Decitabine and Gemcitabine for Pancreatic Cancer and Sarcoma

A Phase 1b Study: Treatment of Refractory Pancreatic Adenocarcinoma and Advanced Soft Tissue or Bone Sarcomas Using Decitabine Combined With Gemcitabine

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).

Study Overview

• Status: Completed
• Conditions: Sarcoma; Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: Decitabine; Drug: Gemcitabine

Detailed Description

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
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients must have metastatic histologically or cytologically confirmed pancreatic adenocarcinoma or sarcoma (soft tissue or bone). Patient may enroll if he or she refuses first line therapy.
2. Age ≥18 years.
3. ECOG performance status ≤2 (Karnofsky ≥60% (See Appendix 1).
4. Life expectancy of greater than 3 months (does not apply to pancreatic cancer population).
5. Measureable disease per RECIST criteria.

6. Patients must have normal organ and marrow function as defined below:

   • Absolute neutrophil count ≥1,500/mm3
   • Platelets ≥100 k/mm3
   • Total bilirubin within normal institutional limits
   • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
   • Creatinine </= 1.5 ULN

7. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) from time of consent and for the duration of study participation as well as for 3 months after the completion of study drug. Adequate contraception consists of a double method of contraception, one method of which must be a barrier method.

   WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months).

   If a woman (or a male subject's female partner) becomes pregnant or suspects she is pregnant while she is participating in this study, she should inform her treating physician immediately.

8. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Chemotherapy or radiotherapy within 4 weeks (for targeted therapies 5 half-lives) prior to entering the study or failure to recover from adverse events due to agents administered to </= grade 1 or stable grade 2, at the discretion of the treating physician.
2. Patients who are receiving any other investigational agents.
3. Known brain metastases.
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Decitabine or other agents used in study.
5. Prior Decitabine for the treatment of this cancer. Patients with previous exposure to therapy with Gemcitabine are allowed in the study.
6. Pregnant or breast feeding women are excluded from participating in this study. WOCBP must have a negative serum pregnancy test within 7 days of the first administration of Decitabine.
7. Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required.
8. Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent.
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Decitabine and Gemcitabine; Decitabine, Dose escalation starting at 0.1mg/kg, subcutaneously administered on twice weekly schedule for three weeks of a 28 day cycle. Gemcitabine fixed infusion rate of 900 mg/m2, IV over 90 min, on Days, 1, 8 and 15 of a 28-day cycle.

Drug: Decitabine; 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; Other Names: Dacogen; Drug: Gemcitabine; 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; Other Names: Gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Change on two consecutive evaluations at least 8 weeks apart up to 30 days after the last date of any study therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	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.	Patients will be evaluated weekly during each cycle of treatment up to 30 days after the last date of any study therapy

Collaborators and Investigators

• Sponsor: Mohammed Milhem
• Collaborators: University of Iowa; Holden Comprehensive Cancer Center
• Investigators: Principal Investigator: Mohammed Milhem, MD, University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2016
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): October 16, 2020

Study Registration Dates

• First Submitted: November 6, 2016
• First Submitted That Met QC Criteria: November 7, 2016
• First Posted (Estimated): November 8, 2016

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Sarcoma; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine; Gemcitabine
• Other Study ID Numbers: 201610750

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No