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Chemotherapy and Radiation Therapy Before Surgery Followed by Capecitabine With or Without Oxaliplatin in Treating Patients With Locally Advanced Rectal Cancer (PETACC-6)

Primary Purpose

Colorectal Cancer

Status

Completed

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

capecitabine

oxaliplatin

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the rectum
- Tumor ≤ 12 cm from the anal verge
- Stage T3-4 or any node-positive disease
No evidence of metastatic disease (confirmed by negative CT scan of the chest and abdomen)
Resectable disease or expected to become resectable after preoperative chemoradiation
May only be randomized once in this trial

PATIENT CHARACTERISTICS:

WHO/ECOG performance status 0-2
Hemoglobin ≥ 10.0 g/dL (transfusion allowed to achieve or maintain levels)
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
ALT and AST ≤ 2.5 times upper level of normal (ULN)
Alkaline phosphatase ≤ 2.5 times ULN
Total bilirubin ≤ 1.5 times ULN
Creatinine clearance > 50 mL/min
Creatinine ≤ 1.5 times ULN
Able to swallow tablets
No prior or concurrent malignancies within the past 5 years except for adequately treated cone-biopsied carcinoma in situ of the cervix or basal cell carcinoma of the skin
No clinically significant (i.e., active) cardiac disease, including any of the following:
- Congestive heart failure
- Symptomatic coronary artery disease
- Cardiac arrhythmia
No myocardial infarction within the past 12 months
No known significant impairment of intestinal resorption (e.g., chronic diarrhea, inflammatory bowel disease)
No pre-existing conditions that would preclude chemoradiotherapy or radiotherapy (i.e., fistulas, severe ulcerative colitis [particularly patients currently taking sulfasalazine], Crohn's disease, or prior adhesions)
No peripheral neuropathy ≥ grade 2 by CTCAE v3.0
No serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease
No history of uncontrolled seizures, central nervous system disorders or psychiatric disability that, in the opinion of the principal investigator, is clinically significant and would preclude giving informed consent or interfere with compliance with oral drug administration
No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

No prior cytotoxic chemotherapy or radiation therapy for rectal cancer
No prior radiation therapy to the pelvis
No prior or concurrent investigational drug, agent, or procedure
More than 4 weeks since prior participation in the active or follow-up period of another investigational protocol
No known allergy or any other adverse reaction to any of the study drugs or to any related compound
No known dihydropyrimidine dehydrogenase deficiency
No organ allograft requiring immunosuppressive therapy
No concurrent sorivudine or chemically related analogues (e.g., brivudine)

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm I

Arm II

Arm Description

Patients receive oral capecitabine twice daily and undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33. Patients may receive additional chemoradiotherapy on days 36-38. Patients then undergo surgery. Beginning 4-8 weeks after surgery, patients receive capecitabine twice daily on day 1-15. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients receive oral capecitabine twice daily and undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33. Patients also receive oxaliplatin IV over 1 hour on days 1, 8, 15, 22, and 29 prior to radiotherapy followed by surgery. Patients may receive additional chemoradiotherapy on days 36-38. Beginning 4-8 weeks later, patients receive oxaliplatin IV over 2 hours on day 1, and oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Disease-free survival

Secondary Outcome Measures

Overall survival within at least the first 5 years after treatment

Loco-regional failure, defined as local or regional recurrence, inoperable disease, or R1 or R2 resection

Distant failure (i.e., distant metastasis)

Pathological down-stage (ypT0, 2N0) rate

Pathological complete remission (ypT0N0) rate

Tumor regression grade

Histopathological R0 resection rate

Sphincter preservation rate

Preoperative complication rate

Toxicity according to CTCAE v.3.0 weekly during treatment, at 4-8 weeks after surgery, at therapy completion, and every 6 months for 5 years after therapy completion

Full Information

NCT ID

NCT00766155

First Posted

October 2, 2008

Last Updated

October 11, 2016

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

1. Study Identification

Unique Protocol Identification Number

NCT00766155

Brief Title

Chemotherapy and Radiation Therapy Before Surgery Followed by Capecitabine With or Without Oxaliplatin in Treating Patients With Locally Advanced Rectal Cancer

Acronym

PETACC-6

Official Title

Preoperative Chemoradiotherapy and Postoperative Chemotherapy With Capecitabine and Oxaplatin vs.Capecitabine Alone in Locally Advanced Rectal Cancer (PETACC-6)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2016

Overall Recruitment Status

Completed

Study Start Date

August 2008 (undefined)

Primary Completion Date

September 2011 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

4. Oversight

5. Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy that uses a 3-dimensional image of the tumor to help focus thin beams of radiation directly on the tumor may kill more tumor cells and have fewer side effects. Giving chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether capecitabine is more effective with or without oxaliplatin in treating patients with rectal cancer. PURPOSE: This randomized phase III trial is studying giving chemotherapy together with radiation therapy before surgery followed by capecitabine with or without oxaliplatin to see how well it works in treating patients with locally advanced rectal cancer.

