Secondary AngiosarcomaPhase 2NCT04873375
Cemiplimab for Secondary Angiosarcomas
A Phase 2 study testing Cemiplimab in people with Secondary Angiosarcoma and Locally Advanced Sarcoma, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Secondary angiosarcomas are aggressive mesenchymal tumors with a poor prognosis and limited therapeutic options. Recent studies conducted in patients with cutaneous squamous-cell carcinoma provide evidence that cemiplimab has the potential to be an effective treatment also for patients with secondary angiosarcomas. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Secondary Angiosarcoma, Locally Advanced Sarcoma, Metastasis
- What is being tested?
- Cemiplimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Jan 2022to 18 Oct 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patient aged ≥ 18 years.
- Signed written informed consent.
- Histologically confirmed diagnosis of progressive unresectable locally advanced or metastatic secondary angiosarcoma.
- Patients in the first line of systemic treatment unfit for chemotherapy and patients in advanced lines of systemic treatment.
- Measurable disease per RECIST 1.1 or per physical examination / daylight photography (WHO Offset Publication No. 48) as determined by the investigator.
- Tumour tissue material available (archival or recent tumour biopsy).
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- WHO ECOG 0-2.
- Hepatic function:
- Total bilirubin ≤ 1.5 x ULN (if liver metastases: ≤ 3 x ULN).
- Transaminases ≤ 3 x ULN (if liver metastases: ≤ 5 x ULN).
- Patients with Gilbert's Disease and total bilirubin up to 3x ULN may be eligible after communication with and approval from the medical monitor
- Alkaline phosphatase ≤ 2.5 x ULN (if liver OR bone metastases ≤5 x ULN).
- Renal function: serum creatinine ≤ 2 x ULN or estimated CrCl > 30 mL/min.
- Creatine phosphokinase (CPK) (also known as CK [creatine kinase]) elevation ≤ grade 2
- Bone marrow function:
- Hemoglobulin ≥ 9.0 g/dL.
- ANC ≥ 1.5 x 109/L.
- Platelet count ≥ 75 x 109/L.
- Expected life expectancy of at least 3 months as judged by the investigator.
Who cannot join
- Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs. The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 Diabetes mellitus, residual hypothyroidism that required only hormone therapy, or psoriasis that does not require systematic treatment.
- Prior treatment with immune checkpoint inhibitors.
- Continuous immunosuppressive corticosteroid treatment (doses > 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab. Note: patients who require a brief course of steroids (e.g. as prophylaxis for imaging studies) are not excluded.
- Active uncontrolled infection requiring therapy, including infection with HIV, active infection with HBV or HCV.
- History of pneumonitis within the last 5 years.
- Untreated brain metastasis(es) that may be considered active.
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- Note in clarification: Patients with previously treated brain metastases may participate provided that the lesion(s) is (are) stable (without evidence of progression for at least 6 weeks on imaging obtained in the screening period), and there is no evidence of new or enlarging brain metastases, and the patients do not require any immunosuppressive doses of systemic corticosteroids for management of brain metastasis(es) within 28 days of the first dose of cemiplimab.
- Patients with allergy or hypersensitivity to cemiplimab or to any of the excipients must be excluded. Specifically, because of the presence of trace components in cemiplimab, patients with allergy or hypersensitivity to doxycycline or tetracycline are excluded.
- History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments
- Patients with a history of solid organ transplant (patients with prior corneal transplants may be allowed to enroll after discussion with and approval from the medical monitor).
- Any anticancer treatment other than radiation therapy (chemotherapy, targeted systemic therapy, imiquimod, photodynamic therapy), investigational or standard of care, within 30 days of the initial administration of cemiplimab or planned to occur during the study period
- Receipt of live vaccines (including attenuated) within 30 days of first study treatment
- Prior use of PI3K-D inhibitors
- Women of childbearing potential (WOCBP)*, or sexually active men, who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment prior to the start of the first treatment, during the study, and for at least 6 months after the last dose.
