A Phase 1 Study Evaluating CB-5083 in Patients With Advanced Solid Tumors
Advanced Solid Tumors
Study Type
Study Phase
Phase 1
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: CB-5083
Type: Drug
Overall Status
This is a multicenter, open-label, phase 1 study of orally administered CB-5083 in adult patients with advanced solid tumors who have progressed or are non-responsive to available therapies and for which no standard therapy exists. The study will be conducted in 2 parts: an initial Dose Escalation Phase (phase 1a) of CB-5083 in patients with advanced solid tumors, followed by a dose expansion phase (phase 1b) which will include 2 parallel arms: one in patients with advanced pNETs and the second one in patients with advanced solid tumors carrying K RAS mutations.
Detailed Description
The objectives of the Dose Escalation Phase are to determine the safety, tolerability, PK and pharmacodynamic profiles as well as the MTD and RP2D of orally administered CB-5083. The objectives of the dose expansion phase are to confirm the safety and tolerability of the RP2D, to further assess the PK and pharmacodynamic profiles and to evaluate the preliminary anti-tumor activity of CB-5083 in patients with tumors for which there is biologic plausibility of unique sensitivity to CB-5083 mechanism of action (MOA) based on pre-clinical data.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

For both Escalation and Expansion arms:

1. Males and females ≥18 years of age;

2. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤1

3. Acceptable bone marrow and organ function at screening

4. Left ventricular ejection fraction informed (LVEF) ≥ 55%;

5. Ability to swallow and retain oral medications;

6. Negative serum beta-human Chorionic Gonadotropin (β-hCG) test in women of childbearing potential (WOCBP); and

7. Willing and able to provide written informed consent and comply with the requirements of the study.

8. Dose Escalation arm, only - Histologically confirmed advanced solid tumor for which standard therapy does not exist or is no longer effective

9. Dose Expansion arm, pNET Cohort only - Histologically confirmed low-grade or intermediate-grade, unresectable or metastatic pNET tumor with radiological documentation of disease progression < 12 months prior to enrollment for which standard therapy does not exist or is no longer effective. Functional and non-functional tumors can be included;

10. Dose Expansion arm, K-RAS Cohort only - Histologically confirmed malignancy with a K-RAS mutation that is metastatic or unresectable and for which standard therapy does not exist or is no longer effective.

Exclusion Criteria:

Both arms

1. Any prior treatment (with the exception of somatostatin analogues, which are allowed before and during the study in pNET patients at the investigator discretion in pNET patients) such as chemotherapy, immunomodulatory drug therapy, anti-neoplastic hormonal therapy (unless dose has been stable for 3 months prior to Baseline and will remain stable during the study), immunosuppressive therapy, or corticosteroids (unless administered to prevent contrast material reactions during radiographic procedures) received within the past 28 days or 5 half-lives, whichever is shorter.

2. Presence of an acute or chronic toxicity resulting from prior chemotherapy, with the exception of alopecia, that has not resolved to ≤ grade 1;

3. Received radiotherapy within the last 21 days (limited palliative radiation is allowed if ≥ 14 days prior);

4. Patient with primary brain tumors or known central nervous system (CNS) metastases;

5. Major surgery < 28 days from the start of treatment (major surgery is defined as a procedure requiring general anesthesia);

6. Minor surgery <14 days from the start of treatment (insertion of a vascular access device is not considered major or minor surgery);

7. Active infection requiring systemic therapy;

8. Known to be human immunodeficiency virus (HIV) positive or have an acquired immunodeficiency syndrome-related illness;

9. Uncontrolled congestive heart failure, angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug;

10. History of or ongoing cardiac dysrhythmias requiring treatment, atrial fibrillation of any grade, or persistent prolongation of the QTc;

11. History of esophageal bleeding due to varices;

12. Gastrointestinal disease that may interfere with the absorption of orally-administered drugs;

13. History of inflammatory bowel disease or other illness resulting in chronic diarrhea;

14. Known achlorhydria or history of gastrointestinal surgery that could reduce the acidity of the stomach;

15. Acute pancreatitis or cholecystitis within 6 months prior to Baseline;

16. Cirrhosis with severe liver dysfunction;

17. Previous malignancy, except for basal-cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the uterine cervix. Patients with other malignancies are eligible if they have remained disease free for at least 2 years prior to study entry;

18. Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with the interpretation of the study results and, in the Investigator's opinion, would make the patient inappropriate for entry into this study;

19. Use of any investigational agents within 28 days or 5 half-lives (whichever is shorter) prior to Baseline;

20. Concomitant treatment with pharmaceutical or herbal agents, which are potent inhibitors or inducers of cytochrome P450 (CYP) enzymes 2C9, 2C19, and 3A4 or are primarily metabolized by CYP 2C8 and 2C9. In addition, concomitant treatment with agents known to be substrates of the breast cancer resistance protein (BCRP) efflux pump is also excluded;

21. Concomitant use of drugs with a risk of causing prolonged QTc and/or Torsades de Pointes or a history of risk factors for Torsades de Pointes;

22. Concomitant use of any medication that alters stomach pH;

23. Pregnant or lactating female; and

24. Women of childbearing potential, or men who partner with a woman of childbearing potential, unless they agree to use dual barrier contraceptive methods which, in the Investigator's opinion, are effective and adequate for that patient's circumstances while on study drug and for 3 months afterward.
Scottsdale Healthcare Hospitals
Scottsdale, Arizona, United States
Status: Recruiting
Contact: Karen Lewandowski - 480-323-1072 - klewandowski@shc.org
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
Los Angeles, California, United States
Status: Recruiting
Contact: Bethany Wendel, RN - 310-967-4339 - Bethany.Wendel@cshs.org
University of Colorado
Aurora, Colorado, United States
Status: Recruiting
Contact: Sara Weisbart, RN - 720-848-0523 - SARA.WEISBART@UCDENVER.EDU
Emory University
Atlanta, Georgia, United States
Status: Recruiting
Contact: Meredith Renfroe - 404-778-1802 - marenfr@emory.edu
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, United States
Status: Recruiting
Contact: Maryann Redlinger, RN - 215-662-7758 - Maryann.Redlinger@uphs.upenn.edu
Start Date
October 2014
Cleave Biosciences, Inc.
Cleave Biosciences, Inc.
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page