Propranolol and Pembrolizumab in Advanced Soft Tissue Sarcoma Patients

NCT05961761 | Recruiting Phase 2

• 1 other identifier: SA2115
• Study Type: interventional
• Target: 80
• Locations: 3 countries
• Sites: 4

Brief Summary

The goal of this phase 2 clinical trial is to test efficacy and tolerability of combining propranolol and pembrolizumab in patients with advanced angiosarcoma or undifferentiated pleomorphic sarcoma. The main questions aims to answer:

• Primary: determine the progression-free survival rate (PFSR) at 3 months Secondary: determine the objective response rate (ORR), duration of Response (DOR), Progression Free Survival (PFS), Overall Survival (OS). Ensure the safety and tolerability, Determine Quality of Life (QoL)
• Exploratory: Characterize the TME Participants will be asked to ensure
• Baseline biopsy and further optional biopsies
• Treatment propranolol 40 mg BID and pembrolizumab 2 mg/kg Q3 weeks
• Evaluation, blood counts, QoL and blood samples for biomarkers according to schedule

Conditions

Soft Tissue Sarcoma Adult; Angiosarcoma; Undifferentiated Pleomorphic Sarcoma

Keywords

Immunotherapy; Propranolol; Pembrolizumab; PD-1 inhibitor; Sarcoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival rate

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

  3 months

Secondary Outcomes (6)

• Objective response rate

  Approximately 6 months

• Duration of Response

  Up to 2 years

• Progression Free Survival

  Up to 2 years

• Overall Survival

  Up to 2 years

• Safety of the treatment

  Up to 2 years

Study Arms (1)

Propranolol + pembrolizumab

EXPERIMENTAL

pembrolizumab 2 mg/kg every 3 weeks and propranolol 40 mg x2 daily until progression, unacceptable toxicity or patient withdrawal for a maximum of two years.

Drug: Propranolol; Drug: Pembrolizumab

Interventions

Propranolol DRUG

propranolol 40 mg x2 daily

Also known as: Betablocker

Propranolol + pembrolizumab

Pembrolizumab DRUG

pembrolizumab 2 mg/kg every 3 weeks

Also known as: anti PD-1

Propranolol + pembrolizumab

Eligibility Criteria

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

You may qualify if:

• 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
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
• 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.
• Age ≥18 years
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of ≤2 at the time of enrollment.
• Evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).
• Available material from archived formalin-fixed paraffin-embedded tumor tissue obtained within 3 months of study enrollment for biomarker related studies. If not sufficient or available, a newly obtained core or excisional biopsy of a tumor lesion may be performed.
• Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1 x 10⁹/L
• Platelet count ≥ 75 x 10⁹/L
• Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin ≤ 50 mmol/L)
• Aspartate transaminase (AST)/Alanine transaminase (ALT) ≤ 5 x ULN
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (using the Cockcroft-Gault formula)
• 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.
• 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.

You may not qualify if:

• Have an anticipated life expectancy of \<3 months.
• Moderate to severe degree of bronchial asthma or chronic obstructive pulmonary disease.
• Acute or non-stable congestive heart failure
• Any other condition listed as contraindication for treatment with propranolol according to SPC
• Have received any previous systemic therapy targeting the PD-1/PDL-1 signaling pathway or other immune checkpoint inhibitors.
• Have received propranolol within 4 weeks prior to treatment.
• 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.
• Not recovered from the effects of previously administered agents
• Clinically active or unstable CNS metastases as assessed by the treating physician
• 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
• 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
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
• 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.
• Age ≥18 years
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of ≤2 at the time of enrollment.

Sponsors & Collaborators

• Niels Junker: lead
• Aarhus University Hospital: collaborator
• Oslo University Hospital: collaborator
• Karolinska University Hospital: collaborator

Study Sites (4)

Aarhus University Hospital

Aarhus, 8200, Denmark

NOT YET RECRUITING

Herlev Gentofte Hospital

Herlev, 2730, Denmark

RECRUITING

Oslo University Hospital

Oslo, Norway

RECRUITING

Karolinska University Hospital

Stockholm, Sweden

NOT YET RECRUITING

MeSH Terms

Conditions

Hemangiosarcoma; Histiocytoma, Malignant Fibrous; Sarcoma

Interventions

Propranolol; pembrolizumab; spartalizumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Histiocytoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Niels Junker, MD, PhD

  Herlev and Gentofte Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Niels Junker, MD, PhD

CONTACT

+4538682973; Niels.Junker@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Consultant, MD, PhD, Principal Investigator

Model Details: A Simon´s optimum two-stage design

Study Record Dates

• First Submitted: June 13, 2023
• First Posted: July 27, 2023
• Study Start: August 17, 2021
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 27, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); DK (2); NO (1)