CONVERT: Neoadjuvant Chemotherapy Alone Versus Preoperative Chemoradiation for Locally Advanced Rectal Cancer Patients

Sun Yat-sen University663 enrolled

Overview

Although neoadjuvant radiotherapy greatly decreases local recurrence in locally advanced rectal cancer patients undergoing surgery, it inevitably results in short-term and long-term toxicities. More importantly, it has not been confirmed that neoadjuvant radiotherapy could improve overall survival. The purpose of this study is to compare the effects of chemotherapy alone using a combination regimen known as XELOX (capecitabine and oxaliplatin ) and selective use of the standard treatment to the standard treatment of chemotherapy and radiation.

This randomised, open-label, multicentre,phase 3 trial began in August, 2014, as an adjuvant trial comparing capecitabine-based neoadjuvant chemoradiotherapy with chemotherapy alone,in patients aged 18 years to 75 with clinical stage II-III locally advanced rectal cancer from six Chinese institutions. Patients with local advanced rectal cancer (T2N+ or T3-4aNany,M0, CRM≥2mm, 12cm from the anus verge) were scheduled to Group A: receive neoadjuvant chemotherapy alone (4 cycles of XELOX: oxaliplatin 130mg/m2 day 1，capecitabine 2000mg/m2 days 1-14, repeated every 21 days) followed by radical surgery and 4 cycles of XELOX ( oxaliplatin 130mg/m2 day 1，capecitabine 2000mg/m2 days 1-14, repeated every 21 days) and Group B :chemoradiotherapy (50.4 Gy plus capecitabine 1650 mg/m² administered orally and concurrently with radiation therapy for 5 days per week.) followed by radical surgery and 6 cycles of XELOX ( oxaliplatin 130mg/m2 day 1，capecitabine 2000mg/m2 days 1-14, repeated every 21 days) The primary endpoint was 3-year local recurrence free survival; analyses were done based on all patients with post-randomization data.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

663

Interventions

OxaliplatinDRUG

130 mg/m² iv drip over 2 hours on day 1, repeated every 21 days.

capecitabineDRUG

825 mg/m² twice daily administered orally and concurrently with radiation therapy for 5 days per week. 1000 mg/m² po twice daily on days 1- 14 repeated every 21 days in Group A and adjuvant chemotherapy in Group B.

RadiationRADIATION

The total dosage was 46Gy consisted of 23 fractions of 2 Gy to clinical target volume without a boost dose and with the boost 4 Gy consisted of 2 fractions of 2 Gy to gross tumor volume by IMRT or 3D-CRT.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: DISEASE CHARACTERISTICS: * Diagnosis of rectal adenocarcinoma * Radiologically measurable or clinically evaluable disease * Tumor location within 12cm from anal verge * Clinical stage T2N+ or T3-4aNany,M0 Clinical staging should be estimated based on the combination of the following assessments: physical examination by the primary surgeon, CT scan of the chest/abdomen/pelvis, and a pelvic MRI with or without an endorectal ultrasound (ERUS) * No evidence that tumor is adjacent to (defined as within 2 mm of) the mesorectal fascia on pre-operative MRI * No tumor causing symptomatic bowel obstruction * No distant metastasis PATIENT CHARACTERISTICS: * ECOG performance status 0, 1 * White Blood Cell (WBC) ≥ 4,000/mm³ * Platelets ≥ 100,000/mm³ * Hemoglobin \> 10.0 g/dL * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST and ALT ≤ 1.5 times ULN * Creatinine ≤ 1.5 times ULN * No co-morbid illnesses or other concurrent disease that, in the judgment of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Exclusion Criteria: * Pregnant or nursing * Patient of child-bearing potential is not willing to employ adequate contraception * Not willing to return to enrolling medical site for all study assessments * With other invasive malignancy ≤ 5 years prior to registration; exceptions are colonic polyps, non-melanoma skin cancer, or carcinoma-in-situ of the cervix * Chemotherapy within 5 years prior to registration (hormonal therapy is allowable if the disease-free interval is ≥ 5 years) * Prior pelvic radiation

Outcomes

Primary Outcomes

Local-regional failure-free survival

the time interval between the date of randomization and the date of local or regional progression/relapse, or death, whichever occurred first.regional progression/relapse, or death, whichever occurred first.

Time frame: Up to 5 years

Secondary Outcomes

Disease free survival

the time interval between the date of randomization and the date of the first cancer-related event, second cancer, or death from any cause, whichever occurred first.

Time frame: Up to 5 years

Pathologic complete response and tumor regression grade

Pathological response will be made based on assessment of the surgical specimen at the primary treatment site. This assessment is made in addition to the AJCC 7th edition summary staging. A pCR must include no gross or microscopic tumor identified anywhere within the surgical specimen. This must include: * No evidence of malignant cells in the primary tumor specimen * No lymph nodes that contain tumor. The definition of a non-pCR will include any surgical specimen that has any evidence of residual tumor manifest in the primary or regional lymph nodes. For patients who do not meet criteria for a pCR, the extent of response to preoperative therapy will be graded using the Tumor Regression Grade (TRG) schema that is included in the AJCC 7th edition. This was also used by Rodel in the pre/postoperative rectal cancer study and was subsequently adopted by the AJCC \[Rodel (JCO 2005; 23:8688-8696)\].

Time frame: Up to 18 weeks

Pelvic R0 resection rate

R0 resection: All gross disease has been removed, and microscopic examination reveals all surgical margins free of tumor.

Time frame: Up to 18 weeks

Overall survival

the time interval between the date of randomization to the date of death. If the patient has been alive, the time until the last follow-up is taken as the overall survival period.

Time frame: Up to 5 years

Adverse event (AE) profiles

The severity of AE and the laboratory findings were graded by the investigators according to Common Terminology Criteria for Adverse Events, version 4. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0. A copy of the CTCAE version 4.0 can be downloaded from the CTEP web site: http://ctep.cancer.gov/protocolDevelopment/electronic\_applications/ctc.htm The maximum grade for each type of adverse events during neoadjuvant chemotherapy and chemoradiation therapy, and surgical complications will be recorded for each patient. Follow-up for patient safety should be done during the treatment period and 30 days after the end of the last cycle. The reason for the delay or interruption should be recorded on the CRF form.

Time frame: Up to 5 years

Rate of receiving pre-operative or post-operative chemoradiation

Time frame: Up to 30 weeks

CONVERT: Neoadjuvant Chemotherapy Alone Versus Preoperative Chemoradiation for Locally Advanced Rectal Cancer Patients

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes