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Bortezomib and Gemcitabine in Treating Older Patients With Advanced Solid Tumors

Primary Purpose

Breast Cancer, Colorectal Cancer, Head and Neck Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
bortezomib
gemcitabine hydrochloride
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring recurrent pancreatic cancer, recurrent breast cancer, recurrent small cell lung cancer, recurrent non-small cell lung cancer, recurrent colon cancer, recurrent prostate cancer, recurrent head and neck cancer, ovarian cancer, recurrent uterine cancer, recurrent kidney cancer, recurrent osteosarcoma

Eligibility Criteria

70 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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
  • 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)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (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
  • 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

Exclusion Criteria:

  • Symptomatic brain metastases
  • 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
  • Myocardial infarction within the past 6 months
  • New York Heart Association (NYHA) Class III or IV heart failure
  • Uncontrolled angina
  • Severe uncontrolled ventricular arrhythmias
  • Electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Peripheral neuropathy ≥ grade 2
  • Known hypersensitivity to bortezomib, boron or mannitol
  • Prior radiotherapy to ≥ 25% of the bone marrow
  • Prior radiotherapy to the whole pelvis
  • Concurrent filgrastim (G-CSF) or other hematologic support during course 1 of study treatment

Sites / Locations

  • Masonic Cancer Center at University of Minnesota

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Gemcitabine / Bortezomib

Arm Description

Gemcitabine will be administered as a 30 minute intravenous infusion at the patient's assigned dose on day 1 and day 8 of a 21 day cycle. Bortezomib will be given 1 hour after gemcitabine by IVP over 3 to 5 seconds followed by a standard saline on days 1 and 8 of a 21 day treatment cycle until disease progression or for a maximum of 6 cycles.

Outcomes

Primary Outcome Measures

Maximum tolerated dose of bortezomib and gemcitabine
A minimum of a 3 week period (1 cycle) must be completed by all patients within a dose level before dose escalation to the next level may occur. A cycle is defined as treatment day 1 and 8 with follow-up through day 21.

Secondary Outcome Measures

Toxicity
Toxicity will be graded using the NCI's Common Terminology Criteria for Adverse Events (CTCAE 3.0)
Disease response as measured by RECIST criteria
The best overall response is the best response recorded from the start of treatment until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since the treatment began.
Characterization of gemcitabine and metabolite pharmacokinetics (as part of co-enrollment in Population Pharmacokinetics and Pharmacogenetics of Gemcitabine in Adult Patients with Solid Tumors")
Pharmacokinetics will be done in conjunction with the dosing day 1 of cycle 1 whenever possible.

Full Information

First Posted
February 20, 2008
Last Updated
November 27, 2017
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT00620295
Brief Title
Bortezomib and Gemcitabine in Treating Older Patients With Advanced Solid Tumors
Official Title
Phase I Study of Bortezomib and Gemcitabine in Elderly Patients With Solid Tumors (X05227)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
October 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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 intravenously (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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Colorectal Cancer, Head and Neck Cancer, Kidney Cancer, Lung Cancer, Ovarian Cancer, Pancreatic Cancer, Prostate Cancer, Sarcoma
Keywords
recurrent pancreatic cancer, recurrent breast cancer, recurrent small cell lung cancer, recurrent non-small cell lung cancer, recurrent colon cancer, recurrent prostate cancer, recurrent head and neck cancer, ovarian cancer, recurrent uterine cancer, recurrent kidney cancer, recurrent osteosarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gemcitabine / Bortezomib
Arm Type
Experimental
Arm Description
Gemcitabine will be administered as a 30 minute intravenous infusion at the patient's assigned dose on day 1 and day 8 of a 21 day cycle. Bortezomib will be given 1 hour after gemcitabine by IVP over 3 to 5 seconds followed by a standard saline on days 1 and 8 of a 21 day treatment cycle until disease progression or for a maximum of 6 cycles.
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
Bortezomib will be given 1 hour after gemcitabine by intravenous pyelogram (IVP) over 3 to 5 seconds followed by a standard saline flush or through a running intravenous (IV) line at the patient's assigned dose (1.0 up to 1.8 mg/m^2) on days 1 and 8 of a 21 day treatment cycle until disease progression or for a maximum of 6 cycles.
Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Other Intervention Name(s)
Gemzar
Intervention Description
Gemcitabine will be administered as a 30 minute intravenous infusion at the patient's assigned dose (800 up to 1000 mg/m^2) on day 1 and day 8 of a 21 day cycle.
Primary Outcome Measure Information:
Title
Maximum tolerated dose of bortezomib and gemcitabine
Description
A minimum of a 3 week period (1 cycle) must be completed by all patients within a dose level before dose escalation to the next level may occur. A cycle is defined as treatment day 1 and 8 with follow-up through day 21.
Time Frame
Day 21 (Week 3 - Cycle 1)
Secondary Outcome Measure Information:
Title
Toxicity
Description
Toxicity will be graded using the NCI's Common Terminology Criteria for Adverse Events (CTCAE 3.0)
Time Frame
30 Days after Last Treatment
Title
Disease response as measured by RECIST criteria
Description
The best overall response is the best response recorded from the start of treatment until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since the treatment began.
Time Frame
Week 4
Title
Characterization of gemcitabine and metabolite pharmacokinetics (as part of co-enrollment in Population Pharmacokinetics and Pharmacogenetics of Gemcitabine in Adult Patients with Solid Tumors")
Description
Pharmacokinetics will be done in conjunction with the dosing day 1 of cycle 1 whenever possible.
Time Frame
Pre-Dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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) Aspartate aminotransferase (AST) and alanine aminotransferase (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 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 Exclusion Criteria: Symptomatic brain metastases 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 Myocardial infarction within the past 6 months New York Heart Association (NYHA) Class III or IV heart failure Uncontrolled angina Severe uncontrolled ventricular arrhythmias Electrocardiographic evidence of acute ischemia or active conduction system abnormalities Peripheral neuropathy ≥ grade 2 Known hypersensitivity to bortezomib, boron or mannitol Prior radiotherapy to ≥ 25% of the bone marrow Prior radiotherapy to the whole pelvis Concurrent filgrastim (G-CSF) or other hematologic support during course 1 of study treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arkadiusz Dudek, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center at University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

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Bortezomib and Gemcitabine in Treating Older Patients With Advanced Solid Tumors

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