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About
This phase I trial studies the side effects and the best dose of cilengitide when given together with paclitaxel weekly in treating patients with solid tumors that have spread nearby or to other areas of the body and cannot be removed by surgery. Cilengitide may stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel, work in different ways to the stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cilengitide together with paclitaxel may kill more tumor cells.
Full description
PRIMARY OBJECTIVES:
I. To determine the maximally tolerated dose (MTD) of cilengitide and paclitaxel at weekly dose schedule. (Cohort I) II. To describe the toxicities associated with cilengitide and paclitaxel. III. To describe any antitumor activity of cilengitide and paclitaxel at weekly dose schedule.
IV. To characterize pharmacokinetics (PK) of cilengitide and paclitaxel with the proposed schedule and correlate PK parameters to clinical outcome. (Cohort I) V. To examine the effect of cilengitide and paclitaxel on circulating cysteine-rich, angiogenic inducer, 61 (Cyr61) using a novel "sandwich enzyme-linked immunosorbent assay (ELISA)" and to correlate this effect with clinical response. (Cohort II) VI. To evaluate the information obtained through use of items from the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Phase I studies.
VII. To determine if tumor tissue expression of alpha v beta 3 (αvβ3) and CYR61 correlate with therapeutic response to cilengitide with paclitaxel. (Cohort II)
OUTLINE: This is a dose-escalation study of cilengitide.
Patients receive cilengitide intravenously (IV) over 1 hour on days* 1, 8, and 15 and paclitaxel IV over 1 hour on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
NOTE: *Some patients receive cilengitide IV over 1 hour on days 1, 2, 8, 9, 15, and 16.
After completion of study treatment, patients are followed up for 3 months.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Histologic proof of cancer that is now unresectable (solid tumors, excluding lymphoma)
For Cohort II only:
Absolute neutrophil count (ANC) >= 1500/μL
Hemoglobin (Hgb) >= 9 g/dL
Platelets (PLT) >= 100,000/μL
Total bilirubin =< 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) =< 3 x ULN or AST =< 5 x ULN if liver involvement
Creatinine =< 1.5 x ULN
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, or 1 (or Karnofsky performance status [KPS] > 70)
Ability to provide informed consent
Willingness to return to the enrolling Mayo Clinic institution for follow-up
Life expectancy >= 12 weeks
All patients: Willingness to provide blood samples for the mandatory correlative research component
For Cohort II, tissue biopsies are mandatory
Women of childbearing potential only: negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential including women within 2 years of post-menopause
Exclusion criteria
Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
Uncontrolled 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
Any of the following prior therapies:
Chemotherapy =< 21 days prior to registration
Mitomycin C/nitrosoureas =< 42 days prior to registration
Immunotherapy =< 14 days prior to registration
Biologic therapy =< 14 days prior to registration
Prior investigational therapy =< 28 days prior to registration
Full field radiation therapy =< 28 days prior to registration or limited field radiation therapy < 14 days prior to registration
Major surgery (i.e., laparotomy) =< 4 weeks prior to registration; minor surgery =< 2 weeks prior to registration; Note: insertion of a vascular access device is not considered major or minor surgery in this regard
Unresolved toxicities from prior therapy with the exception of alopecia that have not resolved to =< grade 1, unless the patient has a chronic, stable =< grade 2 toxicity that would not interfere with the evaluation of the study agents
New York Heart Association classification III or IV
Central nervous system (CNS) metastases or seizure disorder; Note: CNS metastases are allowed if previously treated and stable for at least 4 weeks
Any of the following:
Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive on highly active antiretroviral therapy (HAART) therapy
Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
Other active malignancy =< 3 years prior to registration; EXCEPTIONS: nonmelanotic skin cancer or carcinoma-in-situ of the cervix; Note: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
Uncontrolled hypertension, labile hypertension of history of poor compliance with antihypertensive medication
Patients with active, bleeding diathesis
Non-disease related- major surgery, =< 28 days or minor surgery =< 7 days prior to registration
Primary purpose
Allocation
Interventional model
Masking
13 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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