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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00389805
First received: October 18, 2006
Last updated: February 6, 2009
Last verified: July 2007
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: bortezomib
Drug: pemetrexed disodium
Genetic: gene expression analysis
Genetic: mutation analysis
Genetic: protein expression analysis
Genetic: reverse transcriptase-polymerase chain reaction
Other: flow cytometry
Other: immunoenzyme technique
Other: immunohistochemistry staining method
Phase 1
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Two Different Schedules of Bortezomib (VELCADE, PS-341) and Pemetrexed (ALIMTA) in Advanced Solid Tumors, With Emphasis on Non-Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate (Phase II) [ Designated as safety issue: No ]
  • Safety (Phase I) [ Designated as safety issue: Yes ]
  • Dose-limiting toxicity (Phase I) [ Designated as safety issue: Yes ]
  • Feasibility (Phase I) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity by NCI CTC v3.0 (Phase I) [ Designated as safety issue: Yes ]
  • Maximum tolerated dose (Phase I) [ Designated as safety issue: Yes ]
  • Treatment efficacy (Phase I) [ Designated as safety issue: No ]
  • Frequency and severity of toxicities (Phase II) [ Designated as safety issue: Yes ]
  • Molecular determinants (Phase II) [ Designated as safety issue: No ]
  • Importance of folate-associated gene expression and response or outcome (Phase II) [ Designated as safety issue: No ]
  • Effect of bortezomib on patients that over express NF-kB, BCL-2, and BCL-xL (Phase II) [ Designated as safety issue: No ]
  • Prognosis associated with lost p27 expression (Phase II) [ Designated as safety issue: No ]
  • Effects of bortezomib on down-regulating HIF-1 in reducing levels PAI-1, vascular endothelial growth factor, and/or osteopontin (Phase II) [ Designated as safety issue: No ]
  • Shed tumor DNA in plasma as a biomarker (Phase II) [ Designated as safety issue: No ]
  • Biological activity of bortezomib (Phase II) [ Designated as safety issue: No ]

Estimated Enrollment: 86
Study Start Date: March 2005
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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, including any of the following:

    • Enzyme-inducing drugs

      • Primidone
      • Carbamazepine
      • Phenobarbital
      • Phenytoin
    • Enzyme-inhibiting drugs

      • Oxcarbazepine
      • Topiramate
      • Zonisamide
      • Valproic acid
  Contacts and Locations
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: NCT00389805

Locations
United States, California
University of California Davis Cancer Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
Investigators
Study Chair: Angela Davies, MD University of California, Davis
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00389805     History of Changes
Other Study ID Numbers: CDR0000505966, UCDCC-158, UCDCC-200412739-2
Study First Received: October 18, 2006
Last Updated: February 6, 2009
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Bortezomib
Pemetrexed
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014