Clinical trial NCT02959164: Decitabine and Gemcitabine for Pancreatic Cancer and Sarcoma
Official title: A Phase 1b Study: Treatment of Refractory Pancreatic Adenocarcinoma and Advanced Soft Tissue or Bone Sarcomas Using Decitabine Combined With Gemcitabine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Ductal Adenocarcinoma
Sarcoma
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: Holden Comprehensive Cancer Center
name: University of Iowa
First posted: 2016-11-08
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: Dose Limiting Toxicity - To examine the toxicity related to the therapy by measuring the number of treatment related adverse events in patients
timeFrame: 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
measure: Tumor Response Rate - Change at evaluations
timeFrame: Change on two consecutive evaluations at least 8 weeks apart up to 30 days after the last date of any study therapy
Secondary outcomes:
measure: Disease control rate (DCR)
timeFrame: Patients will be evaluated weekly during each cycle of treatment up to 30 days after the last date of any study therapy
measure: Progression-free survival (PFS)
timeFrame: Patients will be evaluated weekly during each cycle of treatment up to 30 days after the last date of any study therapy
measure: Overall survival (OS)
timeFrame: Patients will be evaluated weekly during each cycle of treatment up to 30 days after the last date of any study therapy
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
Study officials:
affiliation: University of Iowa
name: Mohammed Milhem, MD
role: PRINCIPAL_INVESTIGATOR
References: