Clinical trial NCT00070434: S0304 Induct Chemo Then Chemo-RT in Pts w/Locally Advanced Adenocarcinoma of the Rectum
Official title: A Phase II Feasibility Translational Research Trial of Induction Chemotherapy Followed by Concomitant Chemoradiation in Patients With Clinical T4 Rectal Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage II rectal cancer
stage III rectal cancer
adenocarcinoma of the rectum
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-10-07
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as irinotecan, leucovorin, fluorouracil, and oxaliplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well different regimens of induction chemotherapy followed by chemoradiotherapy work in treating patients with locally advanced adenocarcinoma of the rectum.

Detailed description: 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.

Eligibility 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

Primary outcomes:
measure: Response (confirmed and unconfirmed response, complete response, partial response)
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Charles R. Thomas, MD
role: STUDY_CHAIR
affiliation: University of Southern California
name: Heinz-Josef Lenz, MD
role: STUDY_CHAIR
affiliation: University of Texas
name: Robert P. Whitehead, MD
role: STUDY_CHAIR
affiliation: M.D. Anderson Cancer Center
name: James L. Abbruzzese, MD
role: STUDY_CHAIR
affiliation: Radiation Oncology Center of Olathe
name: Stephen R. Smalley, MD
role: STUDY_CHAIR
affiliation: The University of Texas Health Science Center at San Antonio
name: Morton S. Kahlenberg, MD
role: STUDY_CHAIR
References: