Colorectal CancerPhase 3PETACC-6NCT00766155
Chemotherapy and Radiation Therapy Before Surgery Followed by Capecitabine With or Without Oxaliplatin in Treating Patients With Locally Advanced Rectal Cancer
A Phase 3 study testing capecitabine and oxaliplatin in people with Colorectal Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- capecitabine and oxaliplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,094 participants
- Where
- No sites listed yet
- Study dates
- Aug 2008to Sep 2011
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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)
About this study
Official title: Preoperative Chemoradiotherapy and Postoperative Chemotherapy With Capecitabine and Oxaplatin vs.Capecitabine Alone in Locally Advanced Rectal Cancer (PETACC-6)
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.
Read the 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.
- Conditions
- Colorectal Cancer
- Being tested
- capecitabine, oxaliplatin
- Keywords
- stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum
- Medical subject headings
- Colorectal Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
capecitabineDrug
Given orally
oxaliplatinDrug
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Active comparator | 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. Receives: Drug: capecitabine |
| Arm II | Experimental | 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. Receives: Drug: capecitabine; Drug: oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free survival
Secondary outcomes (10)
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2008 (estimated)
- Study startAug 2008
- Primary completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 1,094 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Hans-Joachim Schmoll, MD, PhD, Study chair, Martin-Luther-Universität Halle-WittenbergKarin Haustermans, Study chair, U.Z. Gasthuisberg, Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00766155
- Sponsor's protocol ID
- EORTC-40054-22062
- Other IDs
- EU-20880, PETACC-6, ROCHE-EORTC-40054, 2006-006532-21
- Acronym
- PETACC-6
- Status last verified
- Oct 2016
- First submitted
- 2 Oct 2008
- Last updated
- 12 Oct 2016
- Results posted
- No
Publications
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.
PubMed 33001764
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preoperative Chemoradiotherapy and Postoperative Chemotherapy With Capecitabine and Oxaplatin vs.Capecitabine Alone in Locally Advanced Rectal Cancer (PETACC-6)
- ClinicalTrials.gov ID
- NCT00766155
- Acronym / sponsor ID
- PETACC-6 / EORTC-40054-22062
- Conditions
- Colorectal Cancer
- Keywords
- stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,094 participants (actual)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Study start
- Aug 2008
- Primary completion
- Sep 2011 (actual)
- First posted
- 3 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Active comparator | Drug: capecitabinePatients 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. |
| Arm II | Experimental | Drug: capecitabine, Drug: oxaliplatinPatients 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. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| capecitabineGiven orally | Drug | Arm I, Arm II |
| oxaliplatinGiven IV | Drug | Arm II |
Primary outcome
Disease-free survival
10 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2016.
- Derived from this study: PubMed 33001764Schmoll 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hans-Joachim Schmoll, MD, PhD study chair
Martin-Luther-Universität Halle-Wittenberg
Karin Haustermans study chair
U.Z. Gasthuisberg, Leuven
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing capecitabine and oxaliplatin in people with Colorectal Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free survival. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00766155, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2016.