Bortezomib and Gemcitabine in Treating Older Patients With Advanced Solid Tumors - Full Text View

Sponsor:	Masonic Cancer Center, University of Minnesota
Information provided by:	Masonic Cancer Center, University of Minnesota
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	Drug: bortezomib Drug: gemcitabine hydrochloride	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Study of Bortezomib and Gemcitabine in Elderly Patients With Solid Tumors (X05227)

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Colorectal Cancer Head and Neck Cancer Kidney Cancer Lung Cancer Ovarian Cancer Pancreatic Cancer Prostate Cancer Soft Tissue Sarcoma

Drug Information available for: Gemcitabine Gemcitabine hydrochloride Bortezomib

U.S. FDA Resources

Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:

Maximum tolerated dose of bortezomib and gemcitabine [ Time Frame: Day 21 (Week 3 - Cycle 1) ] [ Designated as safety issue: Yes ]
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 [ Time Frame: 30 Days after Last Treatment ] [ Designated as safety issue: Yes ]
Toxicity will be graded using the NCI's Common Terminology Criteria for Adverse Events (CTCAE 3.0)
Disease response as measured by RECIST criteria [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
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") [ Time Frame: Pre-Dose ] [ Designated as safety issue: No ]
Pharmacokinetics will be done in conjunction with the dosing day 1 of cycle 1 whenever possible.

Enrollment:	17
Study Start Date:	March 2007
Study Completion Date:	October 2009
Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Gemcitabine / Bortezomib 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.	Drug: bortezomib 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. Other Name: Velcade Drug: gemcitabine hydrochloride 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. Other Name: Gemzar

Arms

Assigned Interventions

Experimental: Gemcitabine / Bortezomib

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.

Drug: bortezomib

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.

Other Name: Velcade

Drug: gemcitabine hydrochloride

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.

Other Name: Gemzar

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

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

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

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:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Arkadiusz Dudek, M.D., Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:	NCT00620295 History of Changes
Other Study ID Numbers:	CDR0000586510, UMN-2006LS040, UMN-X05227, x464
Study First Received:	February 20, 2008
Last Updated:	April 13, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:

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

Additional relevant MeSH terms:

Breast Neoplasms
Carcinoma, Renal Cell
Kidney Neoplasms
Colorectal Neoplasms
Head and Neck Neoplasms
Lung Neoplasms
Ovarian Neoplasms
Pancreatic Neoplasms
Prostatic Neoplasms
Sarcoma
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Adenocarcinoma

Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on February 12, 2012