Neoplasms

Digestive System Diseases

All Conditions

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Oxaliplatin

Leucovorin

Fluorouracil

Levoleucovorin

Aflibercept

Folic Acid

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Vitamin B Complex

Trace Elements

Angiogenesis Inhibitors

Growth Inhibitors

Folinic Acid

Folate

Vitamin B9

Preoperative Chemoradiation: (6 weeks)

* 5-FU: 225 mg/m2 per day by intravenous continuous infusion (IVCI), Days 1 thru 42;
* Radiation: 50.4 Gy (1.8 Gy/day or 28 fractions) Mon thru Fri, Weeks 1 thru 6;
* Aflibercept: 4 mg/ kg, via IV infusion, Days 1 and 15.

Surgery at least 6 weeks after last day of aflibercept: Patients will undergo abdominoperineal or low anterior resection with total mesorectal excision, per standard treatment guidelines.

Postoperative Chemotherapy and Aflibercept Treatments (four 28-day cycles):

* Aflibercept (administered first): 4 mg/kg IV for approximately 1 hour (no more than 2 hours) on Days 1 and 15 of each cycle.
* Modified FOLFOX6:

  * Leucovorin: 400 mg/m2 as a 2-hour infusion prior to 5-FU on Days 1 and 15 of each cycle.
  * Oxaliplatin: 85 mg/m2 IV as a 2-hour infusion prior to 5-FU on Days 1 and 15 of each cycle.
  * 5-FU: 400-mg/m2 bolus for 2 to 4 minutes followed by 2400 mg/m2 for 46 hours on Days 1 and 15 of each cycle.

Radiation

Abdominoperineal or low anterior resection with total mesorectal excision, per standard treatment guidelines

Surgery

FOLFOX6

Johanna C Bendell, M.D.

The purpose of this Phase II study will be to investigate the antiangiogenic agent, aflibercept, in combination with chemoradiation as preoperative treatment for patients with stage II/III rectal cancer, followed by 4 months of FOLFOX6 plus aflibercept adjuvantly.

5-FU, Aflibercept, and Radiation (RT) for Preoperative and Postoperative Patients With Stage II/III Rectal Cancer

A Phase II Study of 5-Fluorouracil (5-FU), Aflibercept, and Radiation for the Preoperative and Adjuvant Treatment of Patients With Stage II/III Rectal Cancer

The Pathologic Complete Response (pCR) Rate is defined as the number of pathologic complete responders among all patients evaluable for response, including evaluable patients who did not proceed to surgery. A pCR is defined as the absence of any residual abnormality detected in a pathological specimen.

Measured from date of first protocol treatment until date of death.

The probability of overall survival at 6 months and 12 months from date of first protocol treatment until date of death.

The percentage of patients who had Low Anterior Resection during surgery..

The probability of disease free survival at 6 and 12 months after initiating protocol treatment.

Adverse events and serious adverse events (AEs and SAEs) were graded according to National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE) v4.0. Specific AE and SAE terms are provided in the Adverse Event module.

Sanofi

SCRI Development Innovations, LLC

All patients who received at least one dose of protocol treatment during the trial.

Preoperative Chemoradiation: 5-FU: 225 mg/m2 per day by intravenous continuous infusion (IVCI), Days 1 thru 42; Radiation: 50.4 Gy (1.8 Gy/day or 28 fractions) Mon thru Fri, Weeks 1 thru 6; Aflibercept: 4 mg/ kg, via IV infusion, Days 1 and 15.

Surgery: Patients will undergo abdominoperineal or low anterior resection with total mesorectal excision, per standard treatment guidelines.

Postoperative Chemotherapy and Aflibercept Treatments:

Aflibercept (administered first): 4 mg/kg IV for approximately 1 hour (no more than 2 hours) on Days 1 and 15 of each cycle.

Modified FOLFOX6:

* Leucovorin: 400 mg/m2 as a 2-hour infusion prior to 5-FU on Days 1 and 15 of each cycle.
* Oxaliplatin: 85 mg/m2 IV as a 2-hour infusion prior to 5-FU on Days 1 and 15 of each cycle.
* 5-FU: 400-mg/m2 bolus for 2 to 4 minutes followed by 2400 mg/m2 for 46 hours on Days 1 and 15 of each cycle.

Radiation

Aflibercept

Surgery: Abdominoperineal or low anterior resectio

FOLFOX6/Aflibercept/Radiation/Surgery

Preoperative Chemoradiation (6 weeks) Surgery (6 weeks from last dose of aflibercept) Postoperative Chemotherapy and aflibercept (four 28-day cycles)

FOLFOX6/Aflibercept/Radation/Surgery

Age, Continuous

Gender

White/Caucasian

Black/African American

Race/Ethnicity, Customized

United States

Region of Enrollment

Stage II

Stage III

Eligible patients with a histologically confirmed diagnosis of Stage II or Stage III rectal cancer, staged according to the American Joint Committee on Cancer (AJCC) Staging Manual - Edition 7.

Carcinoma Stage at Initial Diagnosis

ECOG Performance Status = 0

ECOG Performance Status = 1

Eastern Cooperative Oncology Group (ECOG) Performance Status

0=Fully active, able to carry on all pre-disease performance without restriction

1. Restricted in physically strenuous activity. Ambulatory and able to carry out work of a light or sedentary nature
2. Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3. Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4. Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
5. Dead

Baseline ECOG Performance Status

Well differentiated

Moderately differentiated

Poorly differentiated

Could not be assessed

Histologic Grade at Baseline

Charles Davis, RAC

All patients enrolled in the trial who were evaluable for pathologic response. Four patients were not evaluable for response.

Pathologic Complete Response Rate

Overall Survival

6-month OS probability

12 month OS probability

Overall Survival Probability at 6 and 12 Months

Sphincter Preservation Rate

Disease-Free Survival

6-month DFS probability

12-month DFS probability

Disease Free Survival Probability at 6 and 12 Months

SAEs

All patients who received at least one dose of protocol treatment.

The Number of Participants Who Experienced Serious or Non-Serious Adverse Events as a Measure of Safety.

Preoperative Chemoradiation (6 weeks): 5-FU: 225 mg/m2 per day by intravenous continuous infusion (IV), Days 1-42; Radiation: 50.4 Gy (1.8 Gy/day) Mon-Fri, Weeks 1 thru 6; Aflibercept: 4 mg/ kg, via IV infusion, Days 1 and 15.

Surgery (6 weeks from last dose of aflibercep): abdominoperineal or low anterior resection with total mesorectal excision, per standard treatment guidelines.

Postoperative Chemotherapy and Aflibercept: Aflibercept (administered first): 4 mg/kg IV for approximately 1 hour; Days 1 and 15 of each 28-day cycle; Modified FOLFOX6: Leucovorin: 400 mg/m2 as a 2-hour infusion prior to 5-FU on Days 1 and 15 of each cycle; Oxaliplatin: 85 mg/m2 IV as a 2-hour infusion prior to 5-FU on Days 1 and 15 of each cycle; 5-FU: 400-mg/m2 bolus for 2 to 4 minutes followed by 2400 mg/m2 for 46 hours on Days 1 and 15 of each cycle.

Overall Study

Spots Global Cancer Trial Database for 5-FU, Aflibercept, and Radiation (RT) for Preoperative and Postoperative Patients With Stage II/III Rectal Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial