S0304 Induct Chemo Then Chemo-RT in Pts w/Locally Advanced Adenocarcinoma of the Rectum

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00070434
• Other study ID #: CDR0000334469
• Secondary ID: U10CA032102S0304
• Status: Withdrawn
• Phase: Phase 2
• First received: October 3, 2003
• Last updated: June 5, 2012
• Start date: August 2004

Study information

• Verified date: June 2012
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Colorectal Cancer

Intervention

Drug:
• capecitabine
825mg/m2 BID, PO, daily
• fluorouracil
Bolus + IV for 46 hrs on Day 1
• irinotecan hydrochloride
IV infusion over 90 min on Day 1
• leucovorin calcium
200mg/m2 IV 2 hour infusion on Day 1
• oxaliplatin
85mg/m2 IV infusion for 90minutes on Day 1

Radiation:
• radiation therapy
Original Planning Target Volume (PTV1): The total dose to the prescription point shall be 4500 cGy in 25 fractions (Monday - Friday inclusive). Boost Planning Target Volume (PTV2): The cumulative dose within the boost volume to the prescription point shall be 5,040 - 5,400 cGy (per Section 7.5b). Daily Dose: The daily dose to the prescription point of the original and boost volumes shall be 180 cGy. Fractionation: Treatment shall be given 5 days/week. All radiation fields shall be treated once daily.

Drug:
• Pyridoxine
50mg TID, PO daily

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response (confirmed and unconfirmed response, complete response, partial response)			No