A Dose Escalation Study of OMP-52M51 in Subjects With Solid Tumors
This study is currently recruiting participants.
Verified March 2013 by OncoMed Pharmaceuticals, Inc.
Information provided by (Responsible Party):
OncoMed Pharmaceuticals, Inc.
First received: January 24, 2013
Last updated: March 19, 2013
Last verified: March 2013
This is an open-label Phase 1a dose escalation study of single-agent OMP-52M51 in subjects with relapsed or refractory solid tumors. Study includes a dose escalation phase and expansion phase. Subjects will be assessed for safety, immunogenicity, pharmacokinetics, biomarkers, and efficacy.
Relapsed or Refractory Solid Tumors
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase 1 Dose Escalation Study of OMP-52M51 in Subjects With Solid Tumors
Primary Outcome Measures:
- Safety profile of OMP-52M51 in subjects with relapsed or refractory solid tumors [ Time Frame: Subjects will be assessed for DLTs from Days 0-29. Adverse events will be reported through 30 days after the last dose ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||May 2014 (Final data collection date for primary outcome measure)
|Ages Eligible for Study:
||18 Years to 90 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
Subjects must meet all of the following criteria to be eligible for the study:
- Age >18 years
- ECOG performance status <2 (see Appendix B)
- Solid tumor malignancy for which there is no remaining standard therapy or either refuse or are not considered to be candidates for any remaining standard therapy.
- Must have a tumor that is measurable or evaluable per RECIST v1.1 in the dose escalation phase. In the expansion cohort(s), subjects must have measurable disease.
- Subjects must have Formalin-Fixed, Paraffin-Embedded (FFPE) tissue available either archived or fresh core or punch needle biopsied at study entry (two fresh cores/punches preferred whenever possible) for determination of Notch1 pathway activation status.
- Must have received their last chemotherapy, biologic, radiotherapy, or investigational therapy at least 4 weeks prior to enrollment; 6 weeks if the last regimen included BCNU or mitomycin C.
Subjects must have normal organ and marrow function as defined below:
- Absolute neutrophil count >1500/mL without growth factor support in the past 7 days
- Platelets >100,000/mL without transfusions in the past 7 days
- Total bilirubin <1.5 X institutional upper limit of normal (ULN) (<2X ULN for subjects with Gilbert's syndrome)
- AST (SGOT) and ALT (SGPT) <3 X institutional ULN (for subjects with hepatic involvement <5 X institutional ULN but cannot be associated with elevated bilirubin)
- PT/INR and aPTT within 1.5 X institutional ULN
- Creatinine <1.5 X institutional ULN OR
- Creatinine clearance >60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal
- Normal Ejection Fraction (>50%) on ECHO scan or MUGA
- 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, she should inform the Investigator immediately.
- Ability to understand and the willingness to sign a written informed consent document
Subjects who meet any of the following criteria will not be eligible for participation in the study:
- Currently receiving any therapeutic treatment for their malignancy including other investigational agents
- Prior treatment with gamma secretase inhibitors or other Notch 1 inhibitors
- Uncontrolled seizure disorder, active neurologic disease, or active CNS involvement except for individuals who have previously-treated CNS metastases, are asymptomatic, and have no requirement for higher doses of corticosteroids (> prednisone 10mg orally per day) or anti-seizure medication for at least 4 weeks prior to first dose of study drug.
- History of a Grade 4 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, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women or nursing women
- Ongoing malignancies or malignancies in remission <3 years other than the malignancies included in this trial. Patients with history of known squamous cell skin cancers within the past 3 years will not be included in this trial. The following prior malignancies are allowable irrespective of when they occurred: in situ carcinoma of the cervix, in situ ductal breast cancer, and low-grade local bladder cancer.
- Subjects with known HIV infection
- Known bleeding disorder or coagulopathy
- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
- Hemoptysis in excess of 2.5 mL(or one-half teaspoon) within 8 weeks of first dose of study drug.
- Subjects receiving heparin, warfarin, or other similar anticoagulants, except for subjects on low molecular weight heparin for DVT/PE prophylaxis. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents.
- New York Heart Association Classification II, III, or IV (see Appendix D)
Subjects with poorly controlled blood pressure (defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) that is not responsive to medical therapy. Subjects taking antihypertensive medications must be taking ≤2 medications to obtain this level of blood pressure control.
NOTE: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry.
- Subjects with 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.
Subjects with known clinically significant gastrointestinal disease including, but not limited to:
- inflammatory bowel disease
- active peptic ulcer disease
- known intraluminal metastatic lesion(s) with risk of bleeding
- history of abdominal fistula, GI perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment
- Subjects with diarrhea at time of enrollment or have an ongoing requirement for anti diarrheal therapy
Please refer to this study by its ClinicalTrials.gov identifier: NCT01778439
|University of Colorado Denver -RCI-South Tower
|Aurora, Colorado, United States, 80045 |
|Contact: Gail Eckhardt, M.D. 303-724-3850 |
|Principal Investigator: Gail Eckhardt, M.D. |
|South Texas Accelerated Research Therapeutics, LLC
|San Antonio, Texas, United States, 78229 |
|Contact: Amita Patnaik, M.D. 210-593-5270 |
|Principal Investigator: Amita Patnaik, M.D. |
OncoMed Pharmaceuticals, Inc.
No publications provided
||OncoMed Pharmaceuticals, Inc.
History of Changes
|Other Study ID Numbers:
|Study First Received:
||January 24, 2013
||March 19, 2013
||United States: Food and Drug Administration
Keywords provided by OncoMed Pharmaceuticals, Inc.:
relapsed or refractory
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on June 18, 2013