Malignant Mesothelioma (MPM)Phase 1/2NCT03399552
Stereotactic Body Radiation Therapy and Avelumab Immunotherapy for Treatment of Malignant Mesothelioma
A Phase 1/2 study testing Avelumab and Stereotactic Body Radiation Therapy in people with Malignant Mesothelioma (MPM), run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
Trial summary
The purpose of this study is to find out whether the combination of avelumab and SBRT is safe and what effect avelumab has on mesothelioma when given in combination with SBRT. In addition, a goal of this protocol is to study the effect of radiation therapy on the immune system. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Mesothelioma (MPM)
- What is being tested?
- Avelumab and Stereotactic Body Radiation Therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 7 sitesUnited States
- Study dates
- 20 Dec 2017to 20 Jan 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patient willing and able to provide written informed consent for the trial.
- Patient age ≥ 18 at time of consent.
- Histologically or cytologically confirmed malignant pleural or peritoneal mesothelioma (MPM).
- No plans for surgical resection.
- At least one prior line of systemic therapy. Note: Patients on prior immunotherapy are eligible.
- At least one targetable lesion appropriate for palliative SBRT and one non-target lesion
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- Karnofsky Performance Score (KPS) ≥ 70%
- If of childbearing potential, must be willing to use highly effective mode of contraception for at least one month prior, during, and for 2 months after the end of active therapy
- Adequate organ function, defined as:
- Absolute Neutrophil Count ≥ 1.5K/mcL.
- Platelet count ≥ 100K/mcL.
- Adequate renal function as defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula or serum creatinine ≤ 1.5 x ULN
- Hemoglobin > 9g/dL (prior transfusion permitted)
- Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range
- AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
- If the patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
Who cannot join
- Currently participating and receiving another study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Prior radiation therapy precluding SBRT
- Continuous oxygen use
- Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
- Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
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- Patient who rapidly progressed on prior immunotherapy, as determined by the treating physician, are not eligible.
- Prior Therapies:
- Treatment with a monoclonal antibody within 4 weeks prior to study Day 1 or has not recovered (i.e., ≥ Grade 1 at baseline) from adverse events due to agents administered
- Prior chemotherapy, targeted small molecule therapy, within 4 weeks prior to study Day 1 or has not recovered (i.e., ≥ Grade 1 at baseline) from adverse events due to a previously administered agent (excluding Grade 2 neuropathy).
- Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti- Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) within 4 weeks prior to study Day 1 or has not recovered (i.e., >/= Grade 1 at baseline) from adverse events
- Comorbidities or Prior Conditions:
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Prior organ transplantation including allogenic stem-cell transplantation.
- Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
- Known history of active TB (Tuberculosis).
- Known history of HIV or known acquired immunodeficiency syndrome.
- Active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection at screening or positive serologies indicating prior infection.
- Active infection requiring systemic therapy.
- Evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- Pregnant women or women who are breastfeeding or of childbearing potential and not using a highly effective method of birth control for at least one month prior to enrollment. If the risk of contraception exists, male and female subjects must use highly effective contraception throughout the study and for at least 60 days after last avelumab treatment.
- Highly effective contraception includes either 2 barrier methods (diaphragm, condom by the partner, copper intrauterine device, sponge, or spermicide), or 1 barrier method and 1 hormonal method (any oral, subcutaneous, intrauterine, or intramuscular registered and marketed contraceptive agent that contains an estrogen and/or a progesterone agent).
- Vaccination within 4 weeks prior to the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines.
- Concomitant use of the following medications
- Any investigational anticancer therapy.
- Any concurrent chemotherapy, immunotherapy, or biologic therapy. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable.
- Immunosuppressive medications including, but not limited to systemic corticosteroids (>10 mg/day prednisone or equivalent), methotrexate, azathioprine, and tumor necrosis factor alpha (TNF-α) blockers. Use of immunosuppressive medications for the management of investigational product-related AEs, in subjects with contrast allergies is acceptable. In addition, use of inhaled and intranasal corticosteroids is permitted.
