Malignant Peripheral Nerve Sheath Tumour (MPNST)Phase 2NCT02691026
A Study of Pembrolizumab in Patients With Malignant Peripheral Nerve Sheath Tumor (MPNST), Not Eligible for Curative Surgery
A Phase 2 study testing Pembrolizumab in people with Malignant Peripheral Nerve Sheath Tumour (MPNST), run by Oslo University Hospital at 1 site in Norway.
Trial summary
This is phase II, single arm, open-label, interventional trial of pembrolizumab (MK-3475) in subjects with metastatic or locally advanced/unresectable or metastatic malignant peripheral nerve sheath tumour (MPNST). The patients will be treated with pembrolizumab for up to 10 cycles. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Peripheral Nerve Sheath Tumour (MPNST)
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteNorway
- Study dates
- Jun 2016to Dec 2020
- 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
- Be willing and able to provide written informed consent/assent for the trial.
- Be 18 years of age on day of signing informed consent.
- Have measurable disease based on RECIST, version 1.1.
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.
- Be willing to provide tissue from a newly obtained core or excisional biopsy of benign neurofibromatosis lesion (NF1 patients only)
- Have a performance status of 0 or 1 on the ECOG Performance Scale.
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- Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Who cannot join
- Is currently participating and receiving 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.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
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- Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Study of Pembrolizumab in Patients With Malignant Peripheral Nerve Sheath Tumor (MPNST), Not Eligible for Curative Surgery
This is phase II, single arm, open-label, interventional trial of pembrolizumab (MK-3475) in subjects with metastatic or locally advanced/unresectable or metastatic malignant peripheral nerve sheath tumour (MPNST).
The patients will be treated with pembrolizumab for up to 10 cycles.
Primary objective is to evaluate the percentage of patients with curatively unresectable MPNST who have achieved clinical response; complete response (CR), partial response (PR), or stable disease (SD) at 18 weeks as assessed by the Investigator, by using RECIST, v1.1.
Read the detailed description
Patients with MPNST, who are not eligible for surgery of curative intent, will be considered for treatment with pembrolizumab. Patients will receive pembrolizumab treatment for up to 10 cycles. The patients must discontinue study treatment earlier (before 10 cycles of pembrolizumab) if they experience symptomatic deterioration attributed to disease progression, intolerable toxicity related to pembrolizumab, any medical condition that may jeopardize the patient's safety, use of other non-protocol anti-cancer therapy or pregnancy.
Patients who have received 10 cycles of pembrolizumab or discontinued study treatment of another reason than progression, will in the follow-up period be assessed for safety and treatment-related toxicity (for up to 90 days), progression and survival.
Patients who have achieved a clinical meaningful response after 10 cycles of pembrolizumab, defined as complete response (CR), partial response (PR), and stable disease (SD) assessed by the Investigator by using RECIST, v1.1, and have not experienced any clinically significant toxicity of study treatment, may be considered for reintroduction of pembrolizumab, if progression is detected after cycle 10.
Due to the low incidence of MPNST, the inclusion rate is expected to be low, thus a Simon's two-stage design is suggested (see Statistical Analysis Plans - Section 8.0).
Evaluation of efficacy and safety in stage one will be performed after the first 7 patient has been treated for 18 weeks: In case of no responders; the trial ends. If one or more responders, the trial will continue into stage two to a total number of 18 patients will be included.
- Being tested
- Pembrolizumab
- Keywords
- MPNST, Pembrolizumab
- Medical subject headings
- Neurofibrosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab | Experimental | 200 mg pembrolizumab, i.v. infusion every 3 weeks for up to 10 cycles Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients with at least stable disease after 18 weeks of treatment assessed by RECIST 1.1.
