Pembrolizumab and Gemcitabine Chemotherapy in Leiomyosarcoma and Undifferentiated Pleomorphic Sarcoma (GEMMK)
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|ClinicalTrials.gov Identifier: NCT03123276|
Recruitment Status : Recruiting
First Posted : April 21, 2017
Last Update Posted : September 19, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Sarcoma||Drug: Pembrolizumab Drug: Gemcitabine||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study to Assess the Safety and Tolerability of Pembrolizumab in Combination With Fixed Rate Gemcitabine Chemotherapy in Patients With Leiomyosarcoma and Undifferentiated Pleomorphic Sarcoma|
|Actual Study Start Date :||November 29, 2017|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2019|
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.
humanized IgG4 PD-1 blocking antibody
Other Name: Keytruda
Doses of 800, 1000 and 1200 mg/m2 will be used in dose escalation phase.
- Maximum tolerated dose of gemcitabine that can be safely combined with pembrolizumab in the absence of dose limiting toxicities. [ Time Frame: completion of 1 full cycle of treatment (21 days) ]primary outcome
- Immunophenotyping of biopsies (FFPE samples, density and phenotype of tumour infiltrating lymphocytes; CD3+, CD8+, CD45, FoxP3 and PD1) [ Time Frame: Pre and post-treatment (9 weeks after end of treatment) ]Secondary outcome
- Location of tumour infiltrating lymphocytes (proximity to tumour cells and location relative to the microvasculature; Prototype analysis software at ICR) [ Time Frame: Up to 18 months from the first dose administered ]Secondary outcome
- Response stratification according to tumour PD-L1 expression [ Time Frame: 6 and 12 months ]Secondary outcome
- preliminary evaluation of response by using RECIST v1.1 [ Time Frame: 2 months after the last dose ]Secondary outcome
- Identify bio-markers and correlate with clinical benefit, as defined by RECIST v1.1 [ Time Frame: Up to 18 months from the first dose administered ]Exploratory outcome
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03123276
|Contact: Dale Smithfirstname.lastname@example.org|
|Contact: Victoria Pittordouemail@example.com|
|London, United Kingdom|
|Contact: Robin Jones firstname.lastname@example.org|
|Principal Investigator:||Robin Jones||Royal Marsden NHS Foundation Trust|