- Known contraindications to radiotherapy
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Memorial Sloan Kettering at Basking Ridge
Basking Ridge, New Jersey, 07920
Memorial Sloan Kettering Commack
Commack, New York, 11725
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Sloan Kettering Rockville Centre
Rockville Centre, New York, 11570
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
About this study
Official title: An Efficacy and Safety Study of Avelumab Plus SBRT in Malignant Mesothelioma (MPM)
The purpose of this study is to find out whether the combination of avelumab and SBRT is safe and what effect avelumab has on mesothelioma when given in combination with SBRT. In addition, a goal of this protocol is to study the effect of radiation therapy on the immune system. It is thought that radiation treatment may create a form of 'vaccine' against cancer inside the body and immunotherapy may improve this effect. The combination of radiation treatment and immunotherapy may be more effective against cancer than either radiation or immunotherapy alone.
- Conditions
- Malignant Mesothelioma (MPM)
- Being tested
- Avelumab, Stereotactic Body Radiation Therapy
- Keywords
- Stereotactic Body Radiation Therapy, Avelumab Immunotherapy, 17-358
- Medical subject headings
- Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvelumabDrug
10mg/kg delivered by IV infusion
Stereotactic Body Radiation TherapyRadiation
short course of SBRT after the first two doses of avelumab
| Study group | Role | What they receive |
|---|---|---|
| Avelumab | Experimental | The treatment will consist of one dose of avelumab every other week as well as a short course of SBRT after the first two doses of avelumab. Receives: Drug: Avelumab; Radiation: Stereotactic Body Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
defined by modified RECIST 1.1 for mesothelioma
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2018
- Study start20 Dec 2017
- Primary completion20 Jan 2023
- Study completion20 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malignant Mesothelioma (MPM)Studies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a single-arm, two-stage study that will be conducted at Memorial Sloan Kettering Cancer Center Main Campus and regional sites.
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Andreas Rimner, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03399552
- Sponsor's protocol ID
- 17-358
- Status last verified
- Jan 2023
- First submitted
- 9 Jan 2018
- Last updated
- 23 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Efficacy and Safety Study of Avelumab Plus SBRT in Malignant Mesothelioma (MPM)
- ClinicalTrials.gov ID
- NCT03399552
- Acronym / sponsor ID
- 17-358
- Conditions
- Malignant Mesothelioma (MPM)
- Keywords
- Stereotactic Body Radiation Therapy, Avelumab Immunotherapy, 17-358
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 20 Dec 2017 (actual)
- Primary completion
- 20 Jan 2023 (actual)
- Study completion
- 20 Jan 2023 (actual)
- First posted
- 16 Jan 2018 (actual)
- Results
- Posted 23 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out whether the combination of avelumab and SBRT is safe and what effect avelumab has on mesothelioma when given in combination with SBRT. In addition, a goal of this protocol is to study the effect of radiation therapy on the immune system. It is thought that radiation treatment may create a form of 'vaccine' against cancer inside the body and immunotherapy may improve this effect. The combination of radiation treatment and immunotherapy may be more effective against cancer than either radiation or immunotherapy alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single-arm, two-stage study that will be conducted at Memorial Sloan Kettering Cancer Center Main Campus and regional sites.
| Arm | Type | Receives |
|---|---|---|
| Avelumab | Experimental | Drug: Avelumab, Radiation: Stereotactic Body Radiation TherapyThe treatment will consist of one dose of avelumab every other week as well as a short course of SBRT after the first two doses of avelumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patient willing and able to provide written informed consent for the trial.
- Patient age ≥ 18 at time of consent.
- Histologically or cytologically confirmed malignant pleural or peritoneal mesothelioma (MPM).
- No plans for surgical resection.
- At least one prior line of systemic therapy. Note: Patients on prior immunotherapy are eligible.
Key exclusion criteria (29 listed)
- Currently participating and receiving another study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Prior radiation therapy precluding SBRT
- Continuous oxygen use
- Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
- Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
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 |
|---|---|---|
| Avelumab10mg/kg delivered by IV infusion | Drug | Avelumab |
| Stereotactic Body Radiation Therapyshort course of SBRT after the first two doses of avelumab | Radiation | Avelumab |
Primary outcome
Overall Response Rate
Time frame: 3 years
defined by modified RECIST 1.1 for mesothelioma
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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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.
Andreas Rimner, MD principal investigator
Memorial Sloan Kettering Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Avelumab and Stereotactic Body Radiation Therapy in people with Malignant Mesothelioma (MPM), run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
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 16 inclusion and 29 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 23 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 23 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 (time frame: 3 years). 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 23 Oct 2023.