A Study of Gemcitabine and Demcizumab (OMP-21M18) With or Without Abraxane® as 1st-line Treatment in Subjects With Locally Advanced or Metastatic Pancreatic Cancer

• Status: Completed
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to test the safety and determine the optimal dose of a new experimental drug, demcizumab (OMP-21M18), when given in combination with gemcitabine with or without (+/-) Abraxane®. Historically, single agent gemcitabine has been the standard treatment for pancreatic cancer. However, recent data suggests that gemcitabine plus Abraxane® may be superior to gemcitabine alone, thus this combination is emerging as the new standard therapy for pancreatic cancer. However, Abraxane® has not been approved for the treatment of pancreatic cancer at this time. Demcizumab is a humanized monoclonal antibody and was developed to target cancer stem cells. This study is sponsored by OncoMed Pharmaceuticals, which is referred to as OncoMed or the Sponsor in this consent form. The study is designed to test the safety of demcizumab at different dose levels when given with gemcitabine +/- Abraxane® and the effects, both good and bad, that it has on participants. Demcizumab may block the growth of cancer stem cells, the remaining tumor cells, and it may also prevent the growth of new blood vessels that tumors need to grow and spread. Although demcizumab has been administered with gemcitabine to cancer patients, it has not been given in combination with gemcitabine and Abraxane®; thus, it is not known if it will provide any benefit to participants and may cause harmful side effects.

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

Details

• Lead Sponsor: OncoMed Pharmaceuticals, Inc.
• Collaborator: Novotech (Australia) Pty Limited
• Treatments: Albumin-Bound Paclitaxel; Gemcitabine; Paclitaxel

Criteria

Inclusion criteria

1. Subjects must have histologically or cytologically confirmed locally advanced or metastatic pancreatic cancer. In addition, subjects must have a tumor that is at least 1 cm in a single dimension and is radiographically apparent on Computed Topography (CT) or Magnetic Resonance Imaging (MRI). Prior chemotherapy or radiotherapy is not allowed.

2. Age >21 years

3. Eastern Cooperative Oncology Group (ECOG) performance status <2 (see Appendix B)

4. Life expectancy of more than 3 months

5. Subjects must have normal organ and marrow function as defined below:

• Leukocytes >3.5 x 109/L

• Absolute neutrophil count >1.25 x 109/L

• Hemoglobin >100 g/L

• Platelets >125 X 109/L

• Total bilirubin <2 X institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) <5 X institutional ULN

• Alkaline phosphatase <5 X institutional ULN

• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) within institutional ULN

• Creatinine <1.5 X institutional ULN OR

• Calculated creatinine clearance >60 mL/min using the Cockcroft and Gault formula as follows:

Creatinine clearance (mL/min) = (140 - age) x ideal body weight [kg] 0.814 x serum creatinine [µmol/L] For women, multiply the value from the equation above by 0.85. Where age is in years, weight is in kg, and serum creatinine is in µmol/L

6. Women of childbearing potential must have had a prior hysterectomy or have a negative serum pregnancy test and be using adequate contraception prior to study entry and must agree to use adequate contraception from study entry through at least 6 months after discontinuation of study drug. Men must also agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and from study entry through at least 6 months after discontinuation of study drug. Should a woman enrolled in the study or a female partner of a man enrolled in the study become pregnant or suspect she is pregnant while participating in this study or within 6 months after discontinuation of study drug, the Investigator should be informed immediately.

7. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Subjects who meet any of the following criteria will not be eligible for participation in the study:

1. Subjects receiving any other investigational agents or anti-cancer therapy.

2. Subjects with brain metastases (subjects must have a CT scan or MRI of the head within 28 days prior to enrollment to rule out brain metastases), uncontrolled seizure disorder, or active neurologic disease

3. History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy

4. Significant intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

5. Pregnant women or nursing women

6. Subjects with known HIV infection

7. Known bleeding disorder or coagulopathy

8. Subjects receiving heparin, warfarin, or other similar anticoagulants. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents.

9. Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease

10. New York Heart Association Classification II, III, or IV

11. Subjects with a blood pressure (BP) of >140/90 mmHg. Subjects taking antihypertensive medications must be taking ≤2 medications to obtain this level of BP control.

12. Subjects with tumors that are currently involving the lumen of the gastrointestinal tract

13. Subjects with current evidence of cardiac ischemia or heart failure within the last 6 months, subjects who are receiving any medications for cardiac ischemia, subjects with a B-type natriuretic peptide (BNP) value of >100 pg/mL, subjects with a LVEF of <50%, subjects with pulmonary hypertension defined as a peak tricuspid velocity >3.4 m/s on doppler echocardiogram or subjects that have received a total cumulative dose of ≥400 mg/m2 doxorubicin

14. Subjects with electrocardiogram (ECG) evidence of ischemia or ≥ Grade 2 ventricular arrhythmia, subjects who have a history of acute myocardial infarction within 6 months, or subjects with unstable angina