DJ-927 as Second-Line Therapy in Treating Patients With Progressive Locally Advanced or Metastatic Colorectal Adenocarcinoma

RATIONALE: Drugs used in chemotherapy, such as DJ-927, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well DJ-927 works as second-line therapy in treating patients with progressive locally advanced or metastatic colorectal adenocarcinoma (cancer).

OBJECTIVES:

Primary

* Determine the objective tumor response rate in patients with progressive locally advanced or metastatic adenocarcinoma of the colon or rectum treated with DJ-927 as second-line treatment.

Secondary

* Determine the duration of response in patients treated with this drug.
* Determine the time to tumor progression in patients treated with this drug.
* Determine the median survival time in patients treated with this drug.
* Determine the quantitative and qualitative toxic effects of this drug in these patients.
* Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is an open-label, multicenter study. Patients are stratified according to prior first-line treatment regimen (irinotecan-containing vs oxaliplatin-containing).

Patients receive oral DJ-927\* on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: \*Patients receive 1 of 2 selected doses to confirm the previously established maximum tolerated dose

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 56-62 patients (28-31 per stratum) will be accrued for this study within 12 months.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed adenocarcinoma of the colon or rectum

  * Progressive locally advanced or metastatic disease
* Received 1 prior irinotecan- or oxaliplatin-containing regimen
* At least 1 measurable lesion

  * Target lesion must be outside field of prior radiotherapy
* No symptomatic brain metastases

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-2

Life expectancy

* At least 3 months

Hematopoietic

* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3

Hepatic

* ALT and AST ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
* Bilirubin ≤ 1.5 times ULN

Renal

* Creatinine ≤ 1.5 times ULN

Gastrointestinal

* No difficulty with swallowing
* No malabsorption
* No diarrhea (excess of 2-3 stools/day above normal frequency) within the past month
* No history of chronic diarrhea

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* HIV negative
* No concurrent serious infection
* No other concurrent severe or uncontrolled underlying medical condition that would preclude study participation
* No neuropathy ≥ grade 2
* No history of any severe or life-threatening hypersensitivity reaction
* No psychiatric disorder that would preclude study compliance
* No other malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent biologic therapy

Chemotherapy

* See Disease Characteristics
* At least 4 weeks since prior myelosuppressive chemotherapy and recovered
* No other concurrent chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* See Disease Characteristics
* At least 4 weeks since prior radiotherapy and recovered
* No concurrent radiotherapy

  * Localized radiotherapy to non-indicator lesions for pain relief allowed provided other methods of pain control are ineffective

Surgery

* At least 4 weeks since prior major surgery and recovered
* No prior major surgery in the stomach or small intestine

Other

* More than 28 days since prior investigational agents (including analgesics and/or antiemetics)
* No other concurrent anticancer therapy
* No other concurrent cytotoxic therapy
* No concurrent grapefruit products