PROMO: A Phase II Study of Pembrolizumab in Patients With Relapsed Or Metastatic Osteosarcoma Not Eligible for Curative Surgery
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Osteosarcoma
- Sponsor
- Oslo University Hospital
- Enrollment
- 12
- Locations
- 2
- Primary Endpoint
- Clinical benefit rate
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
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.
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.
Investigators
Kjetil Boye
MD PhD
Oslo University Hospital
Eligibility Criteria
Inclusion Criteria
- •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.
- •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
- •Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen.
Exclusion Criteria
- •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.
Arms & Interventions
Pembrolizumab
Pembrolizumab (MK-3475) 200 mg i.v. every 3 weeks for up to 35 cycles
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
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 Outcomes
- Overall response rate (ORR)(Assessments every 6-9 weeks up to 2 years)
- Progression-free survival (PFS)(Up to 4 years)
- 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)
- Response rate by immune-related Response Criteria (ir-RC)(Assessments every 6-9 weeks up to 2 years)
- Health-related quality of life changes using EORTC QLQ-C30(Assessments every 6-9 weeks up to 4 years)
- Overall survival (OS)(Through study completion, up to 4 years after enrollment of last patient)