AZD9150, a STAT3 Antisense Oligonucleotide, in People With Malignant Ascites
Condition: Ovarian Cancer; Ovarian Neoplasms; Ascites; Gastrointestinal Cancer; Gastrointestinal Neoplasms
MeSH terms: Neoplasms; Ovarian Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Ascites
Intervention: AZD9150
Intervention description: 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: PARACENTESIS; STAT3 Antisense Oligonucleotide; Ascites; AZD9150; Surgical Resection

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.
    

Eligibility criteria:

        -INCLUSION CRITERIA:

          1. Patients must have histologically or cytologically confirmed gastrointestinal (G)I
             malignancies or ovarian cancer prior to entering this study.

          2. 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.

          3. 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.

          4. 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.

          5. Age greater than or equal to 18 years.

          6. Eastern Cooperative Oncology Group (ECOG) performance status <2 (Karnofsky >70%)

          7. 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

             OR

          8. Patients must have recovered from any acute toxicity related to prior therapy,
             including surgery. Toxicity should be < grade 1

          9. Ejection fraction > 50% on echocardiogram.

         10. The effects of AZD9150 on the developing human fetus are unknown. For this reason
             women of child-bearing potential should use reliable methods of contraception from the
             time of screening until 6 months after discontinuing study treatment. Acceptable
             methods of contraception include tubal ligation, tricycle combined oral or transdermal
             contraceptives, copper-banded intra-uterine devices and vasectomized partner. It is
             not known whether AZD9150 has the capacity to induce hepatic enzymes so hormonal
             contraceptives should be combined with a barrier method of contraception. Should a
             woman become pregnant or suspect she is pregnant while she or her partner is
             participating in this study, she should inform her treating physician immediately.
             Women of child-bearing potential must have a negative pregnancy test prior to entry.
             Male patients should use reliable methods of contraception such as barrier
             contraception i.e. condoms during sexual activities with women of child-bearing
             potential and refrain from sperm donation during the trial and for a washout period of
             at least 6 months. If male patients wish to father children they should be advised to
             arrange for freezing of sperm samples prior to the start of study treatment.

         11. Ability of subject to understand and the willingness to sign a written informed
             consent document.

        EXCLUSION CRITERIA:

          1. Patients who are receiving any other investigational agents.

          2. History of prior Janus kinase (JAK) or signal transducer and activator transcription 3
             (STAT)3 inhibitor treatment.

          3. 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.

          4. 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).

          5. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to AZD9150.

          6. Incompletely healed surgical incision prior to enrolment

          7. Ongoing therapy with oral or parenteral anticoagulants (e.g., heparin, warfarin).
             Lowdose anticoagulants for maintenance of catheter patency are not exclusionary.

          8. 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

          9. 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)

         10. New York Heart Association (NYHA) greater than or equal to Grade II or greater.

         11. History of myocardial infarction within 6months prior to screening.

         12. 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.

         13. Pregnant and/or breastfeeding

         14. 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.

         15. History of recurrent bacterial infections unrelated to hepatocellular carcinoma (HCC)
             (particularly skin or lung)

         16. Bacterial peritonitis within 30 days

         17. History of, or presently active or chronic viral infections (i.e. zoster or hepatitis)

         18. History of known latent or active tuberculosis, signs of active or latent tuberculosis
             on chest X-ray, skin test showing an induration of >10 mm or more or according to
             local recommendations.

         19. Active bleeding disorders and high likelihood of bleeding or conditions or medications
             known to increase the risk of bleeding. Patients with bleeding diathesis and subjects
             who are receiving anticoagulation treatment with INR > 2 are excluded.

         20. History of recurrent thrombosis or any thrombosis within the past 6 months

         21. Family history consistent with thrombophilia or hypofibrinolysis

         22. Patients who have received liver transplantation

         23. History of clinically significant liver abnormalities other than liver metastasis

         24. Presence of hepatic encephalopathy within 4 weeks of 1st dose

         25. Judgment by the investigator that the patient should not participate in the study if
             the patient is unlikely to comply with study procedures, restrictions and requirements