Phase I-II for Patients With Recurrent or Refractory Non-small Cell Lung Cancer (NSCLC)

NCT00411593 | Withdrawn Phase 1

• 1 other identifier: 2006-0045
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Lung Cancer

Keywords

Non-Small Cell Lung Cancer; Lung Cancer; NSCLC; Bortezomib; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  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 Outcomes (1)

• Progression Free Survival

  1 year

Study Arms (1)

Avastin® + Bortezomib

EXPERIMENTAL

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.

Drug: Bevacizumab; Drug: Bortezomib

Interventions

Bevacizumab DRUG

15 g/kg by vein every 3 weeks on day 1 of each cycle.

Also known as: Avastin, Anti-VEGF Monoclonal Antibody, rhuMAb-VEGF

Avastin® + Bortezomib

Bortezomib DRUG

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.

Also known as: Velcade, LDP-341, MLN341, PS-341

Avastin® + Bortezomib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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.

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• Genentech, Inc.: collaborator

Related Links

• UT MD Anderson Cancer Center website

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Bevacizumab; Bortezomib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Bonnie S. Glisson, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2006
• First Posted: December 14, 2006
• Study Start: November 1, 2006
• Primary Completion: May 1, 2007
• Study Completion: May 1, 2007
• Last Updated: February 8, 2012

Record last verified: 2012-02