L19TNF plus doxorubicin in patients with STS

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Philogen S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Oct 2017 → ongoing

Decision date (initial)

2024-05-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Philogen S.p.A.

External identifiers

EU CT number

2024-512789-32-00

EudraCT number

2016-003239-38

ClinicalTrials.gov

NCT04650984

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

The primary objective of the trial is to evaluate whether L19TNF in combination with doxorubicin given for advanced or metastatic soft tissue sarcoma prolongs progression free survival (PFS), as compared to doxorubicin alone.

Secondary objectives 1

1. To assess the efficacy, the following measurements will be considered: − Overall survival (OS) − Median Progression Free Survival (mPFS) − Median Overall Survival (mOS) − Overall Response Rate (ORR, consisting of CR and PR) and Best Overall Response Rate (BORR)

Conditions and MedDRA coding

Unresectable or metastatic soft tissue sarcoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Age 18 - 75 years.
2. 2. Patients must have histological evidence of advanced unresectable and/or metastatic high-grade soft tissue sarcoma (grade 2 – 3 according to the FNCLCC grading system) not amenable to curative treatment with surgery or radiotherapy and for which doxorubicin treatment is considered appropriate. Participants with Osteosarcoma, Chondrosarcoma, Ewing Sarcoma/ Primitive Neuroectodermal Tumor (PNET), Kaposi’s Sarcoma, Dermatofibrosarcoma protuberans, and Gastrointestinal Stromal Tumors (GIST) will be excluded
3. 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. 4. Life expectancy of at least 3 months.
5. 5. ECOG ≤ 2.
6. 6. Documented negative test for HIV-HBV-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. 7. Female patients: negative serum pregnancy test at screening for women of childbearing potential (WOCBP)*. WOCBP must agree to use, from the screening to six months following the last administration of L19TNF and/or Doxorubicin, 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 from the screening to four months following the last administration of L19TNF and/or Doxorubicin (e.g. condom with spermicidal gel). Double-barrier contraception is required.
8. 8. Informed consent signed and dated to participate in the study
9. 9. 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 27

1. 1. Prior therapy (except surgery and radiation) for unresectable or metastatic malignant soft tissue sarcoma.
2. 2. Previous treatment with anthracycline-containing chemotherapy.
3. 3. Radiotherapy within 4 weeks prior to therapy
4. 4. Known history of allergy to TNFα, anthracyclines or other intravenously administered human proteins/peptides/antibodies.
5. 5. Previous therapy with recombinant TNF.
6. 6. Absolute neutrophil count (ANC) < 1.5 x 109/L, platelets < 100 x 109/L and haemoglobin (Hb) < 9.0 g/dl.
7. 7. Chronically impaired renal function as expressed by creatinine ≥ 2.0 x ULN.
8. 8. Inadequate liver function (ALT, AST, ALP or total bilirubin ≥ 2.5 x ULN).
9. 9. Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol.
10. 10. History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
11. 11. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).
12. 12. Clinically significant cardiac arrhythmias or requiring permanent medication.
13. 13. Uncontrolled hypertension, despite optimal therapy.
14. 14. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine classification).
15. 15. Severe diabetic retinopathy such as severe non-proliferative retinopathy and proliferative retinopathy.
16. 16. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery) within 4 weeks of administration of study treatment.
17. 17. Pregnancy or breast-feeding.
18. 18. 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.
19. 19. 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.
20. 20. Known active or latent tuberculosis (TB).
21. 21. Concurrent malignancies other than Soft Tissue Sarcoma, unless the patient has been disease-free for at least 2 years.
22. 22. Growth factors or immunomodulatory agents within 7 days prior to the administration of study treatment.
23. 23. Serious, non-healing wound, ulcer or bone fracture.
24. 24. Allergy to study medication or excipients in study medication.
25. 25. Deep vein thrombosis, pulmonary embolism or other acute vascular events within 6 months.
26. 26. Anticoagulation therapy with P2Y12 antagonists (e.g., clopidogrel, ticagrelor) and vitamin K antagonists (e.g., phenprocoumon, warfarin)
27. 27. Concurrent use of other anti-cancer treatments or agents other than study medication.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The following efficacy endpoint will be considered: − Progression-free survival (PFS)

Secondary endpoints 1

1. To assess the safety profile of L19TNF combined with doxorubicin. The following safety endpoints will be considered: − Adverse Events (AEs) assessment based on CTCAE v.4.03. − Standard laboratory (haematology, biochemistry and urinalysis) parameters. − Physical examination findings including assessment of vital signs and physical measurements.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Philogen S.p.A.

Sponsor organisation

Philogen S.p.A.

Address

Piazza La Lizza 7

City

Siena

Postcode

53100

Country

Italy

Scientific contact point

Organisation

Philogen S.p.A.

Contact name

Teresa Hemmerle

Public contact point

Organisation

Philogen S.p.A.

Contact name

Teresa Hemmerle

Third parties 2

Locations

5 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 36 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications