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OsteosarcomaPhase 2PROMONCT03013127

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

A Phase 2 study testing Pembrolizumab in people with Osteosarcoma, run by Oslo University Hospital at 2 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Osteosarcoma
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
12 participants
Where
2 sitesin 2 countries
Study dates
30 May 2017to 31 Jan 2019
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

  • 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.
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  • 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.

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)
  • 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.
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  • 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.
  • 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

2 sites in 2 countries.

2 sites in 2 countries

Italy1 site

  • Istituto Ortopedico Rizzoli

    Bologna

Other trials in Italy

Norway1 site

  • Oslo University Hospital

    Oslo

Other trials in Norway

About this study

Official title: PROMO: A Phase II Study of Pembrolizumab in Patients With Relapsed Or Metastatic Osteosarcoma Not Eligible for Curative Surgery

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.

Read the 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.
Conditions
Osteosarcoma
Being tested
Pembrolizumab
Keywords
Osteogenic Sarcoma, Osteosarcoma, Sarcoma, Osteogenic, Pembrolizumab, Immunotherapy
Medical subject headings
Osteosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called Keytruda

    Pembrolizumab is a humanized antibody used in cancer immunotherapy.

Study groups in NCT03013127
Study groupRoleWhat they receive
PembrolizumabExperimentalPembrolizumab (MK-3475) 200 mg i.v. every 3 weeks for up to 35 cycles
Receives: Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At 18 weeks

Secondary outcomes (6)

  1. Overall response rate (ORR)

    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.

    Measured: Assessments every 6-9 weeks up to 2 years

  2. Progression-free survival (PFS)

    Measured: Up to 4 years

  3. Response rate by immune-related Response Criteria (ir-RC)

    Measured: Assessments every 6-9 weeks up to 2 years

  4. Overall survival (OS)

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

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

    To evaluate the safety and tolerability of pembrolizumab in patients with osteosarcoma.

    Measured: Assessments every 6-9 weeks up to 2 years

  6. Health-related quality of life changes using EORTC QLQ-C30

    To evaluate health-related quality of life changes from baseline in patients with osteosarcoma, receiving pembrolizumab, using EORTC QLQ-C30.

    Measured: Assessments every 6-9 weeks up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jan 2017 (estimated)
  2. Study start30 May 2017
  3. Primary completion26 Nov 2018
  4. Study completion31 Jan 2019

Why it stopped: Inclusion of patients was stopped because ≤2 patients had clinical benefit.

Resources

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
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03013127
Sponsor's protocol ID
MK3475-482
Acronym
PROMO
Status last verified
Oct 2020
First submitted
4 Jan 2017
Last updated
14 Oct 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33580363

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab in people with Osteosarcoma, run by Oslo University Hospital at 2 sites in 2 countries.

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 14 inclusion and 21 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 14 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Italy, 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: Inclusion of patients was stopped because ≤2 patients had clinical benefit.). 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?

Clinical benefit rate (time frame: At 18 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03013127, which also lists 1 linked publication.

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 14 Oct 2020.

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