standard laboratory assessments. The incidence of AEs will be summarized by severity in all

patients with at least one study drug intake.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Patients aged 18-75 years.

2. Patients must have histological evidence of advanced unresectable and/or metastatic

high-grade soft tissue sarcoma (grade 2 - 3 according to the FNLCC grading system) not

amenable to curative treatment with surgery or radiotherapy. The following tumor types

are included:

- Malignant fibrous histiocytoma

- Myxoid and round cell liposarcoma, pleomorphic liposarcoma or dedifferentiated

- Liposarcoma

- Pleomorphic rhabdomyosarcoma

- Myxofibrosarcoma intermediate and high-grade

- Fibrosarcoma

- Leiomyosarcoma

- Angiosarcoma

- Alveolar rhabdomyosarcoma

- Unclassified sarcoma NOS

The following tumor types will not be included:

- GIST

- Mixed mesodermal tumor

- Chondrosarcoma

- Synovial sarcoma

- Malignant peripheral nerve sheath tumor

- Epithelioid sarcoma

- Embryonal rhabdomyosarcoma

- Malignant mesothelioma

- Neuroblastoma

- Osteosarcoma

- Ewing's sarcoma / primitive neuroectodermal tumor

- Desmoplastic small round cell tumor

- Alveolar soft part sarcoma

3. Patients must have at least one unidimensionally measurable lesion by computed

tomography as defined by RECIST criteria 1.1. This lesion should not have been

irradiated during previous treatments.

4. Life expectancy of at least 3 months.

5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

6. Documented negative test for HIV-HBV-HCV. For HBV serology: the determination of

HBsAg, anti-HBsAg-Ab and anti-HBCAg-Ab is required. In patients with serology

documenting previous exposure to HBV (i.e., anti-HBs Ab with no history of vaccination

and/or anti-HBc Ab), negative serum HBV-DNA is required. For HCV: HCV-RNA or HCV

antibody test. Subjects with a positive test for HCV antibody but no detection of

HCV-RNA indicating no current infection are eligible.

7. Negative serum pregnancy test for females of childbearing potential* within 14 days of

starting treatment.

8. Informed consent signed and dated to participate in the study.

9. Willingness and ability to comply with the scheduled visits, treatment plan,

laboratory tests and other study procedures.

Exclusion Criteria:

1. Prior therapy (except surgery and radiation) for unresectable or metastatic malignant

soft tissue sarcoma.

2. Previous treatment with anthracycline-containing chemotherapy.

3. Radiotherapy within 4 weeks prior to therapy.

4. Known history of allergy to TNFα, anthracyclines or other intravenously administered

human proteins/peptides/antibodies.

5. Absolute neutrophil count (ANC) < 1.5 x 109/L, platelets < 100 x 109/L and haemoglobin

(Hb) < 9.0 g/dl.

6. Chronically impaired renal function or creatinine ≥ 2.0 x ULN.

7. Inadequate liver function (ALT, AST, ALP or total bilirubin ≥ 2.5 x ULN.

8. Any severe concomitant condition which makes it undesirable for the patient to

participate in the study or which could jeopardize compliance with the protocol.

9. History within the last year of acute or subacute coronary syndromes including

myocardial infarction, unstable or severe stable angina pectoris.

10. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).

11. Clinically significant cardiac arrhythmias or requiring permanent medication.

12. Uncontrolled hypertension, despite optimal therapy.

13. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine

classification).

14. Severe diabetic retinopathy such as severe non-proliferative retinopathy and

proliferative retinopathy.

15. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery)

within 4 weeks of administration of study treatment.

16. Pregnancy or breast-feeding.

17. Requirement of chronic administration of corticosteroids or other immunosuppressant

drugs. Limited use of corticosteroids to treat or prevent acute hypersensitivity

reactions is not considered an exclusion criterion.

18. Presence of active and uncontrolled infections or other severe concurrent disease,

which, in the opinion of the investigator, would place the patient at undue risk or

interfere with the study.

19. Known active or latent tuberculosis (TB).

20. Concurrent malignancies other than Soft Tissue Sarcoma, unless the patient has been

disease-free for at least 2 years.

21. Growth factors or immunomodulatory agents within 7 days prior to the administration of

study treatment.

22. Serious, non-healing wound, ulcer or bone fracture.

23. Allergy to study medication or excipients in study medication.

24. Concurrent therapy with anticoagulants.

25. Concurrent use of other anti-cancer treatments or agents other than study medication.

Studien-Rationale

Primary outcome:

1. Median Progression free survival (mPFS) (Time Frame - From randomization up to week 72):
Progression-free survival PFS in a time-to-event analysis in the L19TNF plus Doxorubicin control group (Arm 2) versus the Doxorubicin alone treatment group (Arm 1).



Secondary outcome:

1. PFS rate (Time Frame - At 3, 6, 9, 12, 18 months after randomization):
Progression Free Survival

2. Overall Response Rate (ORR) (Time Frame - At 3, 6, 9, 12, 18 months after randomization):
Rate of Complete Response and Partial Response of L19TNF plus Doxorubicin treatment group (Arm 2) versus Doxorubicin alone (Arm 1).

3. Overall survival (OS) (Time Frame - At 12 months and 18 months after randomization):
OS in the L19TNF plus Doxorubicin treatment group (Arm 2) versus Doxorubicin alone (Arm 1)

4. Median Overall survival (mOS) (Time Frame - At 12 months and 18 months after randomization):
mOS in the L19TNF plus Doxorubicin treatment group (Arm 2) versus Doxorubicin alone (Arm 1).

5. Adverse Events (Time Frame - From week 1 up to week 72):
Number of patients with adverse events (AEs) assessed on CTCAE v.4.03

6. HAFA assessment (Time Frame - At day 1 of week 1 and week 2; at day 1 from week 4 up to week 18, every 3 weeks; at week 22-23 (EoT); at week 23-24 (first follow-up visit)):
Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19TNF (Arm 2).

Studien-Arme

  • Active Comparator: Arm 1
    Patients will receive 75 mg/m2 doxorubicin once every 3 weeks (reference treatment).
  • Experimental: Arm 2
    Patients will receive 13 µg/kg L19TNF on days 1, 3 and 5 every 3 weeks in combination with 60 mg/m2 doxorubicin (once every 3 weeks).

Geprüfte Regime

  • Onfekafusp alfa (L19TNF):
    Patients will receive a fixed dose of L19TNF in combination with a fixed dose of doxorubicin.
  • Doxorubicin:
    Patients will receive a fixed dose doxorubicin, administered as a 15 ± 5 minutes i.v. infusion.

Quelle: ClinicalTrials.gov


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