Treatment of Metastatic Soft Tissue Sarcoma (STS) Patients (FIBROSARC USA)

NCT ID: NCT03420014

Last Updated: 2023-10-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

114 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-27

Study Completion Date

2025-12-31

Brief Summary

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The present study is an open-label, randomized, controlled, two-arm multi-center study of the efficacy of L19TNF treatment in combination with doxorubicin versus doxorubicin alone in metastatic leiomyosarcoma patients.

Detailed Description

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In the study, 122 patients will be randomized in a 1:1 ratio to receive doxorubicin treatment (Arm 1) or L19TNF treatment in combination with doxorubicin (Arm 2).

The primary objective of the trial is to evaluate if L19TNF in combination with doxorubicin (Arm 2) given for metastatic leiomyosarcoma improves efficacy measured as progression free survival, as compared to doxorubicin alone (Arm 1).

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

Conditions

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Leiomyosarcoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1: Doxorubicin

Patients will receive a fixed dose doxorubicin, administered as a 15 ± 5 minutes i.v. infusion.

Group Type ACTIVE_COMPARATOR

Doxorubicin

Intervention Type DRUG

75 mg/m2 doxorubicin will be administered once every 3 weeks (Day 1 of every 21-days cycle).

Arm 2: L19TNF plus doxorubicin

Patients will receive a fixed dose of L19TNF in combination with a fixed dose doxorubicin.

Doxorubicin will be administered as a 15 ± 5 minutes i.v. infusion on day 1 of each 21-day cycle followed by at least 30 minutes pause before starting infusion of L19TNF.

Group Type EXPERIMENTAL

L19TNF plus doxorubicin

Intervention Type COMBINATION_PRODUCT

13 μg/kg L19TNF will be administered on day 1, 3 and 5 of every 21-days cycle in combination with 60 mg/m2 doxorubicin on day 1 of every 21-days cycle.

Interventions

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Doxorubicin

75 mg/m2 doxorubicin will be administered once every 3 weeks (Day 1 of every 21-days cycle).

Intervention Type DRUG

L19TNF plus doxorubicin

13 μg/kg L19TNF will be administered on day 1, 3 and 5 of every 21-days cycle in combination with 60 mg/m2 doxorubicin on day 1 of every 21-days cycle.

Intervention Type COMBINATION_PRODUCT

Eligibility Criteria

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Inclusion Criteria

Patients may be included in the study if they meet all of the following criteria:

1. Age ≥ 16 years. Patients under 18 years, should be fully grown (proof of fused growth plates).
2. Patients with histological evidence of stage IV metastatic high-grade leiomyosarcoma (grade 2 - 3 according to the Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system) not amenable to curative treatment with surgery or radiotherapy.
3. Patients must have at least one unidimensionally measurable lesion by computed tomography as defined by Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1. If only 1 lesion is present at screening this lesion should not have been irradiated during previous treatments.
4. Life expectancy of at least 3 months in the judgment of the investigator.
5. ECOG ≤ 1.
6. Documented negative test for HIV, HBV and HCV. For HBV serology, the determination of HBsAg and anti-HBcAg-Ab is required. In patients with serology documenting previous exposure to HBV, 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. Female patients: negative serum pregnancy test for women of childbearing potential (WOCBP)\* within 14 days of starting treatment. WOCBP must agree to use, from the screening to six months following the last study drug administration, highly effective contraception methods, as defined by the "Recommendations for contraception and pregnancy testing in clinical trials" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group (www.hma.eu/ctfg.html) and which include, for instance, progesterone-only or combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion, vasectomized partner or sexual abstinence.
8. Male patients: Male subjects able to father children must agree to use two acceptable methods of contraception throughout the study (e.g., condom with spermicidal gel). Double-barrier contraception is required.
9. Informed consent signed and dated to participate in the study.
10. Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

* Women of childbearing potential are defined as females who have experienced menarche, are not postmenopausal (12 months with no menses without an alternative medical cause) and are not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy).

