A Study of Pembrolizumab in Patients With Relapsed Or Metastatic Osteosarcoma Not Eligible for Curative Surgery

NCT03013127 | Terminated Phase 2

• 1 other identifier: MK3475-482
• Study Type: interventional
• Target: 12
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a phase II, single arm, open-label, interventional trial of pembrolizumab (MK-3475) in patients with osteosarcoma who have experienced disease relapse or progression after at least one line of systemic treatment, and who are not eligible for curative surgery.

Conditions

Osteosarcoma

Keywords

Osteogenic Sarcoma; Osteosarcoma; Sarcoma, Osteogenic; Pembrolizumab; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Clinical benefit rate

  The percentage of patients with unresectable osteosarcoma who have achieved clinical response; complete response (CR), partial response (PR), or stable disease (SD) at 18 weeks as assessed using RECIST v1.1.

  At 18 weeks

Secondary Outcomes (6)

• Overall response rate (ORR)

  Assessments every 6-9 weeks up to 2 years

• Progression-free survival (PFS)

  Up to 4 years

• Response rate by immune-related Response Criteria (ir-RC)

  Assessments every 6-9 weeks up to 2 years

• Overall survival (OS)

  Through study completion, up to 4 years after enrollment of last patient

• Number and type of Adverse Events related to pembrolizumab treatment in osteosarcoma patients as assessed by CTCAE v4.0

  Assessments every 6-9 weeks up to 2 years

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Pembrolizumab (MK-3475) 200 mg i.v. every 3 weeks for up to 35 cycles

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Pembrolizumab is a humanized antibody used in cancer immunotherapy.

Also known as: Keytruda

Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed osteosarcoma.
• Disease relapse or progression after at least one line of systemic treatment.
• First-line systemic treatment should include cytotoxic chemotherapy according to local practice.
• The patient can be eligible if he/she is considered medically unfit for chemotherapy, as assessed by the sarcoma centre in charge of the patient's treatment.
• Surgical resection with curative intent not possible.
• 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. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• 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.

You may not qualify if:

• 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)
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• 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.
• 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 sarcomatous 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 sarcomatous 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.

Sponsors & Collaborators

• Oslo University Hospital: lead
• Italian Sarcoma Group: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Istituto Ortopedico Rizzoli

Bologna, Italy

Location

Oslo University Hospital

Oslo, Norway

Location

Related Publications (1)

• Boye K, Longhi A, Guren T, Lorenz S, Naess S, Pierini M, Taksdal I, Lobmaier I, Cesari M, Paioli A, Londalen AM, Setola E, Hompland I, Meza-Zepeda LA, Sundby Hall K, Palmerini E. Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. Cancer Immunol Immunother. 2021 Sep;70(9):2617-2624. doi: 10.1007/s00262-021-02876-w. Epub 2021 Feb 12.

  PMID: 33580363 DERIVED

MeSH Terms

Conditions

Osteosarcoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Study Officials

• Kjetil Boye, MD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 4, 2017
• First Posted: January 6, 2017
• Study Start: May 30, 2017
• Primary Completion: November 26, 2018
• Study Completion: January 31, 2019
• Last Updated: October 14, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); NO (1)