- Breastfeeding
- Positive serum pregnancy test (a false positive pregnancy test, if demonstrated by serial measurements and negative ultrasound, will not be exclusionary, upon communication with and approval from the medical monitor)
- Any other condition that might interfere with experimental treatment and the study procedures as judged by the investigator.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Cemiplimab Treatment in Patients with Locally Advanced and Metastatic Secondary Angiosarcomas
Secondary angiosarcomas are aggressive mesenchymal tumors with a poor prognosis and limited therapeutic options. Recent studies conducted in patients with cutaneous squamous-cell carcinoma provide evidence that cemiplimab has the potential to be an effective treatment also for patients with secondary angiosarcomas.
The purpose of this study is to evaluate the overall response rate after 24 weeks of cemiplimab treatment in patients with locally advanced or metastatic secondary angiosarcomas.
The investigators hypothesis is that cemiplimab could be an effective treatment for patients diagnosed with locally advanced and metastatic secondary angiosarcomas.
Read the detailed description
Study design: A prospective, interventional, non-randomized, multicenter, phase II clinical trial.
Hypothesis:
Cemiplimab is registered for the use in patients with cutaneous squamous-cell carcinoma. In these patient groups cemiplimab showed impressive results. There are numerous similarities between cutaneous squamous-cell carcinoma and secondary angiosarcomas. Based on these similarities, including a complex genetic background, PD-L1 expression and MYC expression, the investigators hypothesize that cemiplimab might be an effective treatment for locally advanced and metastatic secondary angiosarcomas.
Primary Objective:
To evaluate the overall response rate (ORR) after 24 weeks of cemiplimab in secondary angiosarcomas, according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 or daylight photography as per WHO Offset Publication No. 48.
Secondary Objectives:
Secondary objectives include the establishment of the best ORR, median time to response, duration of response and progression free survival. The secondary objectives also comprise safety and toxicity quantification and to investigate the relation between response to cemiplimab and various tumor characteristics.
Study Population:
Patients eligible for inclusion are at least 18 years of age, with adequate organ function, who have a histologically confirmed diagnosis of progressive unresectable locally advanced or metastatic secondary angiosarcoma. Patients eligible are patients in the first line of treatment if they are unfit for chemotherapy and patients in advanced lines of systemic treatment. Major exclusion criteria include significant ongoing autoimmune disease that requires immunosuppressive treatment, prior treatment with immune checkpoint inhibitors, active uncontrolled infections or recent pneumonitis. All patients will provide Informed Consent prior to inclusion in the study and during the course of the trial, al relevant data will be stored in electronic Case Report Forms (eCRF).
Treatment Schedule:
After study inclusion, patients will be treated with Cemiplimab 350mg intravenously every three weeks. Patients will receive treatment until disease progression or discontinuation due to unacceptable toxic effects, withdrawal of consent or other reasons. The maximum treatment period will be two years, as is standard of care for patients treated with immunotherapy.
- Conditions
- Secondary Angiosarcoma, Locally Advanced Sarcoma, Metastasis
- Being tested
- Cemiplimab
- Keywords
- Secondary Angiosarcoma, Cemiplimab, immunotherapy, Angiosarcoma, Sarcoma
- Medical subject headings
- Neoplasm Metastasis, Hemangiosarcoma, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CemiplimabDrug
Also called LIBTAYO
After inclusion patients will be treated with Cemiplimab 350mg intravenously every three weeks
| Study group | Role | What they receive |
|---|---|---|
| Cemiplimab | Experimental | After inclusion, all patients will be treated with Cemiplimab 350mg intravenously every three weeks Receives: Drug: Cemiplimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR) after 24 weeks of cemiplimab
To evaluate the overall response rate (ORR) after 24 weeks of cemiplimab in secondary angiosarcomas, according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 or daylight photography as per WHO Offset Publication No. 48.
Measured: From the date of study inclusion until 24 weeks after inclusion. Interim analysis after 13 patients
Secondary outcomes (8)
Best Overall Response Rate
To establish the best ORR of patients with secondary angiosarcomas receiving cemiplimab
Measured: From the date of study inclusion to the end of the treatment period. Assessed up to 2 years after inclusion
Time to response and duration of response
To establish the median time to response (TTR) and duration of response (DOR) in patients with secondary angiosarcomas receiving cemiplimab.
