Clinical trial NCT00052507: Bortezomib in Treating Patients With Metastatic or Recurrent Colorectal Cancer
Official title: A Phase II Study Of PS-341 In Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
recurrent colon cancer
recurrent rectal cancer
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Bortezomib may interfere with the growth of tumor cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: Phase II trial to study the effectiveness of bortezomib in treating patients who have metastatic or recurrent colorectal cancer.

Detailed description: OBJECTIVES:

* Determine the efficacy of bortezomib, in terms of response rate and stable disease rate, in patients with recurrent or metastatic colorectal cancer.
* Determine the toxicity of this drug in these patients.
* Determine the time to progression and response duration in patients treated with this drug.
* Determine whether there is a relationship between levels of transcription factors NF kappa B and HIF-1 alpha and clinical outcome in patients treated with this drug.

OUTLINE: This is an open-label study.

Patients receive bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 21-41 patients will be accrued for this study within 2-4 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is incurable with conventional therapy

  * Metastatic or recurrent disease
* At least 1 unidimensionally measurable lesion
* At least 20 mm by conventional techniques or at least 10 mm by spiral CT scan
* Disease must be accessible to biopsy
* No known brain metastases

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-1 OR
* Karnofsky 70-100%

Life expectancy

* More than 3 months

Hematopoietic

* Absolute granulocyte count at least 1,500/mm\^3
* WBC at least 3,000/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic

* Bilirubin no greater than 1.25 times upper limit of normal (ULN)
* AST or ALT no greater than 3 times ULN (less than 5 times ULN if liver metastases present)

Renal

* Creatinine no greater than 1.25 times UNL OR
* Creatinine clearance at least 50 mL/min

Cardiovascular

* No symptomatic congestive heart failure
* No unstable angina pectoris
* No cardiac arrhythmia

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No psychiatric illness or social situation that would preclude study compliance
* No other uncontrolled concurrent illness
* No ongoing or active infection
* No other active malignancy within the past 3 years except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix
* No grade 1 or greater peripheral neuropathy due to prior chemotherapy
* No significant traumatic injury within the past 21 days

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No more than 1 line of prior chemotherapy (including any combination of fluorouracil, irinotecan, and/or oxaliplatin) for metastatic disease
* At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
* Prior adjuvant chemotherapy allowed
* No concurrent cytotoxic chemotherapy

Radiotherapy

* More than 4 weeks since prior radiotherapy and recovered
* No prior radiotherapy to measurable target lesion unless disease progression has occurred after radiotherapy
* No concurrent radiotherapy to the sole site of measurable disease

Surgery

* More than 21 days since prior major surgery

Other

* No other concurrent investigational agents
* No concurrent combination antiretroviral therapy for HIV-positive patients

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Cancer Care Ontario-Hamilton Regional Cancer Centre
state: Ontario
city: London
country: Canada
facility: Cancer Care Ontario-London Regional Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital at University Health Network
state: Ontario
Study officials:
affiliation: Princess Margaret Hospital, Canada
name: Amit M. Oza, MD
role: STUDY_CHAIR
References:
citation: Mackay H, Hedley D, Major P, Townsley C, Mackenzie M, Vincent M, Degendorfer P, Tsao MS, Nicklee T, Birle D, Wright J, Siu L, Moore M, Oza A. A phase II trial with pharmacodynamic endpoints of the proteasome inhibitor bortezomib in patients with metastatic colorectal cancer. Clin Cancer Res. 2005 Aug 1;11(15):5526-33. doi: 10.1158/1078-0432.CCR-05-0081.