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Bortezomib and Gemcitabine in Treating Older Patients With Advanced Solid Tumors
This study is ongoing, but not recruiting participants.
First Received: February 20, 2008   Last Updated: February 6, 2009   History of Changes
Sponsor: Masonic Cancer Center, University of Minnesota
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00620295
  Purpose

RATIONALE: Bortezomib may stop the growth of solid tumors by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with gemcitabine may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib and gemcitabine in treating older patients with advanced solid tumors.


Condition Intervention Phase
Breast Cancer
Colorectal Cancer
Head and Neck Cancer
Kidney Cancer
Lung Cancer
Ovarian Cancer
Pancreatic Cancer
Prostate Cancer
Sarcoma
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: bortezomib
Drug: gemcitabine hydrochloride
Other: pharmacological study
Phase I

Study Type: Interventional
Study Design: Treatment
Official Title: Phase I Study of Bortezomib and Gemcitabine in Elderly Patients With Solid Tumors (X05227)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose of bortezomib and gemcitabine [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity as measured by NCI-CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Disease response as measured by RECIST criteria [ Designated as safety issue: No ]
  • Characterization of gemcitabine and metabolite pharmacokinetics (as part of co-enrollment in Population Pharmacokinetics and Pharmacogenetics of Gemcitabine in Adult Patients with Solid Tumors") [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: March 2007
Estimated Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To determine the maximum tolerated dose of weekly bortezomib and gemcitabine in treating elderly patients with advanced solid tumors.

Secondary

  • To characterize the quantitative and qualitative toxicities of bortezomib and gemcitabine in these patients.
  • To obtain preliminary information about the anti-tumor activity of bortezomib and gemcitabine.
  • To characterize gemcitabine and metabolite pharmacokinetics in patients receiving concurrent bortezomib therapy.

OUTLINE: This is a phase I dose escalation study of bortezomib and gemcitabine.

Patients receive gemcitabine IV over 30 minutes followed 1 hour later by bortezomib IV over 3-5 seconds on days 1 and 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gemcitabine and bortezomib until the maximum tolerated dose of the combination is determined.

Blood is collected periodically for pharmacokinetic and pharmacogenetic studies.

After completion of study treatment, patients are followed every 3 months for up to 1 year.

  Eligibility

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed diagnosis of advanced non-hematologic malignancy, including any of the following:

    • Breast cancer
    • Lung cancer
    • Colon cancer
    • Pancreatic cancer
    • Head and neck cancer
    • Sarcoma
  • Must have failed or become intolerant to prior standard therapy and is no longer likely to respond to such therapy (for all diseases except pancreatic cancer)

    • Pancreatic cancer patients may be enrolled with no prior therapy requirements since gemcitabine is the current standard of care 1st line therapy
  • Measurable or nonmeasurable disease
  • Concurrent enrollment in the University of Minnesota study "Population Pharmacokinetics and Pharmacogenetics of Gemcitabine in Adult Patients with Solid Tumors" (Human Subjects Code 0508M72989) required
  • No symptomatic brain metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status of 0-1
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10 g/dL
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 3.0 times ULN (5 times ULN if liver has tumor involvement)
  • AST and ALT ≤ 3.0 times ULN (5 times ULN if liver has tumor involvement)
  • Calculated or measured creatinine clearance > 30 mL/minute
  • Fertile patients must use effective contraception during and for 3 months after study participation
  • No serious concomitant medical or psychiatric disorders (e.g., active infection or uncontrolled diabetes) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study
  • No myocardial infarction within the past 6 months
  • No NYHA Class III or IV heart failure
  • No uncontrolled angina
  • No severe uncontrolled ventricular arrhythmias
  • No electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • No peripheral neuropathy ≥ grade 2
  • No known hypersensitivity to bortezomib, boron or mannitol

PRIOR CONCURRENT THERAPY:

  • Recovered from all prior therapy
  • Prior systemic chemotherapy, immunotherapy, or biological therapy allowed
  • At least 3 months since prior bortezomib and/or gemcitabine
  • At least 2 weeks since prior systemic therapy
  • At least 3 weeks since prior investigational agents (for reasons other than the treatment of cancer)
  • At least 2 weeks since prior radiotherapy
  • No prior radiotherapy to ≥ 25% of the bone marrow
  • No prior radiotherapy to the whole pelvis
  • No concurrent filgrastim (G-CSF) or other hematologic support during course 1 of study treatment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00620295

Locations
United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Arkadiusz Dudek, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000586510, UMN-2006LS040, UMN-X05227
Study First Received: February 20, 2008
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00620295     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent pancreatic cancer
stage II pancreatic cancer
stage III pancreatic cancer
stage IV pancreatic cancer
recurrent breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
male breast cancer
extensive stage small cell lung cancer
recurrent small cell lung cancer
recurrent non-small cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent colon cancer
stage III colon cancer
stage IV colon cancer
recurrent prostate cancer
stage III prostate cancer
stage IV prostate cancer
recurrent squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the larynx
stage III squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
recurrent verrucous carcinoma of the larynx
stage III verrucous carcinoma of the larynx

Additional relevant MeSH terms:
Thoracic Neoplasms
Anti-Infective Agents
Antimetabolites, Antineoplastic
Neuroectodermal Tumors, Primitive
Molecular Mechanisms of Pharmacological Action
Prostatic Diseases
Pancreatic Neoplasms
Physiological Effects of Drugs
Colonic Diseases
Urogenital Neoplasms
Urologic Neoplasms
Ileal Diseases
Rectal Diseases
Duodenal Neoplasms
Neoplasms, Connective and Soft Tissue
Neoplasms by Site
Lung Neoplasms
Therapeutic Uses
Kidney Diseases
Gemcitabine
Breast Diseases
Endocrine Gland Neoplasms
Digestive System Neoplasms
Genital Neoplasms, Female
Breast Neoplasms
Endocrine System Diseases
Genital Diseases, Male
Protease Inhibitors
Carcinoma
Neuroectodermal Tumors

ClinicalTrials.gov processed this record on November 09, 2009