Concurrent Chemo-Radiotherapy Versus Radiotherapy With Boost in Locally Advanced Unresectable Rectal Cancers

Concurrent Chemo-Radiotherapy vs Radiotherapy With Boost in Locally Advanced Unresectable Rectal Cancers. A Randomized Phase II Study

At Tata Memorial Hospital 50% of the patients present in the locally advanced stage which is technically unresectable, or that is beyond the realm of a potentially curative surgical resection. The evaluation of treatment approaches for these tumors is hampered by the absence of any substantial randomized studies and the heterogeneous nature of the tumors at presentation.

The management of these tumors has changed over the years, there is emphasis on neoadjuvant chemoradiation therapy, trying to convert a tumor that is initially unresectable to one that is potentially curable by surgery. But only 70-80% of the patients are able to complete this treatment without any significant treatment breaks.

Dose escalated treatment with radiotherapy in locally advanced and unresectable rectal cancers have been tried in many small series with good results and lesser toxicity.

Comparison outcome between the two arms will indicate the relative efficacy and toxicity of neoadjuvant concurrent chemoradiation vs boosted radiotherapy alone in downstaging of advanced cancers.

Study Overview

• Status: Unknown
• Conditions: Rectal Cancer
• Intervention / Treatment: Radiation: Additional Radiation boost to the primary tumor volume; Drug: Chemoradiation

Detailed Description

Aims/ Objectives

1. To compare the resectability rate when patients are treated when conventional chemoradiation to patients treated with radiation alone with an additional boost to the primary tumor in case of unresectable rectal cancers.
2. To study the treatment toxicity and local control rate.

Study methodology This is a phase II Randomised controlled study. Ninety cases of advanced rectal cancer (Stage II - Stage III) will be divided in two equal groups (Arm I & II) Arm-1(standard arm) - Patients will receive standard external radiation therapy to pelvis + concurrent chemotherapy with Tab Capecitabine. This will be followed by surgery at 6-8 weeks if deemed resectable.

Arm-2 (research arm) Patients in this group will not receive any neo-adjuvant chemotherapy, instead they will receive radiotherapy alone additional dose of localized radiotherapy boost. This will be followed by surgery at 6-8 weeks if deemed resectable.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Tata Memorial Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with measurable disease, medically able to undergo pelvic surgery.
2. Patients with unresectable adenocarcinoma of the rectum located up to 12 cm from the anal verge without evidence of distant metastases.
3. Patients must be 18 years old or greater.
4. Patients with clinical stage T3 orT4 based on endorectal ultrasound or physical exam.
5. Patients with lab values within standard protocol parameters
6. Karnofsky performance status > 60.
7. No history of other malignancies within 5 years, except non-melanoma skin cancer, in situ carcinoma of the cervix or ductal carcinoma of the breast. Previous invasive cancer permitted if disease-free at least 5 years
8. Patient must sign study-specific consent prior to randomization.

Exclusion Criteria:

1. Any evidence of distant metastasis
2. Synchronous primary colon carcinomas, except T1 lesions
3. Prior radiation therapy to the pelvis
4. Prior chemotherapy for malignancies
5. Pregnancy or lactation.
6. Serious, uncontrolled, concurrent infection(s).
7. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months.
8. Evidence of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.
9. Other serious uncontrolled medical conditions that the investigator feels might compromise study participation.
10. Major surgery within 4 weeks of the study treatment.
11. Lack of physical integrity of the upper gastrointestinal tract or mal-absorption syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm 2 (Radiation + boost ); Radiation dose to pelvis will be delivered at 1.8 Gy per day, five days per week, to give a total of 25 fractions over a period of five weeks for a total of 45 Gy. Boost Field - Will be given to all the patients in the radiotherapy alone followed by surgery arm. The boost will be given with by 3dimensional conformal radiotherapy to a dose of 15-20 Gy. After 45Gy the boost will be planned on the original tumor volume.	Radiation: Additional Radiation boost to the primary tumor volume; 15-20Gy; Other Names: Radiation Boost
Active Comparator: Arm 1 (standard) Chemoradiation; The Radiation dose will be delivered at 1.8 Gy per day, five days per week, to give a total of 25 fractions over a period of five weeks for a total of 45 Gy. Chemotherapy will begin on the first day of radiotherapy and continue until the completion of radiotherapy. Capecitabine will be administered orally daily 2000 mg/m2 in two divided doses (approximately 12 hours apart) for 2 weeks followed by a 1-week rest period given as 3 week cycles.	Drug: Chemoradiation; Chemotherapy will begin on the first day of radiotherapy and continue until the completion of radiotherapy. Capecitabine will be administered orally daily 2000 mg/m2 in two divided doses (approximately 12 hours apart) for 2 weeks followed by a 1-week rest period given as 3 week cycles.; Other Names: Capebine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparison of resectability rate of in the two groups at 6-8 weeks following radiotherapy.	3 years
Side effects and other adverse effects in the two groups during radiotherapy and up to 2 years post radiotherapy.	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Comparison of pathological downstaging between the two groups who undergo surgery.	3 years

Collaborators and Investigators

• Sponsor: Tata Memorial Hospital
• Investigators: Principal Investigator: Reena Engineer, MD, Tata Memorial Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Anticipated): February 1, 2009
• Study Completion (Anticipated): July 1, 2009

Study Registration Dates

• First Submitted: December 12, 2008
• First Submitted That Met QC Criteria: December 12, 2008
• First Posted (Estimate): December 15, 2008

Study Record Updates

• Last Update Posted (Estimate): December 15, 2008
• Last Update Submitted That Met QC Criteria: December 12, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: Unresectable rectal cancers
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: 260

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No