Measured: From the date of study inclusion to the date of response or progression. Assessed up to 2 years after inclusion
Progression free survival (PFS)
To assess the median progression-free survival (PFS) of patients with secondary angiosarcomas receiving cemiplimab
Measured: Counting from the date of study inclusion to the date of progressive disease or death. Assessed up to 2 years after inclusion.
Overall survival (OS)
To establish the overall survival (OS) of patients with secondary angiosarcomas receiving cemiplimab
Measured: From the date of study inclusion to the date of death. If study medication is discontinued for any reason, survival follow-up takes place every 12 weeks, also assessed up to 2 years
Relation between tumor characteristics and response to treatment
To investigate possible relations between response to cemiplimab and tumor characteristics (i.e. PD-L1 expression, tumour infiltrating lymphocytes, MYC status and tumour mutational burden)
Measured: 2-3 years
Differences between UV associated and radiation induced secondary angiosarcomas
To assess differences in response to cemiplimab between UV associated and radiation induced secondary angiosarcomas
Measured: 2-3 years
Effect on tumor tissue
To assess effects of cemiplimab on tumor tissue by comparing pre- and post-treatment biopsies
Measured: At specific timepoints tumor biopsies and liquid biopsies will be obtained. Tumor biopsies will be obtained at baseline, after 12 weeks and (voluntary) at end of treatment
Adverse events and toxicity
To quantify toxicity during cemiplimab treatment
Measured: From the date of inclusion until the end of the study (by progression or at the end of the treatment period, up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2021
- Study start1 Jan 2022
- Primary completion9 Oct 2024
- Study completion18 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Secondary AngiosarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All patients included in this interventional single arm study will be treated with cemiplimab
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme Europe B.V.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04873375
- Sponsor's protocol ID
- 2020-005465-13
- Status last verified
- Jun 2024
- First submitted
- 26 Apr 2021
- Last updated
- 31 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cemiplimab Treatment in Patients with Locally Advanced and Metastatic Secondary Angiosarcomas
- ClinicalTrials.gov ID
- NCT04873375
- Acronym / sponsor ID
- 2020-005465-13
- Conditions
- Secondary Angiosarcoma, Locally Advanced Sarcoma, Metastasis
- Keywords
- Secondary Angiosarcoma, Cemiplimab, immunotherapy, Angiosarcoma, Sarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Genzyme Europe B.V.
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 9 Oct 2024 (actual)
- Study completion
- 18 Oct 2024 (actual)
- First posted
- 5 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Secondary angiosarcomas are aggressive mesenchymal tumors with a poor prognosis and limited therapeutic options. Recent studies conducted in patients with cutaneous squamous-cell carcinoma provide evidence that cemiplimab has the potential to be an effective treatment also for patients with secondary angiosarcomas.
The purpose of this study is to evaluate the overall response rate after 24 weeks of cemiplimab treatment in patients with locally advanced or metastatic secondary angiosarcomas.
The investigators hypothesis is that cemiplimab could be an effective treatment for patients diagnosed with locally advanced and metastatic secondary angiosarcomas.
Detailed description
Study design: A prospective, interventional, non-randomized, multicenter, phase II clinical trial.
Hypothesis:
Cemiplimab is registered for the use in patients with cutaneous squamous-cell carcinoma. In these patient groups cemiplimab showed impressive results. There are numerous similarities between cutaneous squamous-cell carcinoma and secondary angiosarcomas. Based on these similarities, including a complex genetic background, PD-L1 expression and MYC expression, the investigators hypothesize that cemiplimab might be an effective treatment for locally advanced and metastatic secondary angiosarcomas.
Primary Objective:
To evaluate the overall response rate (ORR) after 24 weeks of cemiplimab in secondary angiosarcomas, according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 or daylight photography as per WHO Offset Publication No. 48.
Secondary Objectives:
Secondary objectives include the establishment of the best ORR, median time to response, duration of response and progression free survival. The secondary objectives also comprise safety and toxicity quantification and to investigate the relation between response to cemiplimab and various tumor characteristics.
