Phase I/II Study to Evaluate the Efficacy and Safety of a Combination Chemotherapy

NCT00424840 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: UM200601
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

A pilot trial of combination of bortezomib, bevacizumab and carboplatin as first line therapy in patients with metastatic Non-Small Cell Lung Cancer (NSCLC). Phase I and II study of this combination in first line setting will be conducted in order to properly estimate the efficacy and safety of this regimen. This will form the basis for future studies comparing this combination to what is now considered standard regimen for first line therapy in patients with NSCLC, carboplatin, paclitaxel and bevacizumab.

Conditions

Lung Cancer

Keywords

lung cancer, Carboplatin, bortezomib, Bevacizumab

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Who Require Dose Delay/Reduction in Dose of Bortezomibin the First Cycle

  Dose limiting toxicity at Level 1,2 and 3: Number of subjects who required dose delay/reduction in dose of bortezomib in the first cycle of treatment. DLT defined by any of the following during first cycle: (1) GR4 neutropenia or thrombocytopenia, (2) Greater than GR3 non-hematological toxicity except alopecia or inadequately treated nausea or vomiting or (3) neurosensory toxicity of GR2 with pain or any neurotoxicity greater than GR2.

  up to 21 days for each dosing cycle

Study Arms (3)

Bortezomib 1.3 mg/m2

EXPERIMENTAL

Level 1 of Bortezomib Dose Escalation in combination with Carboplatin AUC6, Bevacizumab 15 mg/kg and Taxotere 70 + G-CSF

Drug: Bortezomib 1.3 mg/m2; Drug: Carboplatin AUC 6; Drug: Bevacizumab; Drug: Taxotere

Bortezomib 1.6 mg/m2

EXPERIMENTAL

Level 2 of Bortezomib Dose Escalation in combination with Carboplatin AUC6, Bevacizumab 15 mg/kg and Taxotere 70 + G-CSF

Drug: Bortezomib 1.6 mg/m2; Drug: Carboplatin AUC 6; Drug: Bevacizumab; Drug: Taxotere

Bortezomib 1.8 mg/m2

EXPERIMENTAL

Level 3 of Bortezomib Dose Escalation in combination with Carboplatin AUC6, Bevacizumab 15 mg/kg and Taxotere 70 + G-CSF

Drug: Bortezomib 1.8 mg/m2; Drug: Carboplatin AUC 6; Drug: Bevacizumab; Drug: Taxotere

Interventions

Bortezomib 1.3 mg/m2 DRUG

Level I (every 21 day cycle, D8), 1.3 mg/m2: Day 1: bevacizumab 15 mg/kg ,carboplatin Area Under the Curve (AUC 6) 900mg, bortezomib 1.3 mg/m2 Day 8 : bortezomib 1.3 mg/m2 Level II (every 21 day cycle): Day 1: bevacizumab 15 mg/kg, carboplatin Area Under the Curve (AUC 6) 900mg, bortezomib 1.6 mg/m2 Day 8 : bortezomib 1.6 mg/m2 Level III(every 21 day cycle): Day 1: bevacizumab 15 mg/kg, carboplatin Area Under the Curve (AUC 6) 900mg, bortezomib 1.8 mg/m2 Day 8 : bortezomib 1.8 mg/m2

Also known as: Velcade

Bortezomib 1.3 mg/m2

Bortezomib 1.6 mg/m2 DRUG

Level II (every 21 day cycle, D8), 1.6 mg/m2

Also known as: Velcade

Bortezomib 1.6 mg/m2

Bortezomib 1.8 mg/m2 DRUG

Level III (every 21 day cycle, D8) 1.8 mg/m2

Also known as: Velcade

Bortezomib 1.8 mg/m2

Carboplatin AUC 6 DRUG

Carboplatin AUC6

Also known as: Carboplatin

Bortezomib 1.3 mg/m2; Bortezomib 1.6 mg/m2; Bortezomib 1.8 mg/m2

Bevacizumab DRUG

Bevacizumab 15 mg/kg

Bortezomib 1.3 mg/m2; Bortezomib 1.6 mg/m2; Bortezomib 1.8 mg/m2

Taxotere DRUG

Taxotere 70 + G-CSF

Bortezomib 1.3 mg/m2; Bortezomib 1.6 mg/m2; Bortezomib 1.8 mg/m2

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed SCLC (adeno- and large cell, anaplastic carcinoma and broncho-alveolar-carcinoma). Patients with squamous-cell histology are eligible with extra thoracic or peripheral lung lesions only.
• Sputum cytology alone not acceptable evidence of cell type. Cytologic specimens obtained by brushing, washings, or needle aspiration of defined lesions will be acceptable. Mixed tumors will be categorized by the predominant cell type unless a small cell anaplastic elements are present, in which case the patient is ineligible.
• Stage III B because of pleural effusion or Stage IV disease
• Measurable disease.
• Age: 18 years or older
• No history of thrombotic, hemorrhagic, or coagulopathy disorders
• international normalized ratio (INR\<1.5) and a prothrombin time (PTT) no greater than normal limits of normal within 1 week prior to registration. NB: subjects with lung cancer placed on anticoagulant therapy for a thrombotic event are not eligible for this study.
• No gross hemoptysis (defined as bright red blood of ½ teaspoon or more)
• No central nervous system (CNS) or brain metastasis
• Laboratory Criteria (completed \<2 weeks before enrollment):
• Hematologic: white blood cell (WBC) \> 3500/mm3 or absolute neutrophil count (ANC) \> 1500/mm3 and platelet count \> 100 000/ mm3;
• Hepatic: Total bilirubin \< 1.5 mg/dl
• Renal: Creatinine \< 1.5 mg/dl. or calculated

You may not qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status \< 2
• Be free of active infection.
• Be available for active follow up.
• No prior chemotherapy for metastatic disease.
• Be disease free for \> 5 years if they had a prior second malignancy other than treated basal cell carcinoma or squamous cell skin cancer, or carcinoma in situ of the cervix.
• Female subject post-menopausal; surgically sterilized or willing to use an acceptable method of birth control for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study.
• CNS or brain metastasis
• Patient has = or greater Grade 2 peripheral neuropathy within 14 days before enrollment.
• Known previous sensitivity reactions with boron, or mannitol,
• Patients with known HIV positivity
• Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• Blood pressure of \>150/100 mmHG
• History of myocardial infarction or stroke within 6 months
• Clinically significant peripheral vascular disease
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study.

Sponsors & Collaborators

• University of Massachusetts, Worcester: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

University of Massachusetts Medical School

Worcester, Massachusetts, 01655-0002, United States

Location

Related Publications (2)

• Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9.

  PMID: 2702835 BACKGROUND

• Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50. doi: 10.1056/NEJMoa061884.

  PMID: 17167137 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Bortezomib; Carboplatin; Bevacizumab; Docetaxel

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Limitations and Caveats

The study was closed prematurely because of poor accrual prior to initiation of Phase 2, and is underpowered to definitely estimated the response rate and progression free survival.

Results Point of Contact

• Title: Dr. William Walsh
• Organization: University of Massachusetts Medical School

William.Walsh@umassmemorial.org

508-334-5539

Study Officials

• William Walsh, MD

  University of MassachusettsMedical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Principle Investigator

Study Record Dates

• First Submitted: January 18, 2007
• First Posted: January 22, 2007
• Study Start: June 1, 2006
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: February 1, 2019
• Results First Posted: February 1, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)