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

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Kjetil Boye, Oslo University Hospital
Sponsor:
Collaborators:
Italian Sarcoma Group
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Kjetil Boye, Oslo University Hospital
ClinicalTrials.gov Identifier:
NCT03013127
First received: January 4, 2017
Last updated: May 30, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Osteosarcoma Drug: Pembrolizumab Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: PROMO: A Phase II Study of Pembrolizumab in Patients With Relapsed Or Metastatic Osteosarcoma Not Eligible for Curative Surgery

Resource links provided by NLM:


Further study details as provided by Kjetil Boye, Oslo University Hospital:

Primary Outcome Measures:
  • Clinical benefit rate [ Time Frame: At 18 weeks ]
    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.


Secondary Outcome Measures:
  • Overall response rate (ORR) [ Time Frame: Assessments every 6-9 weeks up to 2 years ]
    The percentage of patients with unresectable osteosarcoma who have achieved objective response during treatment; complete response (CR), partial response (PR), as assessed using RECIST v1.1.

  • Progression-free survival (PFS) [ Time Frame: Up to 4 years ]
  • Response rate by immune-related Response Criteria (ir-RC) [ Time Frame: Assessments every 6-9 weeks up to 2 years ]
  • Overall survival (OS) [ Time Frame: 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 [ Time Frame: Assessments every 6-9 weeks up to 2 years ]
    To evaluate the safety and tolerability of pembrolizumab in patients with osteosarcoma.

  • Health-related quality of life changes using EORTC QLQ-C30 [ Time Frame: Assessments every 6-9 weeks up to 4 years ]
    To evaluate health-related quality of life changes from baseline in patients with osteosarcoma, receiving pembrolizumab, using EORTC QLQ-C30.


Estimated Enrollment: 25
Anticipated Study Start Date: May 30, 2017
Estimated Study Completion Date: December 2023
Estimated Primary Completion Date: November 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pembrolizumab
Pembrolizumab (MK-3475) 200 mg i.v. every 3 weeks for up to 35 cycles
Drug: Pembrolizumab
Pembrolizumab is a humanized antibody used in cancer immunotherapy.
Other Name: Keytruda

Detailed Description:

Patients with osteosarcoma, who are not eligible for surgery of curative intent and have completed at least one line of systemic therapy, will be considered for treatment with pembrolizumab. Patients who are considered medically unfit for chemotherapy and where no other treatment options are believed to be of major benefit may also be considered. Patients will receive pembrolizumab for up to 35 cycles.

Patients, who have received 35 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 clinically meaningful response after 35 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 > 8 weeks after cycle 35.

Due to the low incidence of osteosarcoma, the inclusion rate is expected to be low, thus a Simon's two-stage design is suggested. Evaluation of efficacy and safety in stage one will be performed after the first 12 patients have been treated for 18 weeks:

  • In case of ≤2 responders; the trial ends.
  • If ≥3 responders, the trial will continue into stage II to a total number of 25 patients.
  Eligibility

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

Inclusion Criteria:

  1. Histologically confirmed osteosarcoma.
  2. Disease relapse or progression after at least one line of systemic treatment.

    1. First-line systemic treatment should include cytotoxic chemotherapy according to local practice.
    2. 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.
  3. Surgical resection with curative intent not possible.
  4. Be willing and able to provide written informed consent/assent for the trial.
  5. Be >18 years of age on day of signing informed consent.
  6. Have measurable disease based on RECIST, version 1.1.
  7. 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.
  8. Have a performance status of 0 or 1 on the ECOG Performance Scale.
  9. Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
  10. 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.
  11. 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.
  12. 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. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  5. Hypersensitivity to pembrolizumab or any of its excipients.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. Has known history of, or any evidence of active, non-infectious pneumonitis.
  12. Has an active infection requiring systemic therapy.
  13. 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.
  14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  15. 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.
  16. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  19. 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03013127

Contacts
Contact: Kjetil Boye, MD 22934000 ext +47 kjetil.boye@rr-research.no

Locations
Italy
Istituto Ortopedico Rizzoli Not yet recruiting
Bologna, Italy
Contact: Emanuela Palmerini, MD       emanuela.palmerini@ior.it   
Norway
Oslo University Hospital Recruiting
Oslo, Norway
Contact: Kjetil Boye, MD       kjetil.boye@rr-research.no   
Sponsors and Collaborators
Oslo University Hospital
Italian Sarcoma Group
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Kjetil Boye, MD Oslo University Hospital
  More Information

Responsible Party: Kjetil Boye, MD PhD, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT03013127     History of Changes
Other Study ID Numbers: MK3475-482
Study First Received: January 4, 2017
Last Updated: May 30, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Kjetil Boye, Oslo University Hospital:
Osteogenic Sarcoma
Osteosarcoma
Sarcoma, Osteogenic
Pembrolizumab
Immunotherapy

Additional relevant MeSH terms:
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Pembrolizumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on June 22, 2017