Study Population:
Patients eligible for inclusion are at least 18 years of age, with adequate organ function, who have a histologically confirmed diagnosis of progressive unresectable locally advanced or metastatic secondary angiosarcoma. Patients eligible are patients in the first line of treatment if they are unfit for chemotherapy and patients in advanced lines of systemic treatment. Major exclusion criteria include significant ongoing autoimmune disease that requires immunosuppressive treatment, prior treatment with immune checkpoint inhibitors, active uncontrolled infections or recent pneumonitis. All patients will provide Informed Consent prior to inclusion in the study and during the course of the trial, al relevant data will be stored in electronic Case Report Forms (eCRF).
Treatment Schedule:
After study inclusion, patients will be treated with Cemiplimab 350mg intravenously every three weeks. Patients will receive treatment until disease progression or discontinuation due to unacceptable toxic effects, withdrawal of consent or other reasons. The maximum treatment period will be two years, as is standard of care for patients treated with immunotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All patients included in this interventional single arm study will be treated with cemiplimab
| Arm | Type | Receives |
|---|---|---|
| Cemiplimab | Experimental | Drug: CemiplimabAfter inclusion, all patients will be treated with Cemiplimab 350mg intravenously every three weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Adult patient aged ≥ 18 years.
- Signed written informed consent.
- Histologically confirmed diagnosis of progressive unresectable locally advanced or metastatic secondary angiosarcoma.
- Patients in the first line of systemic treatment unfit for chemotherapy and patients in advanced lines of systemic treatment.
- Measurable disease per RECIST 1.1 or per physical examination / daylight photography (WHO Offset Publication No. 48) as determined by the investigator.
Key exclusion criteria (17 listed)
- Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs. The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 Diabetes mellitus, residual hypothyroidism that required only hormone therapy, or psoriasis that does not require systematic treatment.
- Prior treatment with immune checkpoint inhibitors.
- Continuous immunosuppressive corticosteroid treatment (doses > 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab. Note: patients who require a brief course of steroids (e.g. as prophylaxis for imaging studies) are not excluded.
- Active uncontrolled infection requiring therapy, including infection with HIV, active infection with HBV or HCV.
- History of pneumonitis within the last 5 years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CemiplimabAlso: LIBTAYOAfter inclusion patients will be treated with Cemiplimab 350mg intravenously every three weeks | Drug | Cemiplimab |
Primary outcome
Overall Response Rate (ORR) after 24 weeks of cemiplimab
Time frame: From the date of study inclusion until 24 weeks after inclusion. Interim analysis after 13 patients
To evaluate the overall response rate (ORR) after 24 weeks of cemiplimab in secondary angiosarcomas, according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 or daylight photography as per WHO Offset Publication No. 48.
8 secondary outcomes
Best Overall Response Rate
Time frame: From the date of study inclusion to the end of the treatment period. Assessed up to 2 years after inclusion
Time to response and duration of response
Time frame: From the date of study inclusion to the date of response or progression. Assessed up to 2 years after inclusion
Progression free survival (PFS)
Time frame: Counting from the date of study inclusion to the date of progressive disease or death. Assessed up to 2 years after inclusion.
Overall survival (OS)
Time frame: From the date of study inclusion to the date of death. If study medication is discontinued for any reason, survival follow-up takes place every 12 weeks, also assessed up to 2 years
Relation between tumor characteristics and response to treatment
Time frame: 2-3 years
Differences between UV associated and radiation induced secondary angiosarcomas
Time frame: 2-3 years
Effect on tumor tissue
Time frame: At specific timepoints tumor biopsies and liquid biopsies will be obtained. Tumor biopsies will be obtained at baseline, after 12 weeks and (voluntary) at end of treatment
Adverse events and toxicity
Time frame: From the date of inclusion until the end of the study (by progression or at the end of the treatment period, up to 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2024.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cemiplimab in people with Secondary Angiosarcoma and Locally Advanced Sarcoma, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) after 24 weeks of cemiplimab (time frame: From the date of study inclusion until 24 weeks after inclusion. Interim analysis after 13 patients). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2024.