Clinical trial NCT00620295: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2008-02-21
Enrollment: 17
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximum tolerated dose of bortezomib and gemcitabine
timeFrame: Day 21 (Week 3 - Cycle 1)
Secondary outcomes:
measure: Toxicity
timeFrame: 30 Days after Last Treatment
measure: Disease response as measured by RECIST criteria
timeFrame: Week 4
measure: Characterization of gemcitabine and metabolite pharmacokinetics (as part of co-enrollment in Population Pharmacokinetics and Pharmacogenetics of Gemcitabine in Adult Patients with Solid Tumors")
timeFrame: Pre-Dose
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Arkadiusz Dudek, MD
role: PRINCIPAL_INVESTIGATOR
References: