The purpose of this Phase 1b study is to assess the safety and maximum tolerated dose (MTD) of Decitabine in combination with Gemcitabine among previously treated patients diagnosed with advanced pancreatic adenocarcinoma or sarcoma (soft tissue and bone).
The objectives of this study are to assess the safety and tolerability of the combination of Decitabine with Gemcitabine in previously treated patients with advanced pancreatic cancer and advanced sarcoma and to define the recommended Phase II dose and describe the dose-limiting toxicity of the combination of Decitabine with Gemcitabine. The preliminary efficacy parameters of the combination of Decitabine with Gemcitabine will be estimated in terms of response rate, disease control rate and progression-free survival.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Dose escalation starting at 0.1mg/kg, subcutaneously administered on twice weekly schedule for three weeks of a 28 day cycle. Dose Escalation Schedule Dose Level/Dose of Decitabine per cycle Level -2: 0.1 mg/kg SQ twice weekly for 1 week; Level -1: 0.1 mg/kg SQ twice weekly for 2 weeks; Level 1\*: 0.1 mg/kg SQ twice weekly for 3 weeks; Level 2: 0.2 mg/kg SQ twice weekly for 3 weeks; \*Starting Dose Level
Fixed infusion rate of 900 mg/m2, IV over 90 min, on Days, 1, 8 and 15 of a 28-day cycle. Dose Escalation Schedule Dose Level/Dose of Decitabine per cycle Level -2: 0.1 mg/kg SQ twice weekly for 1 week; Level -1: 0.1 mg/kg SQ twice weekly for 2 weeks; Level 1\*: 0.1 mg/kg SQ twice weekly for 3 weeks; Level 2: 0.2 mg/kg SQ twice weekly for 3 weeks; \*Starting Dose Level
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
Dose Limiting Toxicity - To examine the toxicity related to the therapy by measuring the number of treatment related adverse events in patients
Non-Hematologic - Any grade 3,4 solid organ toxicity not explainable by another cause in the opinion of the principal investigator
Time frame: All eligible patients that have initiated treatment will be considered evaluable for assessing adverse event rate(s) up to 30 days after the last date of any study therapy
Tumor Response Rate - Change at evaluations
Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) \[Eur J Ca 45:228-247, 2009\]. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.
Time frame: Change on two consecutive evaluations at least 8 weeks apart up to 30 days after the last date of any study therapy
Disease control rate (DCR)
DCR is defined as the proportion of patients who achieved a complete response (CR), partial response (PR) or stable disease (SD).
Time frame: Patients will be evaluated weekly during each cycle of treatment up to 30 days after the last date of any study therapy
Progression-free survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death due to any cause, whichever occurs first.
Time frame: Patients will be evaluated weekly during each cycle of treatment up to 30 days after the last date of any study therapy
Overall survival (OS)
OS is defined as the duration of time from start of treatment to death due to any cause.
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Time frame: Patients will be evaluated weekly during each cycle of treatment up to 30 days after the last date of any study therapy