A Phase II Feasibility Translational Research Trial of Induction Chemotherapy Followed by Concomitant Chemoradiation in Patients With Clinical T4 Rectal Cancer


Phase 2
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer

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Trial Information

A Phase II Feasibility Translational Research Trial of Induction Chemotherapy Followed by Concomitant Chemoradiation in Patients With Clinical T4 Rectal Cancer


OBJECTIVES:

- Determine the feasibility of obtaining a pre-treatment determination of intratumoral
molecular markers (TS, DPD, and ERCC-1) for use in selection of the appropriate regimen
for induction cytotoxic combination chemotherapy in patients with cT3-4 rectal
adenocarcinoma.

- Determine the response probability (unconfirmed, complete and partial) in patients
treated with targeted induction cytotoxic chemotherapy.

- Determine the toxicity of targeted induction cytotoxic chemotherapy and
chemoradiotherapy in these patients.

- Determine the response probability in these patients treated with chemoradiotherapy.

OUTLINE: This is a multicenter study.

- Induction chemotherapy: Patients are assigned to 1 of 3 treatment groups based on
molecular analysis of the pretreatment tumor specimen.

- Group I (lower likelihood of resistance to a fluorouracil-based regimen): Patients
receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours on
day 1 and fluorouracil IV over 46 hours beginning on day 1.

- Group II (higher likelihood of resistance to a fluorouracil-based regimen):
Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 90 minutes on
day 1.

- Group III (high likelihood of sensitivity to oxaliplatin and fluorouracil
therapy): Patients receive oxaliplatin IV over 90 minutes and leucovorin calcium
IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1.

Treatment in all groups repeats every 2 weeks for 4 courses in the absence of disease
progression or unacceptable toxicity.

Patients are evaluated for response approximately 2 weeks after the completion of induction
chemotherapy. Patients with stable disease or better receive chemoradiotherapy.

- Chemoradiotherapy: Beginning approximately 3 weeks after the completion of induction
chemotherapy, patients receive oral capecitabine twice daily continuously for 5 weeks
and concurrent radiotherapy once daily 5 days a week for 5 weeks.

After chemoradiotherapy, patients may undergo attempted surgical resection at the discretion
of the treating physician.

Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 10-65 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed primary adenocarcinoma of the rectum

- Locally advanced disease (clinical T3-4, N0-2, M0) based on at least 1 of the
following criteria:

- Clinically fixed tumors on rectal examination with tumor adherent to the pelvic
sidewall and/or sacrum

- Sciatica attributed to sacral root invasion with CT scan/MRI evidence of the
lack of clear tissue plane is considered evidence of fixation

- Hydronephrosis on CT scan or intravenous pyelogram of ureteric or bladder
invasion by cystoscopy and cytology or biopsy

- Invasion into the prostate, vagina, or uterus

- Transmural penetration of tumor through the muscularis propria as evidenced by CT
scan or MRI and endorectal ultrasound

- Distal border of the tumor must be at or below the peritoneal reflection (within 12
cm of the anal verge) by proctoscopic examination

- Measurable disease by x-ray, scans, or physical examination

- Available tumor tissue to determine molecular profile of the tumor before study
treatment

- No clinical evidence of high-grade (lumen diameter < 1 cm) large bowel obstruction
unless a diverting colostomy has been performed

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Zubrod 0-2

Life expectancy

- Not specified

Hematopoietic

- WBC ≥ 3,500/mm^3

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥100,000/mm^3

Hepatic

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- SGOT or SGPT ≤ 2.5 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

Renal

- See Disease Characteristics

- Creatinine ≤ 1.5 times ULN OR

- Estimated creatinine clearance > 50 mL/min

Cardiovascular

- No significant cardiac disease

- No recent myocardial infarction

Gastrointestinal

- See Disease Characteristics

- Able to swallow oral medication

- No active inflammatory bowel disease

Other

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix

- No prior unanticipated severe reaction to study drugs

- No known dihydropyrimidine dehydrogenase deficiency

- No serious uncontrolled infection

- No other serious medical illness that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- No prior chemotherapy for colon or rectal cancer

Endocrine therapy

- Not specified

Radiotherapy

- No prior pelvic radiotherapy

- No prior intra-operative radiotherapy or brachytherapy

- No concurrent intra-operative radiotherapy or brachytherapy

- No concurrent intensity-modulated radiotherapy

Surgery

- See Disease Characteristics

- See Radiotherapy

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response (confirmed and unconfirmed response, complete response, partial response)

Safety Issue:

No

Principal Investigator

Charles R. Thomas, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Texas Health Science Center at San Antonio

Authority:

United States: Federal Government

Study ID:

CDR0000334469

NCT ID:

NCT00070434

Start Date:

August 2004

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • stage II rectal cancer
  • stage III rectal cancer
  • adenocarcinoma of the rectum
  • Adenocarcinoma
  • Rectal Neoplasms
  • Colorectal Neoplasms

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