Exclusion Criteria

Patients will be excluded from participating in this study if they meet one or more of the following criteria:

1. Prior therapy (except surgery and radiation) for unresectable or metastatic malignant soft tissue sarcoma (STS).
2. Patients with primary tumor localized to the extremities and a single resectable synchronous distant metastatic lesion.
3. Patients eligible for neoadjuvant preoperative treatment.
4. Previous treatment with anthracycline-containing chemotherapy.
5. Radiotherapy within 4 weeks prior to start of therapy.
6. Known history of allergy to TNFα, anthracyclines or other intravenously (IV) administered human proteins/peptides/antibodies.
7. Absolute neutrophil count (ANC) \< 1.5 x 109/L, platelets \< 100 x 109/L and haemoglobin (Hb) \< 9.0 g/dl.
8. Chronically impaired renal function as expressed by creatinine clearance \< 60 mL/min or serum creatinine \> 1.5 ULN.
9. Inadequate liver function (ALT, AST, GGT, ALP or total bilirubin ≥ 1.5 x ULN) or total bilirubin ≥ 1.5 x ULN).
10. International normalized ratio (INR) \> 1.5 ULN.
11. Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol.
12. History within the last year of cerebrovascular disease and/or acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
13. Heart insufficiency (any grade, New York Heart Association (NYHA) criteria).
14. Left Ventricular Ejection Fraction (LVEF) \< 50%.
15. Clinically significant cardiac arrhythmias or requiring permanent medication.
16. Abnormalities observed during baseline ECG and Echocardiogram investigations that are considered as clinically significant by the investigator. Subjects with current, or a history of QT/QTc prolongation would be excluded. In particular:

* patients with a marked prolongation of QT/QTc interval (e.g., repeated demonstration of QTc \>480 milliseconds using Fredricia's QT correction formula) are excluded;
* patients with a history of risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of prolonged QT syndrome) are excluded;
* patients who require the use of concomitant medications that prolong the QT/QTc interval are excluded.
17. Uncontrolled hypertension, despite optimal therapy.
18. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine classification).
19. Severe diabetic retinopathy such as severe non-proliferative retinopathy and proliferative retinopathy.
20. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery) within 4 weeks of administration of study treatment.
21. Pregnancy or breast-feeding.
22. 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.
23. 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.
24. Known active or latent tuberculosis (TB).
25. Concurrent malignancies other than soft tissue sarcoma (STS), unless the patient has been disease-free for at least 2 years.
26. Growth factors or immunomodulatory agents within 7 days prior to the administration of study treatment.
27. Serious, non-healing wound, ulcer or bone fracture.
28. Allergy to study medication or excipients in study medication.
29. Concurrent therapy with anticoagulants.
30. Concurrent use of other anti-cancer treatments or agents other than study medication.
31. Any recent live vaccination within 4 weeks prior to treatment or plan to receive vaccination during the study.
Minimum Eligible Age

16 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Philogen S.p.A.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Scott H. Okuno, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic, Rochester, MN

Locations

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Mayo Clinic Hospital

Phoenix, Arizona, United States

Site Status RECRUITING

Sarcoma Oncology Research Center (SORC) Cancer Center of Southern California

Santa Monica, California, United States

Site Status RECRUITING

Mayo Clinic Hospital

Jacksonville, Florida, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

Washington University

St Louis, Missouri, United States

Site Status RECRUITING

Rutgers Cancer Institute of New Jersey 195 Little Albany Street New Brunswick, NJ 08901 Room 2031

New Brunswick, New Jersey, United States

Site Status RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status RECRUITING

Seattle Cancer Care Alliance 825 Eastlake Ave. E. Seattle, WA 98109 Mail Stop CE2-128

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Teresa Hemmerle, PhD

Role: CONTACT

+39 057717816

Serena Bettarini, Dr

Role: CONTACT

+39 057717816

Facility Contacts

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Mahesh Seetharam, MD

Role: primary

Sant P Chawla, MD

Role: primary

Steven Attia, MD

Role: primary

904-953-7292

Scott Okuno, MD

Role: primary

Mia Weiss, MD

Role: primary

Sarah Weiss, MD

Role: primary

David A Liebner, MD

Role: primary

Lee Cranmer, MD

Role: primary

Other Identifiers

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PH-L19TNFDOX2-02/17

Identifier Type: -

Identifier Source: org_study_id

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