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

NCT03420014 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: PH-L19TNFDOX2-02/17
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Leiomyosarcoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  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).

  From randomization up to week 72

Secondary Outcomes (19)

• Overall survival (OS)

  From week 1 up to week 72, every 6 weeks; from week 73 up to week 144, every 12 weeks;

• Overall response rate (ORR)

  1) From week 1 up to week 18, every 6 weeks; 2) from week 19 up to week 72, every 12 weeks (Maintenance); 3) EoT: at week 22/23 (only Induction) and at week 72 (Maintenance); 4) Follow-up: from week 22/23 (EoT) up to week 72, every 12 weeks.

• Duration of response (DOR)

  1) From week 1 up to week 18, every 6 weeks; 2) from week 19 up to week 72, every 12 weeks (Maintenance); 3) EoT: at week 22/23 (only Induction) and at week 72 (Maintenance); 4) Follow-up: from week 22/23 (EoT) up to week 72, every 12 weeks.

• Progression-free survival (PFS) rate

  1) From week 1 up to week 18, every 6 weeks; 2) from week 19 up to week 72, every 12 weeks (Maintenance); 3) EoT: at week 22/23 (only Induction) and at week 72 (Maintenance); 4) Follow-up: from week 22/23 (EoT) up to week 72, every 12 weeks.

• Overall survival (OS) rates

  From week 1 up to week 144.

Study Arms (2)

Arm 1: Doxorubicin

ACTIVE COMPARATOR

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

Drug: Doxorubicin

Arm 2: L19TNF plus doxorubicin

EXPERIMENTAL

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.

Combination Product: L19TNF plus doxorubicin

Interventions

Doxorubicin DRUG

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

Arm 1: Doxorubicin

L19TNF plus doxorubicin 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.

Arm 2: L19TNF plus doxorubicin

Eligibility Criteria

• Age: 16 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients may be included in the study if they meet all of the following criteria:
• Age ≥ 16 years. Patients under 18 years, should be fully grown (proof of fused growth plates).
• 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.
• 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.
• Life expectancy of at least 3 months in the judgment of the investigator.
• ECOG ≤ 1.
• 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.
• 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.
• 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.
• Informed consent signed and dated to participate in the study.
• 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).

You may not qualify if:

• Patients will be excluded from participating in this study if they meet one or more of the following criteria:
• Prior therapy (except surgery and radiation) for unresectable or metastatic malignant soft tissue sarcoma (STS).
• Patients with primary tumor localized to the extremities and a single resectable synchronous distant metastatic lesion.
• Patients eligible for neoadjuvant preoperative treatment.
• Previous treatment with anthracycline-containing chemotherapy.
• Radiotherapy within 4 weeks prior to start of therapy.
• Known history of allergy to TNFα, anthracyclines or other intravenously (IV) administered human proteins/peptides/antibodies.
• Absolute neutrophil count (ANC) \< 1.5 x 109/L, platelets \< 100 x 109/L and haemoglobin (Hb) \< 9.0 g/dl.
• Chronically impaired renal function as expressed by creatinine clearance \< 60 mL/min or serum creatinine \> 1.5 ULN.
• Inadequate liver function (ALT, AST, GGT, ALP or total bilirubin ≥ 1.5 x ULN) or total bilirubin ≥ 1.5 x ULN).
• International normalized ratio (INR) \> 1.5 ULN.
• Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol.
• History within the last year of cerebrovascular disease and/or acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
• Heart insufficiency (any grade, New York Heart Association (NYHA) criteria).
• Left Ventricular Ejection Fraction (LVEF) \< 50%.

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (8)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

RECRUITING

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

Santa Monica, California, 90403, United States

RECRUITING

Mayo Clinic Hospital

Jacksonville, Florida, 32224, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

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

New Brunswick, New Jersey, 08901, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43202, United States

RECRUITING

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

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Leiomyosarcoma

Interventions

Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Scott H. Okuno, M.D.

  Mayo Clinic, Rochester, MN

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Teresa Hemmerle, PhD

CONTACT

+39 057717816; regulatory@philogen.com

Serena Bettarini, Dr

CONTACT

+39 057717816; regulatory@philogen.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2018
• First Posted: February 5, 2018
• Study Start: December 27, 2018
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: October 10, 2023

Record last verified: 2023-10

Locations

US (8)