Measured: 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2016 (estimated)
- Study startJun 2016
- Primary completionDec 2020
- Study completionDec 2020
Why it stopped: Slow enrollment as a result of low incidence of MPNST and the COVID-19 pandemic.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Peripheral Nerve Sheath Tumour (MPNST)Studies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Tormod Kyrre Guren, Oslo University Hospital
- Investigators
- Tormod K Guren, MD, PhD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02691026
- Sponsor's protocol ID
- MK3475_MPNST
- Status last verified
- Jun 2021
- First submitted
- 4 Feb 2016
- Last updated
- 23 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Pembrolizumab in Patients With Malignant Peripheral Nerve Sheath Tumor (MPNST), Not Eligible for Curative Surgery
- ClinicalTrials.gov ID
- NCT02691026
- Acronym / sponsor ID
- MK3475_MPNST
- Keywords
- MPNST, Pembrolizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment as a result of low incidence of MPNST and the COVID-19 pandemic.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Jun 2016 (actual)
- Primary completion
- Dec 2020 (actual)
- Study completion
- Dec 2020 (actual)
- First posted
- 24 Feb 2016 (estimated)
- 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.
This is phase II, single arm, open-label, interventional trial of pembrolizumab (MK-3475) in subjects with metastatic or locally advanced/unresectable or metastatic malignant peripheral nerve sheath tumour (MPNST).
The patients will be treated with pembrolizumab for up to 10 cycles.
Primary objective is to evaluate the percentage of patients with curatively unresectable MPNST who have achieved clinical response; complete response (CR), partial response (PR), or stable disease (SD) at 18 weeks as assessed by the Investigator, by using RECIST, v1.1.
Detailed description
Patients with MPNST, who are not eligible for surgery of curative intent, will be considered for treatment with pembrolizumab. Patients will receive pembrolizumab treatment for up to 10 cycles. The patients must discontinue study treatment earlier (before 10 cycles of pembrolizumab) if they experience symptomatic deterioration attributed to disease progression, intolerable toxicity related to pembrolizumab, any medical condition that may jeopardize the patient's safety, use of other non-protocol anti-cancer therapy or pregnancy.
Patients who have received 10 cycles of pembrolizumab or discontinued study treatment of another reason than progression, will in the follow-up period be assessed for safety and treatment-related toxicity (for up to 90 days), progression and survival.
Patients who have achieved a clinical meaningful response after 10 cycles of pembrolizumab, defined as complete response (CR), partial response (PR), and stable disease (SD) assessed by the Investigator by using RECIST, v1.1, and have not experienced any clinically significant toxicity of study treatment, may be considered for reintroduction of pembrolizumab, if progression is detected after cycle 10.
Due to the low incidence of MPNST, the inclusion rate is expected to be low, thus a Simon's two-stage design is suggested (see Statistical Analysis Plans - Section 8.0).
Evaluation of efficacy and safety in stage one will be performed after the first 7 patient has been treated for 18 weeks: In case of no responders; the trial ends. If one or more responders, the trial will continue into stage two to a total number of 18 patients will be included.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Drug: Pembrolizumab200 mg pembrolizumab, i.v. infusion every 3 weeks for up to 10 cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Be willing and able to provide written informed consent/assent for the trial.
- Be 18 years of age on day of signing informed consent.
- Have measurable disease based on RECIST, version 1.1.
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.
- Be willing to provide tissue from a newly obtained core or excisional biopsy of benign neurofibromatosis lesion (NF1 patients only)
Key exclusion criteria (20 listed)
- Is currently participating and receiving 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.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
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 |
|---|---|---|
| PembrolizumabAlso: Keytruda | Drug | Pembrolizumab |
Primary outcome
Percentage of patients with at least stable disease after 18 weeks of treatment assessed by RECIST 1.1.
Time frame: 18 weeks
Results and safety
The study was stopped early (reason given: Slow enrollment as a result of low incidence of MPNST and the COVID-19 pandemic.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2021.
- Individual participant dataSharing planned: No
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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.
Tormod K Guren, MD, PhD principal investigator
Oslo University Hospital
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 Pembrolizumab in people with Malignant Peripheral Nerve Sheath Tumour (MPNST), run by Oslo University Hospital at 1 site in Norway.
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 10 inclusion and 20 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: stopped early, as of the sponsor's last update on 23 Jun 2021. 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 Norway. 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 was stopped early (reason given: Slow enrollment as a result of low incidence of MPNST and the COVID-19 pandemic.). Results are not available in the source record.
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?
Percentage of patients with at least stable disease after 18 weeks of treatment assessed by RECIST 1.1. (time frame: 18 weeks). 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 Jun 2021.