- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00411593
Phase I-II for Patients With Recurrent or Refractory Non-small Cell Lung Cancer (NSCLC)
Phase I-II Study of Avastin®+ Bortezomib for Patients With Recurrent or Refractory Non-Squamous NSCLC
Primary Objective
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.
Secondary Objectives
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
Study Overview
Detailed Description
Bortezomib is designed to enter cells and interfere with a substance found inside cells that is responsible for allowing cells to divide.
Avastin® is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.
If you are found to be eligible to take part in this study, depending on when you enroll, you will be assigned to one of up to 4 treatment groups. There will be 3 participants in each of the first few groups, and an additional 30 participants in the last group. The first few (2 or 3) groups are part of the first phase of the study, and the last group (3rd or 4th) is part of the second phase. All participants will receive the same dose level of Avastin®. The amount of bortezomib you receive will depend on when you enroll in the study. The exact dose of bortezomib that you receive will be based on your height and weight. In the first phase of the study, groups of participants will be assigned to one of 2 bortezomib dose levels. The first group will receive the highest dose. The next groups will receive either that same dose level, or if intolerable side effects occurred, a lower dose level. For the second part of the study, the last group will receive the highest dose level that did not cause intolerable side effects in the other groups.
A cycle of treatment is 3 weeks (21 days). Bortezomib will be given once a week for the first 2 weeks of each cycle. Avastin® will be given every 3 weeks. (On Day 1 of each cycle, you will receive both bortezomib and Avastin®.)
Bortezomib will be injected through a needle in your vein. Each injection will last about 3-5 seconds. After receiving each dose of bortezomib, the clinic staff will check how well you are tolerating the drug. During that time, you will be asked about any side effects you may be experiencing. Your doctor may decrease or pause the dose of bortezomib if you experience certain side effects.
Avastin® will be given as an infusion through a needle in your vein, over 90 minutes. If you tolerate the 90-minute infusion well, the second infusion will be given over 60 minutes. If you tolerate the 60-minute infusion well, all following infusions will be given over 30 minutes. If you do not tolerate the shorter infusion time, future infusion times will be increased until a tolerable level is reached.
Every 3 weeks, you will have a physical exam, including measurement of vital signs and weight. Blood (about 2 teaspoons) will be drawn for routine tests. You will have a performance status evaluation. On Day 8 of each cycle of treatment, blood (about 2 teaspoons) will be drawn for routine tests. The level of protein in your urine will be monitored at least every 6 weeks.
You may continue receiving study treatment for as long as the cancer responds to the treatment or for up to 1 year. Your doctor may decide to take you off this study if you experience intolerable side effects or your health gets worse.
After you have stopped taking the study treatment, you will have a physical exam, including measurement of vital signs. Blood (about 2 teaspoons) will be drawn for routine tests. You will have a performance status evaluation, chest x-ray, and a CT or MRI scan. On an indefinite basis, the study nurse will contact you by telephone from time to time to see how you are doing.
This is an investigational study. Bortezomib has been FDA approved and it is registered in Europe for the treatment of multiple myeloma patients who have received at least one prior therapy. Avastin® has been FDA approved for the treatment of metastatic colorectal cancer and non-small cell lung cancer. However, bortezomib and Avastin® are not FDA-approved for this type of cancer, and they have been authorized for use together in research only. Up to 42 patients will take part in this study. All will be enrolled at M. D. Anderson.
Study Type
Phase
- Phase 2
- Phase 1
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
Other Names:
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD)
Time Frame: 21 days
|
MTD is defined as the highest dose level in which 6 patients have been treated with 2 patients with dose limiting toxicity (DLT).
|
21 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival
Time Frame: 1 year
|
Patients' progression free survival, 1 year survival and overall survival will be assessed.
The survival rate for time to event outcome will be estimated by Kaplan-Meier method.
All patients will be followed until death.
