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A Study of Pembrolizumab in Patients With Malignant Peripheral Nerve Sheath Tumor (MPNST), Not Eligible for Curative Surgery

This study is currently recruiting participants.
Verified October 2017 by Tormod Kyrre Guren, Oslo University Hospital
Sponsor:
ClinicalTrials.gov Identifier:
NCT02691026
First Posted: February 24, 2016
Last Update Posted: October 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Tormod Kyrre Guren, Oslo University Hospital
  Purpose

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.


Condition Intervention Phase
Malignant Peripheral Nerve Sheath Tumour (MPNST) Drug: Pembrolizumab Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Pembrolizumab in Patients With Malignant Peripheral Nerve Sheath Tumor (MPNST), Not Eligible for Curative Surgery

Resource links provided by NLM:


Further study details as provided by Tormod Kyrre Guren, Oslo University Hospital:

Primary Outcome Measures:
  • Percentage of patients with at least stable disease after 18 weeks of treatment assessed by RECIST 1.1. [ Time Frame: 18 weeks ]

Estimated Enrollment: 18
Study Start Date: June 2016
Estimated Study Completion Date: December 2025
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pembrolizumab
200 mg pembrolizumab, i.v. infusion every 3 weeks for up to 10 cycles
Drug: Pembrolizumab
Other Name: Keytruda

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.

  Eligibility

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Be willing and able to provide written informed consent/assent for the trial.
  2. Be 18 years of age on day of signing informed consent.
  3. Have measurable disease based on RECIST, version 1.1.
  4. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.
  5. Be willing to provide tissue from a newly obtained core or excisional biopsy of benign neurofibromatosis lesion (NF1 patients only)
  6. Have a performance status of 0 or 1 on the ECOG Performance Scale.
  7. Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
  8. 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.
  9. 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.
  10. 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.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. Has a known history of active TB (Bacillus Tuberculosis)
  4. Hypersensitivity to pembrolizumab or any of its excipients.
  5. 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.
  6. 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.

    • 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.
  7. 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.
  8. 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.
  9. 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.
  10. Has known history of, or any evidence of active, non-infectious pneumonitis.
  11. Has an active infection requiring systemic therapy.
  12. 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.
  13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  14. 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.
  15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  18. 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02691026


Contacts
Contact: Tormod K Guren, MD, PhD 22935175 ext +47 uxtour@ous-hf.no

Locations
Norway
Oslo university Hospital Recruiting
Oslo, Norway, N-0424 Oslo
Contact: Tormod K Guren, Md, PhD    22935175 ext +47    uxtour@ous-hf.no   
Principal Investigator: Tormod K Guren, MD, PhD         
Sponsors and Collaborators
Oslo University Hospital
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Tormod K Guren, MD, PhD Oslo University Hospital
  More Information

Responsible Party: Tormod Kyrre Guren, MD, PhD, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT02691026     History of Changes
Other Study ID Numbers: MK3475_MPNST
First Submitted: February 4, 2016
First Posted: February 24, 2016
Last Update Posted: October 17, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Tormod Kyrre Guren, Oslo University Hospital:
MPNST
Pembrolizumab

Additional relevant MeSH terms:
Neurilemmoma
Nerve Sheath Neoplasms
Neurofibroma
Neurofibrosarcoma
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neuroma
Fibrosarcoma
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Pembrolizumab
Antineoplastic Agents