Study of JI-101 in Patients With Advanced Low Grade Endocrine Tumors, Ovarian Cancers or K-RAS Mutant Colon Cancers

• Status: Terminated
• Trial end date: 2012-08-01
• Target enrollment: 0
• Participant gender: All

Summary

The study consists of two parts: Drug Interaction (Pharmacokinetic) Phase and Pharmacodynamic Phase

The primary study objective for the Drug Interaction Study is to determine the pharmacokinetic interactions between RAD001 and JI-101.

The primary study objective for the Pharmacodynamic Study is progression-free survival at 2 moths, evaluated separately in each of the three cohorts.

These will include a determination of tumor response using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria and an assessment of ephrinB4 expression in blood samples.

Secondary objectives are to determine safety and tolerability of JI-101. The investigational products are everolimus (42-O-(2-hydroxyethyl) rapamycin) and JI-101 (1-[1-(2-amino-pyridin-4-ylmethyl)-1H-indol-4-yl]-3-(5-bromo-2 methoxy-phenyl)-urea)

Eligible patients meeting all study entry criteria will be enrolled in the study. For the Drug Interaction study, patients with solid tumors will receive a single dose (10 mg) of Everolimus by mouth on Day 1 and Day 8 and JI-101 capsules (200 mg) by mouth on Day 8 and Day

15. For the Pharmacodynamic Study, all patients will receive JI-101 capsules by mouth (200 mg BID) for 28 day treatment cycles.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Utah
• Collaborator: Jubilant Innovation Ltd.
• Treatments: Everolimus; Sirolimus

Criteria

Inclusion Criteria:

1. Male or female, ≥18 years of age

2. For the Pharmacokinetic Drug Interaction Study: Histologically or cytologically confirmed advanced solid tumors that are refractory to all standard of care therapy or for whom no standard therapy is available, or for whom other standard therapies the patient has denied. For the Pharmacodynamic Study: Histologically or cytologically confirmed metastatic/advanced ovarian carcinoma or metastatic/advanced KRAS mutant colorectal cancer or metastatic/advanced Head and neck squamous cell cancer (HNSCC) that are refractory to all standard therapies therapy or for whom no standard therapy is available, or for whom other standard therapies the patient has denied.

3. At least one measurable tumor as defined by RECIST

4. Minimum of 4 weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy

5. Eastern Cooperative Oncology Group (ECOG) of 0 to 2

6. Organ &marrow function as defined in the protocol.

7. No evidence of preexisting uncontrolled hypertension as documented by two baseline blood pressure readings taken at least 1 hour apart

8. Clinically euthyroid

9. Normal range cardiac function

10. For female patients of child-bearing potential, a negative serum pregnancy test at Screening.

11. Current use of an acceptable form of double-barrier birth control

12. Have provided written informed consent

Exclusion Criteria:

1. Known brain or other central nervous system metastases metastases that are not stable for 3 months or longer

2. Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation.

3. Major surgery, radiotherapy, chemotherapy, or cytokine therapy within 28 days of Study Day 0;

4. History of intratumoral bleeding or evidence of bleeding diathesis or coagulopathy

5. Female patients who are pregnant, planning a pregnancy, or who are breastfeeding

6. Known allergy or hypersensitivity to JI-101 or everolimus or any component of the investigational products

7. Use of an investigational drug/device/biologic within 28 days of Study Day 0

8. Current drug or alcohol abuse or history of drug or alcohol abuse within the past two years

9. Known history of or serologic positivity for the Hepatitis B Virus (HBV), or the Hepatitis C Virus (HCV), or for the human immunodeficiency virus (HIV)

10. History of cardiac abnormalities

11. Gastrointestinal (GI) abnormalities

12. Use of concomitant medications that prolong the QT/QTc interval within 14 days prior to Study Day 0

13. History of cerebrovascular accident including transient ischemic attack within the past 6 months

14. History of pulmonary embolism or deep vein thrombosis within the past 6 months

15. History of significant retinopathy or any progressive eye disease that could lead to severe loss of visual acuity or visual field loss during the study period

16. Treatment with heparin or heparin analogs

17. Inability or unwillingness to meet the requirements of the study

18. Other current active malignancy or history of malignancy within the past five years, except for cervical carcinoma in situ, basal cell carcinoma that has been surgically removed, or prostate cancer that is being managed with watchful waiting.

19. Any clinically significant abnormal finding at screening that the investigator judges would interfere with study participation