|
1 year
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Lung Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Bevacizumab
- Bortezomib
Other Study ID Numbers
- 2006-0045
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Lung Cancer
-
M.D. Anderson Cancer CenterRecruitingStage III Lung Cancer AJCC v8 | Lung Carcinoma | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Stage I Lung Cancer AJCC v8 | Stage IA1 Lung Cancer AJCC v8 | Stage IA2 Lung Cancer AJCC v8 | Stage... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage III Lung Cancer AJCC v8 | Stage IV Lung Cancer AJCC v8 | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Stage I Lung Cancer... and other conditionsUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI)RecruitingStage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Stage I Lung Cancer AJCC v8 | Stage IA1 Lung Cancer AJCC v8 | Stage IA2 Lung Cancer AJCC v8 | Stage IA3 Lung Cancer AJCC v8 | Stage IB Lung Cancer...United States
-
Dana-Farber Cancer InstituteMedWaves, IncNot yet recruitingLung Cancer | Lung Cancer Stage I | Lung Cancer Stage II | Stage I Lung Cancer | Stage I - II Primary Lung Cancer | Stage II Lung CancerUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingCaregiver | Stage III Lung Cancer AJCC v7 | Stage I Lung Cancer AJCC v7 | Stage II Lung Cancer AJCC v7 | Stage IB Lung Cancer AJCC v7 | Stage IA Lung Cancer AJCC v7 | Stage IIA Lung Cancer AJCC v7 | Stage IIB Lung Cancer AJCC v7 | Stage IIIA Lung Cancer AJCC v7 | Stage IIIB Lung Cancer AJCC v7United States
-
WindMIL TherapeuticsBristol-Myers SquibbTerminatedNSCLC | Lung Cancer | Lung Cancer Metastatic | Lung Cancer, Non-small Cell | Non Small Cell Lung Cancer | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non Small Cell Lung Cancer MetastaticUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI); Genentech, Inc.RecruitingStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Lung Non-Small Cell Carcinoma | Stage III Lung Cancer AJCC v8 | Stage IV Lung Cancer AJCC v8 | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung... and other conditionsUnited States
-
Emory UniversityNational Cancer Institute (NCI)TerminatedLung Non-Small Cell Carcinoma | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage I Lung Cancer AJCC v8 | Stage IA1 Lung Cancer AJCC v8 | Stage IA2 Lung Cancer AJCC v8 | Stage IA3 Lung Cancer AJCC v8 | Stage IB Lung Cancer...United States
-
University of California, San FranciscoMerck Sharp & Dohme LLCWithdrawnLung Non-Small Cell Carcinoma | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage I Lung Cancer AJCC v8 | Stage IA1 Lung Cancer AJCC v8 | Stage IA2 Lung Cancer AJCC v8 | Stage IA3 Lung Cancer AJCC v8 | Stage IB Lung Cancer...United States
-
City of Hope Medical CenterNational Cancer Institute (NCI)CompletedStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage III Lung Cancer AJCC v8 | Metastatic Lung Carcinoma | Stage IV Lung Cancer AJCC v8 | Head and Neck Carcinoma | Lung Carcinoma | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung... and other conditionsUnited States
Clinical Trials on Bevacizumab
-
National Cancer Institute (NCI)Active, not recruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian Clear Cell Cystadenocarcinoma | Ovarian Endometrioid Adenocarcinoma | Ovarian Serous Cystadenocarcinoma | Endometrial Clear Cell Adenocarcinoma | Endometrial Serous Adenocarcinoma | Recurrent... and other conditionsUnited States
-
National Cancer Institute (NCI)NRG OncologyCompletedGlioblastoma | Gliosarcoma | Recurrent Glioblastoma | Oligodendroglioma | Giant Cell Glioblastoma | Recurrent Brain NeoplasmUnited States, Canada
-
M.D. Anderson Cancer CenterRecruitingStage IB Hepatocellular Carcinoma AJCC v8 | Stage II Hepatocellular Carcinoma AJCC v8 | Resectable Hepatocellular Carcinoma | Stage I Hepatocellular Carcinoma AJCC v8 | Stage IA Hepatocellular Carcinoma AJCC v8United States
-
National Cancer Institute (NCI)Active, not recruitingOvarian Endometrioid Adenocarcinoma | Primary Peritoneal High Grade Serous Adenocarcinoma | Fallopian Tube Endometrioid Adenocarcinoma | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Ovarian High Grade Serous Adenocarcinoma | Platinum-Resistant... and other conditionsUnited States, Canada
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI)RecruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian Endometrioid Adenocarcinoma | Ovarian Clear Cell Adenocarcinoma | Fallopian Tube Adenocarcinoma | Fallopian Tube Serous Adenocarcinoma | Ovarian Serous Adenocarcinoma | Fallopian Tube... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma, Not Otherwise Specified | Stage IVA Cervical Cancer AJCC v6 and v7 | Recurrent Cervical Carcinoma | Stage IV Cervical Cancer AJCC v6 and v7 | Stage IVB Cervical Cancer AJCC v6 and v7United States
-
Northwestern UniversityNational Cancer Institute (NCI); Ipsen BiopharmaceuticalsCompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Platinum-Resistant Ovarian Carcinoma | Refractory Ovarian Carcinoma | Refractory Fallopian Tube... and other conditionsUnited States
-
National Cancer Institute (NCI)Active, not recruitingStage IV Cutaneous Melanoma AJCC v6 and v7 | Stage IIIC Cutaneous Melanoma AJCC v7 | Unresectable MelanomaUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); Merck Sharp & Dohme LLC; Celldex TherapeuticsRecruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Recurrent Endometrial Serous Adenocarcinoma | Ovarian Clear Cell Adenocarcinoma | Recurrent Platinum-Resistant Ovarian Carcinoma | Platinum-Sensitive Ovarian Carcinoma | Recurrent Fallopian... and other conditionsUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingMetastatic Lung Non-Small Cell Carcinoma | Stage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage III Lung Cancer AJCC v8 | Stage IV Lung Cancer AJCC v8 | Stage IIIA Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Stage IIIC Lung Cancer AJCC v8 | Locally Advanced Lung Non-Small... and other conditionsUnited States