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

NCT01189929 | Completed Phase 1 DMC

• 1 other identifier: M18-002
• Study Type: interventional
• Target: 57
• Locations: 3 countries
• Sites: 6

Brief 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.

Conditions

Pancreatic Cancer

Keywords

Phase 1,; dose escalation,; histologically; cytologically; confirmed; malignancy; metastatic

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated dose of demcizumab (OMP-21M18) when combined with gemcitabine +/- Abraxane®

  Until disease progression

Secondary Outcomes (5)

• To determine the safety of gemcitabine +/- Abraxane® plus demcizumab (OMP-21M18)

  Until disease progression

• To determine the rate of immunogenicity of gemcitabine +/- Abraxane® plus demcizumab (OMP-21M18)

  Until disease progression

• To determine the preliminary efficacy of gemcitabine +/- Abraxane® plus demcizumab (OMP-21M18)

  Until disease progression

• To determine population pharmacokinetics of demcizumab (OMP-21M18)

  Until disease progression

• To determine the exploratory biomarker changes of gemcitabine plus demcizumab (OMP-21M18)

  Until disease progression

Study Arms (1)

Gemcitabine and demcizumab With or Without Abraxane®

EXPERIMENTAL

Gemcitabine and demcizumab With or Without Abraxane®

Drug: Demcizumab; Drug: Abraxane®; Drug: Gemcitabine

Interventions

Demcizumab DRUG

Up to 50 subjects will be enrolled at up to 8 centers in Australia, New Zealand, and Spain. Up to 28 days (4 weeks) prior to treatment you will undergo testing to determine your eligibility to take part in this study, and then if you are enrolled in the study you will receive intravenous (in the vein) infusions of the demcizumab administered once every 2 weeks, and gemcitabine and Abraxane® administered weekly for 3 weeks, out of every 4 weeks. After 9 weeks, you will undergo assessments to determine the status of your disease. If there is no evidence of progression of your disease or if your tumor is smaller, you will continue to receive one additional infusion of demcizumab, and you will continue to receive infusions of gemcitabine and Abraxane® once weekly for 3 consecutive weeks out of every 4 weeks until it has been shown that your cancer has progressed. You will undergo assessments every 8 weeks thereafter to determine the status of your disease.

Also known as: OMP-21M18

Gemcitabine and demcizumab With or Without Abraxane®

Abraxane® DRUG

Abraxane® which will be administered by IV infusion at a dose of 125 mg/m2 over 30 minutes once a week for 3 weeks in a row, followed by a week of rest.

Gemcitabine and demcizumab With or Without Abraxane®

Gemcitabine DRUG

Gemcitabine will be administered intravenously over 30 minutes initially at a dose of 1000 mg/m2 once a week for 3 weeks in a row, followed by a week of rest. If you develop side effects during this time period, your physician may decide to hold or reduce the dose of gemcitabine.

Gemcitabine and demcizumab With or Without Abraxane®

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age \>21 years
• Eastern Cooperative Oncology Group (ECOG) performance status \<2 (see Appendix B)
• Life expectancy of more than 3 months
• 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:

You may not qualify if:

• Subjects who meet any of the following criteria will not be eligible for participation in the study:
• Subjects receiving any other investigational agents or anti-cancer therapy.
• 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
• History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy
• 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
• Pregnant women or nursing women
• Subjects with known HIV infection
• Known bleeding disorder or coagulopathy
• Subjects receiving heparin, warfarin, or other similar anticoagulants. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents.
• Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease
• New York Heart Association Classification II, III, or IV
• 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.
• Subjects with tumors that are currently involving the lumen of the gastrointestinal tract
• 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
• 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

Sponsors & Collaborators

• OncoMed Pharmaceuticals, Inc.: lead
• Novotech (Australia) Pty Limited: collaborator

Study Sites (6)

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

The Austin Hospital

Heidelberg, Victoria, Australia

Location

Christchurch Hospital

Christchurch, New Zealand

Location

Waikato Hospital

Hamilton, New Zealand

Location

START Madrid

Madrid, Spain

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasms; Neoplasm Metastasis

Interventions

demcizumab; Albumin-Bound Paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2010
• First Posted: August 27, 2010
• Study Start: August 1, 2010
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: September 9, 2020

Record last verified: 2020-09

Locations

NZ (2); AU (3); ES (1)