Phase I-II for Patients With Recurrent or Refractory Non-small Cell Lung Cancer (NSCLC)
This study has been withdrawn prior to enrollment.
(Lack of Patient Accrual)
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
First received: December 12, 2006
Last updated: February 7, 2012
Last verified: February 2012
The primary objective of this phase I-II study is to evaluate:
- Phase I: Assess the maximum tolerated dose (MTD) of bortezomib in a weekly schedule with bevacizumab given every 3 weeks.
- Phase II: Using the MTD established in phase I, assess efficacy of the combination as indicated by progression-free survival.
The secondary objectives of this study are to evaluate:
- Response rates and duration of response
- 1 year survival
- Overall survival
- Qualitative and quantitative toxicity
- Circulating endothelial cells (CECs) prior to treatment, prior to cycle 2, and/or at the time of progression
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Phase I-II Study of Avastin®+ Bortezomib for Patients With Recurrent or Refractory Non-Squamous NSCLC
Primary Outcome Measures:
Secondary Outcome Measures:
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||May 2007 (Final data collection date for primary outcome measure)
Experimental: Avastin® + Bortezomib
Phase I - 3 * 3 design, enrolling patients to receive Avastin® at a fixed dose of 15 mg/kg every 3 weeks and Bortezomib dosed at 1.6 mg/m2 weekly for 2 weeks out of 3.
Phase II - The MTD for Bortezomib from the weekly schedule that is chosen will be combined with Avastin® to estimate the rate of progression-free survival.
15 g/kg by vein every 3 weeks on day 1 of each cycle.
- Anti-VEGF Monoclonal Antibody
Phase I Starting dose: 1.6 mg/m2 by vein on days 1, 8 of each 3 week cycle.
Phase II: MTD from Phase I.
|Ages Eligible for Study:
||18 Years and older (Adult, Senior)
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Female subject is either post-menopausal (Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential) or surgically sterilized or willing to use an acceptable method of birth control (i.e. a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study.
- All patients must have an Eastern Cooperative Oncology Group (ECOG)Performance Status of 0 - 2
- Patients must have histologically or cytologically proven selected Stage IIIB (T4 lesion due to malignant pleural or pericardial effusion) or Stage IV advanced non-small cell lung cancer or recurrent disease after previous surgery and/or radiation.
- No history of or active brain metastases
- Patients must have measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI). Measurable disease must be assessed within 28 days prior to registration. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease.
- Recurrent or progressive cancer can be within a previously radiated site
- Patients must have received one or two prior systemic therapies, one of which contained a platinum compound. No prior Bortezomib or antiangiogenic agent is permitted. Prior radiation is permitted; however, at least two weeks must have elapsed since the completion of prior radiation therapy and patients must have recovered from all associated toxicities at the time of registration. At least two weeks must have elapsed since surgery (thoracic or other major surgeries) and patients must have recovered from all associated toxicities at the time of registration.
- Patients must have a serum creatinine </= the institutional upper limit of normal (i.e. 1.5 mg/dL) AND a creatinine clearance >/= 40 cc/min determined by either urine collection and testing or calculation using the following formula: Calculated Creatinine Clearance = (140 - age) * Weight(kg) * (0.85 if female)/ 72 * creatinine (mg/dL)
- Patients must have an Absolute neutrophil count (ANC)>/= 2,000/µl and platelet count >/= 100,000/µl obtained within 28 days prior to registration. Hemoglobin: >9.0 * 10^9/L
- Patients must have adequate hepatic function documented by a serum bilirubin </= institutional upper limit of normal (1.0) and liver enzymes (serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT)) </= 3.0 * the institutional upper limit of normal obtained within 28 days prior to registration
- Peripheral neuropathy, if present, must be < Grade 2 (NCI Common Terminology Criteria for Adverse Events Version 3.0).
- Patients known to be HIV-positive and taking HAART therapy are not eligible due to possible pharmacokinetic interactions
- Patients must not be planning to receive any other concomitant anticancer treatment including chemotherapy, radiation therapy, biologic agents or any other investigational drugs
- Patient must be >/= 18 years of age.
- Patients must be informed of the investigation nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
- Patients meeting any of the following exclusion criteria are not to be enrolled in the study. Participation in an experimental drug study within 4 weeks of the first treatment on this trial: Blood pressure > 140/90 mm Hg, History of stroke within 6 months, Clinically significant peripheral vascular disease, Evidence of bleeding diathesis or coagulopathy, Presence of central nervous system or brain metastases
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study.
- Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0
- Urine protein: creatinine ratio >/= 1.0 at screening
- Serious non-healing wound, ulcer, or bone fracture
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class II or heart failure, unstable angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, and ECG abnormality at Screening has to be documented by the investigator as not medically relevant
- Patients with squamous histology
- Patients with hematemesis or more than ½ teaspoon of hemoptysis within 6 months of study entry.
- Patients requiring full dose oral or parenteral anticoagulation.
- Abdominal fistula, GI perforation, or abdominal abscess within the last 6 months
- Patient has hypersensitivity to boron or mannitol
- Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. Patient has received other investigational drugs within 28 days before enrollment
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study
- No other prior or concurrent malignancy is allowed except for: non-melanoma skin cancers, in situ cervical cancer, and any cancer from which the patient has been disease-free for 3 years or more.
- Pregnant or nursing women may not participate in this trial because of the increased risk of fetal harm including fetal death from the chemotherapeutic agents. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
- Patients requiring treatment with Nonsteroidal anti-inflammatory drugs (NSAIDS), antiplatelet agents, or aspirin > 325 mg/day
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00411593
M.D. Anderson Cancer Center
Millennium Pharmaceuticals, Inc.
||Bonnie S. Glisson, MD
||M.D. Anderson Cancer Center
||M.D. Anderson Cancer Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||December 12, 2006
||February 7, 2012
||United States: Food and Drug Administration
Keywords provided by M.D. Anderson Cancer Center:
Non-Small Cell Lung Cancer
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on August 24, 2016
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Angiogenesis Modulating Agents
Physiological Effects of Drugs