Pembrolizumab and Gemcitabine Chemotherapy in Leiomyosarcoma and Undifferentiated Pleomorphic Sarcoma

Sponsor
Royal Marsden NHS Foundation Trust
Study ID
NCT03123276
Phase
PHASE1/PHASE2
Status
Completed

Conditions

  • Sarcoma

Eligibility Criteria

Sex
ALL
Age
18 Years - 99 Years
Healthy Volunteers
Not accepted

Interventions

  • Pembrolizumab — DRUG
    humanized IgG4 PD-1 blocking antibody
  • Gemcitabine — DRUG
    Doses of 800, 1000 and 1200 mg/m2 will be used in dose escalation phase.

Study Details

Soft tissue sarcomas (STS) are a group of rare mesenchymal neoplasms affecting all ages. STS most commonly present as localised disease but despite surgery and adjuvant treatment more than half of patients will develop recurrent or metastatic disease. Leiomyosarcoma (LMS), a malignancy of smooth muscle, is one of the most common STS and undifferentiated pleomorphic sarcoma (UPS) is a common sarcoma sub-type with aggressive symptoms. Recent studies have demonstrated reasonable sensitivity of LMS to gemcitabine monotherapy with an objective response rate of 8-19%. However the overall survival is still only about 12 months which illustrates the critical clinical need for improved therapies for advanced STS and sarcoma in general. In this study the investigators propose to combine the immune synapse checkpoint inhibitor with the cytotoxic and immune modulating agent, gemcitabine. It is hoped that this dual immunomodulatory approach will enhance the effect of pembrolizumab on PD-L1 expressing LMS and UPS, leading to a safe treatment with patient outcomes. This is a two part, phase I, single centre dose escalation and dose expansion study in the total of 24 patients with newly diagnosed metastatic or inoperable LMS and UPS. There will be approximately 12 patients in the dose escalation cohort (part A) and the starting dose will be a fixed dose rate (FDR) gemcitabine of 800 mg/m2 on day 1 and 8 of 21 days cycles in combination of 200 mg of pembrolizumab given as an infusion on day 1 every 3 weeks. The MTD cohort (part B) will then be expanded to a total of 12 patients in order to further evaluate the safety and tolerability of that dose as well as to preliminarily assess response to therapy. The study is sponsored by Royal Marsden NHS Foundation trust and the funding for the study is provided by Merck Sharp \& Dohme Limited.

Key Dates

Start date
Nov 29, 2017
Status verified
Feb 2026
Primary completion
May 20, 2022
Completion
May 20, 2022

Study Design

Enrollment
25 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER

Arms

  • Experimental: gemcitabine + pembrolizumab
    First cohort of 6 patients may receive Gemcitabine 800 mg/m2 + Pembrolizumab 200 mg. After safety data review, if no DLTs then dose for Gemcitabine will be increased to 1000 and further 1200 mg/m2.

Primary Outcome Measure

Number of Patients With Dose Limiting Toxicities. [ Time Frame: Treatment start date until completion of 1 full cycle of treatment (21 days) ]

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