A phase 2 trial on propranolol in combination with pembrolizumab in advanced Angiosarcoma and Undifferentiated Pleomorphic Sarcoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Hovedstaden

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 Dec 2022 → ongoing

Decision date (initial)

2024-05-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Nordic Cancer Union

External identifiers

EU CT number

2024-513727-16-00

EudraCT number

2021-003788-82

ClinicalTrials.gov

NCT05961761

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Therapy, Efficacy, Safety

Determine the progression-free survival rate (PFSR) at 3 months by Response Evaluation Criteria in Solid Tumors (RECIST v1.1)

Secondary objectives 5

1. Determine the objective response rate (ORR) and duration of Response (DOR) using RECIST v 1.1.
2. Determine Progression Free Survival (PFS) and Overall Survival (OS).
3. Safety and tolerability of the combination of pembrolizumab and propranolol.
4. Determine Quality of Life (QoL)
5. Exploratory: To explore the association between anti-tumor activity and specific biomarker measures in the tumor tissue and in peripheral blood

Conditions and MedDRA coding

Advanced Angiosarcoma and Undifferentiated Pleomorphic Sarcoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care
2. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
3. Histologically confirmed diagnosis of unresectable locally advanced or metastatic Angiosarcoma or Undifferentiated Pleomorphic Sarcoma, who has progressed/failed to provide clinical benefit on first line standard chemotherapy.
4. Age ≥18 years
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of ≤2 at the time of enrollment.
6. Evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).
7. Available material from archived formalin-fixed paraffin-embedded tumor tissue obtained within 3 months of study enrollment for biomarkerrelated studies. If not sufficient or available, a newly obtained core or excisional biopsy of a tumor lesion may be performed.
8. Absolute neutrophil count (ANC) ≥ 1 x 10⁹/L
9. Platelet count ≥ 75 x 10⁹/L
10. Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin ≤ 50 mmol/L)
11. Aspartate transaminase (AST)/Alanine transaminase (ALT) ≤ 5 x ULN
12. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (using the Cockcroft-Gault formula)
13. Women of childbearing potential (WOCBP): Agreement to use contraceptive methods with a failure rate of < 1 % per year during the treatment period and for at least 120 days after the treatment. Safe contraceptive methods for women are birth control pills, intrauterine device, contraceptive injection, contraceptive implant,contraceptive patch or contraceptive vaginal ring.
14. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year during the treatment period and for at least 120 days after the treatment.
15. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception

Exclusion criteria 16

1. Have an anticipated life expectancy of <3 months.
2. Moderate to severe degree of bronchial asthma or chronic obstructive pulmonary disease.
3. Acute or non-stable congestive heart failure
4. Any other condition listed as contraindication for treatment with propranolol according to SPC
5. Have received any previous systemic therapy targeting the PD-1/PDL-1 signaling pathway or other immune checkpoint inhibitors.
6. Have received propranolol within 4 weeks prior to treatment
7. Prior to study day one received radiation therapy, chemotherapy or targeted small molecule therapy within 2 weeks and/or monoclonal antibody treatment within 4 weeks
8. Not recovered from the effects of previously administered agents
9. Clinically active or unstable CNS metastases as assessed by the treating physician
10. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results
11. Participants with active, known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
12. Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
13. Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
14. History of allergy to study drug components
15. History of severe hypersensitivity reaction to any monoclonal antibody
16. WOCBP who are pregnant or breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of patients alive with CR, PR and SD according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) at 3 months

Secondary endpoints 4

1. Percentage of patients with CR and PR, including duration hereof using RECIST v 1.1
2. Median PFS and OS
3. Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE) v5.0
4. The 30 item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ C30) questionnaire

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Hovedstaden

Sponsor organisation

Region Hovedstaden

Address

Borgmester Ib Juuls Vej 1

City

Herlev

Postcode

2730

Country

Denmark

Scientific contact point

Organisation

Region Hovedstaden

Contact name

Coordinating Investigator Niels Junker

Public contact point

Organisation

Region Hovedstaden

Contact name

Coordinating Investigator Niels Junker

Third parties 2

Locations

3 EU/EEA countries · 4 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 10 files

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

Application history

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