Bortezomib and Pemetrexed Disodium in Treating Patients With Advanced Non-Small Cell Lung Cancer or Other Solid Tumors

NCT00389805 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: UCDCC#158200412739H3E-US-X038
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Bortezomib and pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with pemetrexed disodium may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of two different schedules of bortezomib when given together with pemetrexed disodium and to see how well they work in treating patients with advanced non-small cell lung cancer or other solid tumors.

Conditions

Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Keywords

recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (4)

• Number of Patients Experiencing a Dose-limiting Toxicity (Phase I)

  Grade 4 thrombocytopenia or grade 3 thrombocytopenia associated with bleeding, requirement for transfusion or lasting \>7 days; febrile neutropenia; grade 3 neutropenia associated with infection; any other grade \>/=3 non-hematologic toxicity considered by the investigator to be related to study drug.

  Up to 36 months

• Number of Participants Who Experience Adverse Events (Phase I)

  Number of participants with treatment-related adverse events as assessed by CTCAE v3.0 (Phase I).

  Throughout the entire study (up to 36 months).

• Number of Patients With Grade ≥ 3 Toxicity (Phase I)

  Grade 3/4 toxicity occurring in a patient within 1 cycle.

  First cycle of treatment (3 weeks)

• Number of Patients Who Responded to Study Treatment (Phase II)

  To determine the response rate of bortezomib in combination with pemetrexed in patients with advanced NSCLC. Response rate was assessed by CT scan. CT scans was performed at baseline and every two cycles (prior to 3rd and 5th cycle). The evaluation of response was based on standard RECIST criteria.

  From start of treatment until disease progression/recurrence.

Secondary Outcomes (7)

• Number of Patients With Toxicity by NCI CTC v3.0 (Phase I)

  Up to 36 months

• Maximum Tolerated Dose of Bortezomib in Combination With Pemetrexel (Phase I)

  Up to 36 months

• Number of Participants With Response to Therapy as Measured by RECIST (Phase I)

  Up to 36 months

• Number of Participants With Toxicities (Phase II)

  Up to 36 months

• Analysis of Molecular Determinants in Tumor Samples (Phase II)

  Up to 36 months

Interventions

bortezomib DRUG

pemetrexed disodium DRUG

gene expression analysis GENETIC

mutation analysis GENETIC

protein expression analysis GENETIC

reverse transcriptase-polymerase chain reaction GENETIC

flow cytometry OTHER

immunoenzyme technique OTHER

immunohistochemistry staining method OTHER

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Cytologically or histologically confirmed diagnosis of 1 of the following: * Advanced solid tumor that progressed after standard therapy or for which no effective curative therapy exists (phase I) * Stage IIIB (pleural effusion) or IV non-small cell lung cancer (NSCLC) (phase II) * Disease must have progressed or recurred after 1 platinum-based therapy regimen * NSCLC that has progressed or recurred after first-line therapy for stage IIIA or IIIB disease allowed * Measurable disease * Disease in previously irradiated sites is considered measurable if there is clear disease progression following radiotherapy * Evaluable disease (bone metastases, pleural fluid, ascites) allowed (phase I) * No symptomatic brain metastasis or disease requiring steroids and anticonvulsants * Asymptomatic, previously treated (surgical resection or radiotherapy) brain metastases allowed provided patient is neurologically stable and has been off steroids and anticonvulsants for ≥ 4 weeks PATIENT CHARACTERISTICS: * Zubrod performance status 0-2 (phase I) or 0-1 (phase II) * Life expectancy ≥ 3 months * Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min * Bilirubin normal * AST ≤ 2.5 times upper limit of normal * Granulocyte count ≥ 1,500/mm³ * Platelet count of ≥ 100,000/mm³ * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after completion of study treatment * No pre-existing neuropathy ≥ grade 2 * No other prior malignancy except for the following (phase II): * Adequately treated basal cell or squamous cell skin cancer * In situ cervical cancer * Adequately treated stage I or II cancer currently in complete remission * Any other cancer from which the patient has been disease free for \> 5 years * No hypersensitivity to bortezomib, boron, or mannitol * No cardiovascular complications, including any of the following: * Myocardial infarction within the past 6 months * New York Heart Association class III-IV heart failure * Uncontrolled angina * Severe uncontrolled ventricular arrhythmias * Electrocardiographic (ECG) evidence of acute ischemia or active conduction system abnormalities * Any ECG abnormality at screening must be documented as not medically relevant PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior bortezomib or pemetrexed disodium * Any number of prior chemotherapy regimens allowed (phase I) * More than 4 weeks since prior chemotherapy (6 weeks for mitomycin C) and recovered * More than 2 weeks since prior radiotherapy and recovered * No nonsteroidal anti-inflammatory drugs (NSAIDs) or salicylates 2 days prior and 2 days after (5 days pre and post for long-acting NSAIDs) administration of pemetrexed disodium * No concurrent anticonvulsants that are metabolized by the cytochrome P450 pathway

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of California, Davis: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

University of California Davis Cancer Center

Sacramento, California, 95817, United States

Location

Related Publications (1)

• Davies AM, Ho C, Metzger AS, Beckett LA, Christensen S, Tanaka M, Lara PN, Lau DH, Gandara DR. Phase I study of two different schedules of bortezomib and pemetrexed in advanced solid tumors with emphasis on non-small cell lung cancer. J Thorac Oncol. 2007 Dec;2(12):1112-6. doi: 10.1097/JTO.0b013e31815ba7d0.

  PMID: 18090584 RESULT

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Bortezomib; Pemetrexed; Gene Expression Profiling; Reverse Transcriptase Polymerase Chain Reaction; Flow Cytometry; Immunoenzyme Techniques; Immunohistochemistry

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Genetic Techniques; Investigative Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Immunoassay; Immunologic Techniques; Molecular Probe Techniques; Histocytochemistry; Histological Techniques

Results Point of Contact

• Title: Analyst
• Organization: University of California, Davis

nlogihara@ucdavis.edu

916-734-8053

Study Officials

• Angela Davies, MD

  University of California, Davis

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

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: October 18, 2006
• First Posted: October 19, 2006
• Study Start: March 1, 2005
• Primary Completion: December 1, 2006
• Study Completion: June 1, 2007
• Last Updated: October 31, 2018
• Results First Posted: June 23, 2017

Record last verified: 2017-09

Locations

US (1)