Bortezomib and Gemcitabine in Treating Older Patients With Advanced Solid Tumors

Breast Cancer Clinical Trial

Official title:

Phase I Study of Bortezomib and Gemcitabine in Elderly Patients With Solid Tumors (X05227)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00620295
• Other study ID #: CDR0000586510
• Secondary ID: UMN-2006LS040UMN
• Status: Completed
• Phase: Phase 1
• First received: February 20, 2008
• Last updated: November 27, 2017
• Start date: March 2007
• Est. completion date: October 2009

Study information

• Verified date: November 2017
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: October 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Carcinoma, Renal Cell
• Colorectal Cancer
• Colorectal Neoplasms
• Head and Neck Cancer
• Head and Neck Neoplasms
• Kidney Cancer
• Kidney Neoplasms
• Lung Cancer
• Lung Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Pancreatic Cancer
• Pancreatic Neoplasms
• Prostate Cancer
• Prostatic Neoplasms
• Sarcoma

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 21 (Week 3 - Cycle 1)
Secondary	Toxicity	Toxicity will be graded using the NCI's Common Terminology Criteria for Adverse Events (CTCAE 3.0)	30 Days after Last Treatment
Secondary	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.	Week 4
Secondary	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.	Pre-Dose