A Study of Gemcitabine Plus OMP-21M18 as 1st-line Treatment in Subjects With Pancreatic Cancer
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Purpose
The purpose of this study is to test the safety and determine the optimal dose of a new experimental drug, OMP-21M18, when given in combination with gemcitabine, a drug that is a standard treatment for advanced pancreatic cancer that has not been treated previously with chemotherapy. OMP-21M18 is a humanized monoclonal antibody (a protein made in the laboratory) and was developed to target cancer stem cells. The way the body handles OMP-21M18 will also be investigated. Up to 40 participants, 21 years or older, will be enrolled at up to 6 centres in Australia, New Zealand and Spain. Following informed consent and screening, participants will receive intravenous infusions of OMP-21M18 every 28 days and Gemcitabine administered weekly for the first 7 weeks. After 9 weeks, participants will undergo assessments to determine their disease status. Participants will continue to receive infusions of OMP-21M18 every 28 days and gemcitabine once weekly for 7 weeks follow by a week rest from treatment until disease progression.
| Condition | Intervention | Phase |
|---|---|---|
|
Pancreatic Cancer |
Drug: OMP-21M18 |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase 1b Study of Gemcitabine Plus OMP-21M18 as 1st-line Treatment in Subjects With Locally Advanced or Metastatic Pancreatic Cancer |
- - To determine the maximum tolerated dose of OMP-21M18 when combined with gemcitabine [ Time Frame: Until disease progression ] [ Designated as safety issue: Yes ]
- To determine the safety of gemcitabine plus OMP-21M18 [ Time Frame: Until disease progression ] [ Designated as safety issue: Yes ]
- To determine the rate of immunogenicity of gemcitabine plus OMP-21M18 [ Time Frame: Until disease progression ] [ Designated as safety issue: No ]
- To determine the preliminary efficacy of gemcitabine plus OMP-21M18 [ Time Frame: Until disease progression ] [ Designated as safety issue: No ]
- To determine population pharmacokinetics [ Time Frame: Until disease progression ] [ Designated as safety issue: No ]
- To determine the exploratory biomarker changes of gemcitabine plus OMP-21M18 [ Time Frame: Until disease progression ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 40 |
| Study Start Date: | August 2010 |
| Estimated Study Completion Date: | January 2014 |
| Estimated Primary Completion Date: | May 2013 (Final data collection date for primary outcome measure) |
-
Drug: OMP-21M18
Current cancer therapies often produce an initial reduction in tumour size but may not have longterm benefits. One possible explanation for this is the presence cancer cell known as a cancer stem cells. Cancer stem cells represent a small part of the tumour but are believed to be responsible for much of the growth and spread of the cancer. They may also be more resistant to traditional therapy, such as chemotherapy and radiation therapy.
The purpose of this study is to test the safety and determine the optimal dose of a new experimental drug, OMP-21M18, when given in combination with gemcitabine, a drug that is a standard treatment for advanced pancreatic cancer that has not been treated previously with chemotherapy. OMP-21M18 is a humanized monoclonal antibody (a protein made in the laboratory) and was developed to target cancer stem cells. The way the body handles OMP-21M18 will also be investigated.
Up to 40 participants, 21 years or older, will be enrolled at up to 6 centres in Australia, New Zealand and Spain. Following informed consent and screening, participants will receive intravenous infusions of OMP-21M18 every 28 days and Gemcitabine administered weekly for the first 7 weeks. After 9 weeks, participants will undergo assessments to determine their disease status. Participants will continue to receive infusions of OMP-21M18 every 28 days and gemcitabine once weekly for 7 weeks follow by a week rest from treatment until disease progression. A Data Safety Monitoring Board (DSMB) will review the data for the 6 participants at each dose level after the last participant in that group has been treated for 56 days and decide whether it is safe to move up to the next highest dose level. After confirming the optimum dose, 14 additional participants will be treated at the highest dose level that the DSMB considers safe.
Participants will be assessed for disease status every 8 weeks and for safety at every visit and for 30 days after the end of study drug treatment. Safety will be assessed by adverse event monitoring, physical examination, vital signs, blood tests, cardiac monitoring, and participant interview. Response rates, duration of response, time to progression, and survival will be evaluated, requiring CT or MRI scans and CA199 (tumour marker) levels at baseline and then every 8 weeks. The development of antibodies to treatment will be assessed throughout the study and up to 12 weeks after the end of study drug treatment. Blood samples will be taken to assess whether OMP-21M18 is producing desired changes to the genes and proteins related to the cancer (biomarkers).
The study includes an optional part which will investigate how variations in people's genetic makeup affect their response to medications. This involves the collection of one blood sample just before participants receive their first dose of study treatment. DNA will be extracted from the blood sample for testing.
Eligibility| Ages Eligible for Study: | 21 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion criteria
- 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:
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
- 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.
- 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:
- 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
Contacts and Locations| Contact: Robert Stagg, PharmD | 650-995-8289 | robert.stagg@oncomed.com |
| Australia, New South Wales | |
| Royal Prince Alfred Hospital | Recruiting |
| Camperdown, New South Wales, Australia, 2050 | |
| Principal Investigator: Peter Grimison, MD | |
| Australia, Victoria | |
| Box Hill Hospital | Recruiting |
| Box Hill, Victoria, Australia, 3128 | |
| Principal Investigator: Prasad Cooray, MD | |
| The Austin Hospital | Recruiting |
| Heidelberg, Victoria, Australia | |
| Principal Investigator: Niall Tebbutt, MD | |
| New Zealand | |
| Christchurch Hospital | Recruiting |
| Christchurch, New Zealand | |
| Principal Investigator: Mark Jeffery, MD | |
| Waikato Hospital | Recruiting |
| Hamilton, New Zealand | |
| Principal Investigator: Michael Jameson, MD | |
| Spain | |
| START Madrid | Recruiting |
| Madrid, Spain | |
| Principal Investigator: Manuel Hidalgo, M.D., Ph.D. | |
More Information
No publications provided
| Responsible Party: | OncoMed Pharmaceuticals, Inc. |
| ClinicalTrials.gov Identifier: | NCT01189929 History of Changes |
| Other Study ID Numbers: | M18-002 |
| Study First Received: | August 25, 2010 |
| Last Updated: | December 14, 2011 |
| Health Authority: | Australia: Department of Health and Ageing Therapeutic Goods Administration New Zealand: Health and Disability Ethics Committees New Zealand: Medsafe |
Keywords provided by OncoMed Pharmaceuticals, Inc.:
|
Phase 1, dose escalation, histologically cytologically |
confirmed malignancy metastatic |
Additional relevant MeSH terms:
|
Pancreatic Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Gemcitabine Antimetabolites, Antineoplastic Antimetabolites |
Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Radiation-Sensitizing Agents |
ClinicalTrials.gov processed this record on May 23, 2013