Detailed Description

OBJECTIVES: Primary Investigate whether the addition of oxaliplatin to neoadjuvant chemoradiotherapy and adjuvant chemotherapy comprising capecitabine improves disease-free survival in patients with locally advanced rectal cancer. Secondary Compare the overall survival of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy and adjuvant chemotherapy comprising capecitabine with versus without oxaliplatin. Determine the loco-regional failure and distant failure of patients treated with these regimens. Determine the pathological down-staging (ypT0-2N0) of patients treated with these regimens. Determine the pathological complete remission (yp T0N0) rate of patients treated with these regimens. Determine the tumor progression grade and histopathological R0 resection of patients treated with these regimens. Determine the sphincter preservation rate of patients treated with these regimens. Determine the perioperative complication rate of these regimens in these patients. Determine the toxicity of these regimens in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to treating center, clinical T category (T1-3 vs T4), clinical nodal status (Nx vs NO vs N1-2), distance from the tumor to the anal verge (≤ 5 cm vs > 5 cm) and method of locoregional staging (EUS+MRI vs EUS+CTscan vs MRI alone). Patients are randomized to 1 of 2 treatment arms. Arm I (control): Neoadjuvant therapy: Patients receive oral capecitabine twice daily on days 1-35. Patients also undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33 followed by surgery. Patients may receive additional chemoradiotherapy on days 36-38. Adjuvant therapy: Beginning 4-8 weeks after surgery, patients receive oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Arm II (investigational): Neoadjuvant therapy: Patients receive oral capecitabine twice daily and undergo concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33. Patients also receive oxaliplatin IV over 1 hour on days 1, 8, 15, 22, and 29 prior to radiotherapy followed by surgery. Patients may receive additional chemoradiotherapy on days 36-38. Adjuvant therapy: Beginning 4-8 weeks after surgery, patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed every 3 months for 3 years, and then every 6 months for 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer

Keywords

stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1094 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I

Arm Type

Active Comparator

Arm Description

Arm Title

Arm II

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

capecitabine

Intervention Description

Given orally

Intervention Type

Drug

Intervention Name(s)

oxaliplatin

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

Disease-free survival

Secondary Outcome Measure Information:

Title

Overall survival within at least the first 5 years after treatment

Title

Loco-regional failure, defined as local or regional recurrence, inoperable disease, or R1 or R2 resection

Title

Distant failure (i.e., distant metastasis)

Title

Pathological down-stage (ypT0, 2N0) rate

Title

Pathological complete remission (ypT0N0) rate

Title

Tumor regression grade

Title

Histopathological R0 resection rate

Title

Sphincter preservation rate

Title

Preoperative complication rate

Title

Toxicity according to CTCAE v.3.0 weekly during treatment, at 4-8 weeks after surgery, at therapy completion, and every 6 months for 5 years after therapy completion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility Criteria

DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the rectum Tumor ≤ 12 cm from the anal verge Stage T3-4 or any node-positive disease No evidence of metastatic disease (confirmed by negative CT scan of the chest and abdomen) Resectable disease or expected to become resectable after preoperative chemoradiation May only be randomized once in this trial PATIENT CHARACTERISTICS: WHO/ECOG performance status 0-2 Hemoglobin ≥ 10.0 g/dL (transfusion allowed to achieve or maintain levels) ANC ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 ALT and AST ≤ 2.5 times upper level of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN Total bilirubin ≤ 1.5 times ULN Creatinine clearance > 50 mL/min Creatinine ≤ 1.5 times ULN Able to swallow tablets No prior or concurrent malignancies within the past 5 years except for adequately treated cone-biopsied carcinoma in situ of the cervix or basal cell carcinoma of the skin No clinically significant (i.e., active) cardiac disease, including any of the following: Congestive heart failure Symptomatic coronary artery disease Cardiac arrhythmia No myocardial infarction within the past 12 months No known significant impairment of intestinal resorption (e.g., chronic diarrhea, inflammatory bowel disease) No pre-existing conditions that would preclude chemoradiotherapy or radiotherapy (i.e., fistulas, severe ulcerative colitis [particularly patients currently taking sulfasalazine], Crohn's disease, or prior adhesions) No peripheral neuropathy ≥ grade 2 by CTCAE v3.0 No serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease No history of uncontrolled seizures, central nervous system disorders or psychiatric disability that, in the opinion of the principal investigator, is clinically significant and would preclude giving informed consent or interfere with compliance with oral drug administration No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: No prior cytotoxic chemotherapy or radiation therapy for rectal cancer No prior radiation therapy to the pelvis No prior or concurrent investigational drug, agent, or procedure More than 4 weeks since prior participation in the active or follow-up period of another investigational protocol No known allergy or any other adverse reaction to any of the study drugs or to any related compound No known dihydropyrimidine dehydrogenase deficiency No organ allograft requiring immunosuppressive therapy No concurrent sorivudine or chemically related analogues (e.g., brivudine)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hans-Joachim Schmoll, MD, PhD

Organizational Affiliation

Martin-Luther-Universität Halle-Wittenberg

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Karin Haustermans

Organizational Affiliation

U.Z. Gasthuisberg, Leuven

Official's Role

Study Chair

12. IPD Sharing Statement

Citations:

PubMed Identifier

33001764

Citation

Schmoll HJ, Stein A, Van Cutsem E, Price T, Hofheinz RD, Nordlinger B, Daisne JF, Janssens J, Brenner B, Reinel H, Hollerbach S, Caca K, Fauth F, Hannig CV, Zalcberg J, Tebbutt N, Mauer ME, Marreaud S, Lutz MP, Haustermans K. Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD. J Clin Oncol. 2021 Jan 1;39(1):17-29. doi: 10.1200/JCO.20.01740. Epub 2020 Oct 1.

Results Reference

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Chemotherapy and Radiation Therapy Before Surgery Followed by Capecitabine With or Without Oxaliplatin in Treating Patients With Locally Advanced Rectal Cancer

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