Clinical trial NCT02417753
Conditions: Ovarian Cancer Ovarian Neoplasms Ascites Gastrointestinal Cancer Gastrointestinal Neoplasms
Keywords: PARACENTESIS STAT3 Antisense Oligonucleotide Ascites AZD9150 Surgical Resection
Sponsor: National Cancer Institute (NCI)
Start date: 2015-04-03; Completion date: 2016-04-07
Enrollment: 1 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Background:

\- Some people with gastrointestinal or ovarian cancer also have ascites. That is free fluid built up in the abdomen. Researchers want to see if a new drug can affect some of the immune cells in the ascites. This may also treat the cancer.

Objective:

\- To look at the immune markers the ascites of people with gastrointestinal or ovarian cancer.

Eligibility:

\- Adults age 18 and older with a malignancy of the gastrointestinal tract (GI) tract or metastatic ovarian cancer. As a result, they have ascites in the abdomen.

Design:

* Participants will be screened with:
* Medical history, physical exam, and blood tests.
* Echocardiogram: sound waves make images of the heart.
* Electrocardiogram: measures electrical activity of the heart.
* Paracentesis: a needle will be inserted in the abdomen and will remove some of the ascites fluid.
* They may have a tumor biopsy.
* Participants will get AZD9150 through a vein for 3 hours. They will get this 6 times in cycle 1 and 4 times all other cycles. Each cycle is 28 days.
* Each cycle, participants will:
* Have a physical exam.
* Have blood tests weekly.
* Be asked about how they feel and any medicines they are taking.
* After every 2 cycles (about every 2 months), participants will have scans and x-rays of their tumor.
* Participants will have paracentesis 2 more times during the study. They will have another echocardiogram.
* At the end of therapy, participants will have a physical exam and blood tests. They will be asked about how they feel and any medicines they are taking.

Detailed description:
Background:

* Signal transducer and activator of transcription 3 (STAT)3 is considered to be a promising cancer drug target because of its pleiotropic involvement in tumorigenesis. STAT3 not only regulates the expression of many genes which are directly important for the survival of tumor cells, but it is also an important factor in non-tumor cells in the tumor microenvironment involved in immune evasion of tumor cells, angiogenesis, and metastasis.
* AZD9150 is an antisense oligonucleotide designed to target and down-regulate expression of human STAT3 mRNA.
* By focusing on patients with malignant ascites it will be more feasible for us to sample the tumor environment and to do it more frequently than, for example, conventional tumor tissue biopsies. Malignant ascites is a relatively common occurrence in ovarian and gastrointestinal malignancies, impacting greatly on quality of life.

Objectives:

-To measure changes in immune parameters in the malignant ascites of patients with advanced cancer following therapy with AZD9150.

Select Eligibility:

* Age greater than or equal to 18 years.
* Histologically confirmed metastatic ovarian or GI malignancy with malignant ascites. Patients must have ascites amenable for paracentesis.
* Patient that have relapsed or have been refractory to at least one prior chemotherapy regimen, or patients for whom no standard therapy exists

Design:

* Up to N=15 eligible patients will receive AZD9150 at the following schedule:

  * Cycle 1 only: AZD9150 will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22.
  * Cycle 2 and beyond: AZD9150 will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle.
* Patients will be re-staged every 8 weeks.
* Patients will undergo a baseline pretreatment paracentesis which will be repeated on Cycle 1 Days 8 and 15. An optional paracentesis may be attempted on D57 or off treatment (whichever happens first). Immune subsets analysis at baseline in biopsy/ascites/peripheral blood mononuclear cells (PBMC) and post AZD9150 in surgical specimen, ascites and PBMC will be analyzed. STAT3 activation status will also be assessed in tumor cells isolated from malignant ascites at various time points.

Arms: arm 1: AZD9150 over a 28 day cycle
Interventions: intervention 1: AZD9150
Intervention descriptions: intervention 1: AZD9150 IV infusion over 3 hours Cycle 1: days 1, 3, 5, 8, 15 and 22 of a 28 day cycle. Cycle 2 and beyond Days 1, 8, 15 and 22 of a 28 day cycle

Protocol documents: