AZD9150, a STAT3 Antisense Oligonucleotide, in People With Malignant Ascites

NCT02417753 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 15011215-C-0112
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Cancer; Ovarian Neoplasms; Ascites; Gastrointestinal Cancer; Gastrointestinal Neoplasms

Keywords

PARACENTESIS; STAT3 Antisense Oligonucleotide; Ascites; AZD9150; Surgical Resection

Outcome Measures

Primary Outcomes (1)

• Changes in Immune Parameters in the Malignant Ascites of Patients With Advanced Cancer Following Therapy With AZD9150

  Participants were to undergo research paracentesis. Ascitic fluid was to be obtained and processed for changes in the percentages of memory cluster of differentiation 8 (CD8) + cells, regulatory T cells, plasmacytoid dendritic cell (pDC), B cells and natural killer (NK) cells will be analyzed by flow cytometry.

  1.5 years

Secondary Outcomes (6)

• Effect on Signal Transducer and Activator of Transcription 3(STAT3)-Dependent & Associated Signaling Both in Tumor Cells, Peripheral Blood and the Microenvironment, Including Modulations in Chemokine and Cytokine Response Following Treatment With AZD9150

  1.5 years

• Reduction in Tyrosine-phosphorylated Signal Transducer and Activator of Transcription 3 (STAT3) Phospho- Signal Transducer and Activator of Transcription 3 (p- STAT3) Expression, Comparing Before and After Therapy, in Ascites and Peripheral Blood

  1.5 years

• Response Rate (RR) in Patients With Malignant Ascites Treated With AZD9150

  1.5 years

• Count of Participants With Serious and Non Serious Adverse Events

  4 months and 15 days

• Progression Free Survival (PFS) in Patients With Malignant Ascites Treated With AZD9150

  1.5 years

Study Arms (1)

AZD9150 in People with Malignant Ascites

EXPERIMENTAL

AZD9150 over a 28 day cycle

Drug: AZD9150

Interventions

AZD9150 DRUG

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

AZD9150 in People with Malignant Ascites

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed gastrointestinal (G)I malignancies or ovarian cancer prior to entering this study.
• Histologically confirmed metastatic ovarian or GI malignancy with malignant ascites amenable for paracentesis. Adjudication of malignant ascites can be made on clinical grounds e.g. in the absence of cirrhosis or other non-malignant causes of ascites.
• Patients who have relapsed or are refractory to at least one prior chemotherapy regimen, and for whom no standard therapy exists. There is no limit to the number of prior chemotherapy regimens received.
• Patients should be off radiation therapy, chemotherapy, investigational agents, hormonal therapy, or immunotherapy for 4 weeks (or 5 half-lives of the therapy, whichever is longer) prior to first dose in the study, and off Bevacizumab 6 weeks.
• Age greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status \<2 (Karnofsky \>70%)
• Patients must have normal organ and marrow function as defined below:
• leukocytes \>3,000/mcL
• absolute neutrophil count \>1,500/mcL without growth-factor support during the past month
• platelets \>100,000/mcL at all times during the screening period without platelet transfusion within 3 weeks
• total bilirubin \<2 X institutional upper limit of normal
• Hemoglobin (Hb) greater than or equal to 9 g/dL without transfusion for 3 weeks
• International normalized ratio (INR) \< 2.0
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase (SGPT) \<3 X institutional upper limit of normal, or \<5 ULN for patients with liver metastasis
• Creatinine within normal institutional limits

You may not qualify if:

• Patients who are receiving any other investigational agents.
• History of prior Janus kinase (JAK) or signal transducer and activator transcription 3 (STAT)3 inhibitor treatment.
• Patients with known brain metastases or spinal cord compression should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Patients must not have other invasive malignancies within the past 3 years (with the exception of adequately treated basal or squamous cell skin cancers, carcinoma in situ of the cervix and ductal carcinoma in situ (DCIS) of breast).
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD9150.
• Incompletely healed surgical incision prior to enrolment
• Any of the following cardiac criteria:
• Mean resting corrected Q wave and T wave (QT) interval (QTcF) \> 480 msec obtained from 3 electrocardiograms (ECGs)
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., complete left bundle branch block, third degree heart block
• Patients with uncontrolled hypertension (systolic blood pressure (SBP)\> 155, diastolic blood pressure (DBP)\> 90), unstable coronary disease (unstable angina, evidence of congestive heart failure (CHF), or myocardial infarction (MI) within 6 months of study)
• New York Heart Association (NYHA) greater than or equal to Grade II or greater.
• History of myocardial infarction within 6months prior to screening.
• 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.
• Pregnant and/or breastfeeding
• Human immunodeficiency virus (HIV)-positive patients or with history of hepatitis or with current chronic or active hepatitis. A past history of Hepatitis A is allowed.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Ascites; Gastrointestinal Neoplasms

Interventions

danvatirsen

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Results Point of Contact

• Title: Dr. Tim Greten
• Organization: National Cancer Institute

gretentf@nih.gov

301-451-4723

Study Officials

• Tim F Greten, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: National Cancer Institute

Study Record Dates

• First Submitted: April 15, 2015
• First Posted: April 16, 2015
• Study Start: April 3, 2015
• Primary Completion: April 7, 2016
• Study Completion: April 7, 2016
• Last Updated: May 15, 2017
• Results First Posted: May 15, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)