Clinical trial NCT00031616: NB1011 in Treating Patients With Metastatic or Recurrent Colorectal Cancer
Official title: A Phase I/II Study Of NB1011 Administered Intravenously Daily For 5 Days Every 4 Weeks In Fluoropyrimidine-Resistant Metastatic Or Relapsed Colorectal Cancers
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
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: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I/II trial to study the effectiveness of NB1011 in treating patients who have metastatic or recurrent colorectal cancer that has not responded to previous treatment.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose of NB1011 in patients with fluoropyrimidine-resistant metastatic or recurrent colorectal cancer.
* Determine the safety and toxic effects of this drug in these patients.
* Determine the pharmacokinetics of this drug in these patients.
* Determine the efficacy of this drug in these patients.

OUTLINE: This is a phase I dose-escalation study followed by a phase II study.

* Phase I: Patients receive NB1011 IV over 1 hour on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of NB1011 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

* Phase II: Additional patients receive NB1011 at the MTD as in phase I. Patients are followed at day 30 and then for 5 months.

PROJECTED ACCRUAL: A maximum of 25 patients will be accrued for the phase I portion of this study. A total of 15-25 patients will be accrued for the phase II portion of this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed metastatic or recurrent colorectal adenocarcinoma that has progressed during or within 6 months of fluoropyrimidine-based therapy
* Prior treatment with irinotecan with or without fluorouracil
* Evaluable or measurable disease

  * Uni-dimensionally measurable disease allowed provided CEA is at least 2 times the upper limit of normal
* No meningeal or CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 70-100%

Life expectancy:

* At least 3 months

Hematopoietic:

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

Hepatic:

* Bilirubin less than 1.5 mg/dL (regardless of liver metastases)
* AST and ALT less than 1.5 times upper limit of normal (ULN) (3 times ULN if liver metastases present)
* PT and INR normal
* PTT normal

Renal:

* Creatinine less than 1.5 mg/dL OR
* Creatinine clearance greater than 50 mL/min

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* HIV negative
* No known hypersensitivity to NB1011 or any excipient or vehicle in its formulation
* No active or uncontrolled serious bacterial, viral, fungal, or parasitic infection
* No prior or concurrent alcohol abuse or dependency
* No other malignancy within the past 2 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
* No concurrent medical or psychological condition that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* See Disease Characteristics
* Recovered from prior anticancer chemotherapy
* No concurrent fluoropyrimidine-based or thymidylate synthase inhibitor agents

Endocrine therapy:

* Not specified

Radiotherapy:

* Recovered from prior anticancer radiotherapy
* No concurrent radiotherapy except palliative radiotherapy (to control a fracture or pain) provided index lesions are not involved

Surgery:

* Recovered from prior anticancer surgery

Other:

* At least 30 days since prior investigational agents
* No other concurrent anticancer therapy
* No concurrent disulfiram

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
Study officials:
affiliation: Jonsson Comprehensive Cancer Center
name: Mark D. Pegram, MD
role: STUDY_CHAIR
References: