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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02288195

Collaborator

Shantou Central Hospital (Other), Liaoning Tumor Hospital & Institute (Other), The First Affiliated Hospital with Nanjing Medical University (Other), Fujian Cancer Hospital (Other), Guangdong Provincial Hospital of Traditional Chinese Medicine (Other), First Affiliated Hospital of Chongqing Medical University (Other), The First Affiliated Hospital of Guangzhou Medical University (Other), Guangdong Provincial People's Hospital (Other), Cancer Hospital of Guangxi Medical University (Other), Meizhou People's Hospital (Other), Henan Cancer Hospital (Other), Affiliated Cancer Hospital of Shantou University Medical College (Other), Hubei Cancer Hospital (Other), The First Affiliated Hospital of Kunming Medical College (Other), Longyan City First Hospital (Other), Shengjing Hospital (Other), Zhejiang Cancer Hospital (Other), Jiangmen Central Hospital (Other), West China Hospital (Other), The Third Affiliated Hospital of Kunming Medical College. (Other)

663

Enrollment

Location

Arms

114.6

Anticipated Duration (Months)

5.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Rectal Neoplasms	Drug: Oxaliplatin Drug: capecitabine Radiation: Radiation	Phase 3

Detailed Description

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 Design

Study Type:

Interventional

Actual Enrollment :

663 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase III Study of Neoadjuvant Chemotherapy With Capecitabine and Oxaliplatin Versus Chemoradiation for Locally Advanced Rectal Cancer Patients

Actual Study Start Date :

Aug 13, 2014

Actual Primary Completion Date :

Mar 17, 2021

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chemotherapy Patients receive neoadjuvant chemotherapy comprising oxaliplatin 130mg/m² ivdrip over 2 hours on day 1,capecitabine 2000 mg/m² on days 1-14, treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.Patients without disease progression undergo low-anterior resection (LAR) with total mesorectal excision (TME) and 4 cycles of XELOX ( oxaliplatin 130mg/m² day 1，capecitabine 2000mg/m² days 1-14, repeated every 21 days). Patients with disease progression undergo chemoradiation as in group chemoradiotherapy before proceeding to LAR with TME.	Drug: Oxaliplatin 130 mg/m² iv drip over 2 hours on day 1, repeated every 21 days. Other Names: Eloxatin Drug: capecitabine 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. Other Names: Xeloda
Experimental: Chemoradiotherapy Patients receive capecitabine 825 mg/m² twice daily concurrently with radiation therapy for 5 days per week. Patients also undergo intensity-modulated radiation therapy 5 days a week for approximately 5.5 weeks. Patients then undergo LAR with TME and 4 cycles of XELOX ( oxaliplatin 130mg/m² day 1，capecitabine 2000mg/m² days 1-14, repeated every 21 days) .	Drug: capecitabine 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. Other Names: Xeloda Radiation: Radiation 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. Other Names: radiotherapy

Arm

Intervention/Treatment

Experimental: Chemotherapy

Patients receive neoadjuvant chemotherapy comprising oxaliplatin 130mg/m² ivdrip over 2 hours on day 1,capecitabine 2000 mg/m² on days 1-14, treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.Patients without disease progression undergo low-anterior resection (LAR) with total mesorectal excision (TME) and 4 cycles of XELOX ( oxaliplatin 130mg/m² day 1，capecitabine 2000mg/m² days 1-14, repeated every 21 days). Patients with disease progression undergo chemoradiation as in group chemoradiotherapy before proceeding to LAR with TME.

Drug: Oxaliplatin

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

Other Names:

Eloxatin

Drug: capecitabine

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.

Other Names:

Xeloda

Experimental: Chemoradiotherapy

Patients receive capecitabine 825 mg/m² twice daily concurrently with radiation therapy for 5 days per week. Patients also undergo intensity-modulated radiation therapy 5 days a week for approximately 5.5 weeks. Patients then undergo LAR with TME and 4 cycles of XELOX ( oxaliplatin 130mg/m² day 1，capecitabine 2000mg/m² days 1-14, repeated every 21 days) .

Drug: capecitabine

Other Names:

Xeloda

Radiation: Radiation

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.

Other Names:

radiotherapy

Outcome Measures

Primary Outcome Measures

Time to local recurrence [Up to 5 years]
the time interval between the date of randomization and the date of local or regional progression/relapse, or death, whichever occurred first.

Secondary Outcome Measures

Disease free survival [Up to 5 years]
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.
Pathologic complete response and tumor regression grade [Up to 18 weeks]
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)].
Pelvic R0 resection rate [Up to 18 weeks]
R0 resection: All gross disease has been removed, and microscopic examination reveals all surgical margins free of tumor.
Overall survival [Up to 5 years]
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.
Adverse event (AE) profiles [Up to 5 years]
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.
Rate of receiving pre-operative or post-operative chemoradiation [Up to 30 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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