Dose Finding Study of L19TNF and Doxorubicin in Patients With STS

NCT04032964 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: PH-L19TNFDOX75-02/19
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The study is aimed at evaluating the safety of L19TNF in combination with the most appropriate dose of doxorubicin.

Conditions

Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (10)

• Number and type of Adverse events (AE)

  Adverse event (AE) for the assessment of safety (CTCAE v. 5.0)

  From week 1 to week 72

• Number and type of Serious Adverse events (SAE)

  Serious Adverse Events (SAE) for the assessment of safety (CTCAE v. 5.0)

  From week 1 to week 72

• Number and type of Drug induced liver injury (DILI)

  Drug induced liver injury (DILI) assessment based on CTCAE v.5.0

  From week 1 to week 72

• Electrocardiogram (ECG) findings

  Electrocardiogram (ECG) findings. In particular, data about QT/QTc intervals will be collected and analyzed for QT/QTc prolongation potentially caused by treatment.

  From week 1 to week 72

• Echocardiogram (ECHO) findings

  Echocardiogram (ECHO) findings. In particular, data about QT/QTc intervals will be collected and analyzed for QT/QTc prolongation potentially caused by treatment.

  From week 1 to week 72

• Calculation of the body surface area (BSA)

  BSA

  From week 1 to week 72

• Measurement of body weight

  Measurement of body weight

  From week 1 to week 72

• Heart rate

  Measurement of heart rate

  From week 1 to week 72

• Blood pressure

  Measurement of blood pressure

  From week 1 to week 72

• ECOG performance status

  From week 1 to week 72

Secondary Outcomes (6)

• Progression-free survival (PFS) rate

  3, 6, 9, 12 and 18 months

• Efficacy of L19TNF in combination with doxorubicin: Overall response rate

  3, 6, 9, 12 and 18 months

• Efficacy of L19TNF in combination with doxorubicin: Disease Control Rate

  3, 6, 9, 12 and 18 months

• HAFA measurement

  Treatment phase: at day 1 of cycle 1, at day 8 of week 1, at day 1 of cycle 2 and at day 1 of every cycle; at day 1 of every maintenance cycle (each cycle is 21 days)

• PK value of L19TNF

  Cycle 1 day 1, Cycle 1 day 2, cycle 1 day 3 and cycle 1 day 5 (each cycle is 21 days)

Study Arms (1)

Arm L19TNF + DOXO

EXPERIMENTAL

Patients will be treated with: * doxorubicin 75 mg/m2 i.v. on day 1 of each 21-day cycle; * L19TNF 13 µg/kg i.v. on day 1, 3 and 5 of each 21-day cycle

Drug: L19TNF; Drug: DOXORUBICIN

Interventions

L19TNF DRUG

L19TNF 13 µg/kg i.v. will be administered on day 1, 3 and 5 of each 21-day cycle

Arm L19TNF + DOXO

DOXORUBICIN DRUG

Doxorubicin 75 mg/m2 will be administered on day 1 of each 21-day cycle

Arm L19TNF + DOXO

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-85 years.
• Histologically confirmed diagnosis of advanced unresectable or metastatic soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy. Participants with Kaposi's sarcoma and gastrointestinal stromal tumors (GIST) will be excluded. Note: Evidence of disease progression is required for participants that are not newly diagnosed.
• Patients must have at least one unidimensionally measurable lesion by computed tomography as defined by RECIST criteria 1.1. If only one 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 ≤ 2.
• 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.
• 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:

• Diagnosis of GIST or Kaposi sarcoma.
• Prior therapy (except surgery and radiation) for this presentation of unresectable or metastatic malignant soft tissue sarcoma.
• Previous treatment with anthracycline- or anthracenedione-containing chemotherapy.
• Radiotherapy within 3 weeks (21 days) prior to therapy and previous radiation therapy to the mediastinal or pericardial area.
• Active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis). Participants with a history of a CNS metastasis previously treated with curative intent (for example, stereotactic radiation or surgery) that have not progressed on follow-up imaging, have been asymptomatic for at least 60 days and are not receiving systemic corticosteroids and or/anticonvulsants, are eligible. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before randomization to rule out brain metastasis.
• Known history of allergy to TNF, anthracyclines, or other intravenously administered human proteins/peptides/antibodies.
• Absolute neutrophil count (ANC) \< 1.5 x 109/L, platelets \< 100 x 109/L and hemoglobin (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, ALP or total bilirubin ≥ 2.5 x 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 (\> Grade II, New York Heart Association (NYHA) criteria).
• Clinically significant cardiac arrhythmias or requiring permanent medication.
• Abnormalities observed during baseline ECG and ECHO 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;

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (1)

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

Santa Monica, California, 90403, United States

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Doxorubicin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, phase 1 dose confirmation study in patients with advanced, unresectable and/or metastatic soft tissue sarcoma

Study Record Dates

• First Submitted: June 28, 2019
• First Posted: July 25, 2019
• Study Start: September 5, 2019
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: April 8, 2024

Record last verified: 2024-04

Locations

US (1)