Pembrolizumab and Gemcitabine Chemotherapy in Leiomyosarcoma and Undifferentiated Pleomorphic Sar… (NCT03123276) | Clinical Trial Compass
CompletedPhase 1/2
Pembrolizumab and Gemcitabine Chemotherapy in Leiomyosarcoma and Undifferentiated Pleomorphic Sarcoma
United Kingdom25 participantsStarted 2017-11-29
Plain-language summary
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.
Who can participate
Age range18 Years – 99 Years
SexALL
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Inclusion criteria
✓. Have a histologically confirmed case of undifferentiated pleomorphic sarcoma or leiomyosarcoma and be willing to consent for archival tumour material to be requested for transfer to The Royal Marsden for future review.
✓. Have biopsiable disease and be willing to agree to a biopsy in order to permit acquisition of mandatory paired tumour biopsies done during screening and following 9 weeks of treatment for analysis of immunomodulation.
✓. Be willing and able to provide written informed consent/assent for the trial.
✓. Be over 18 years of age on day of signing informed consent.
✓. Have a performance status of 0 or 1 on the ECOG Performance Scale.
✓. Have measurable disease based on RECIST 1.1.
✓. Have a life expectancy of \>12 weeks
✓. Demonstrate adequate organ function as defined in the protocol, all screening labs should be performed within 28 days of treatment initiation.
Exclusion criteria
What they're measuring
1
Number of Patients With Dose Limiting Toxicities.
Timeframe: Treatment start date until completion of 1 full cycle of treatment (21 days)
. 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)
✕. 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.
✕. 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 carcinomatous 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 carcinomatous meningitis which is excluded regardless of clinical stability.