Decitabine and Gemcitabine for Pancreatic Cancer and Sarcoma

• ClinicalTrials.gov Identifier: NCT02959164
• Recruitment Status: Active, not recruiting
• First Posted: November 8, 2016
• Last Update Posted: August 23, 2022
• Sponsor: Varun Monga, MD
• Collaborators: Holden Comprehensive Cancer Center; University of Iowa
• Information provided by (Responsible Party): Varun Monga, MD, University of Iowa

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Pancreatic Ductal Adenocarcinoma; Sarcoma	Drug: Decitabine; Drug: Gemcitabine	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b Study: Treatment of Refractory Pancreatic Adenocarcinoma and Advanced Soft Tissue or Bone Sarcomas Using Decitabine Combined With Gemcitabine
• Study Start Date: December 2016
• Actual Primary Completion Date: September 30, 2019
• Estimated Study Completion Date: April 2023

Arms and Interventions

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 Name: 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 Name: Gemzar

Outcome Measures

Primary Outcome Measures :

1. Dose Limiting Toxicity - To examine the toxicity related to the therapy by measuring the number of treatment related adverse events in patients [ 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 ]
   Non-Hematologic - Any grade 3,4 solid organ toxicity not explainable by another cause in the opinion of the principal investigator
2. Tumor Response Rate - Change at evaluations [ Time Frame: Change on two consecutive evaluations at least 8 weeks apart up to 30 days after the last date of any study therapy ]

   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.

Secondary Outcome Measures :

1. Disease control rate (DCR) [ Time Frame: Patients will be evaluated weekly during each cycle of treatment up to 30 days after the last date of any study therapy ]
   DCR is defined as the proportion of patients who achieved a complete response (CR), partial response (PR) or stable disease (SD).
2. Progression-free survival (PFS) [ Time Frame: Patients will be evaluated weekly during each cycle of treatment up to 30 days after the last date of any study therapy ]
   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.
3. Overall survival (OS) [ Time Frame: Patients will be evaluated weekly during each cycle of treatment up to 30 days after the last date of any study therapy ]
   OS is defined as the duration of time from start of treatment to death due to any cause.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Iowa

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States, 52242

Sponsors and Collaborators

Varun Monga, MD

Holden Comprehensive Cancer Center

University of Iowa

Investigators

• Principal Investigator: Varun Monga, MD; University of Iowa

  Study Documents (Full-Text)

Documents provided by Varun Monga, MD, University of Iowa:

Informed Consent Form  [PDF] October 10, 2019

More Information

• Responsible Party: Varun Monga, MD, Clinical Assistant Professor, University of Iowa
• ClinicalTrials.gov Identifier: NCT02959164
• Other Study ID Numbers: 201610750
• First Posted: November 8, 2016
• Last Update Posted: August 23, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Adenocarcinoma; Sarcoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective and Soft Tissue; Gemcitabine; Decitabine; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Enzyme Inhibitors