Pancreatic CancerPhase 3NCT01314027
Adjuvant Versus Neoadjuvant Plus Adjuvant Chemotherapy in Resectable Pancreatic Cancer
A Phase 3 study testing Neoadjuvant Chemotherapy with gemcitabine/oxaliplatin and adjuvant chemotherapy with gemcitabine in people with Pancreatic Cancer, run by University of Zurich at 5 sites in 4 countries.
Trial summary
The outcome of patients with resected pancreatic cancer has significantly been improved by adjuvant chemotherapy. However, a large proportion of patients cannot receive adjuvant chemotherapy due to surgical complications. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- Neoadjuvant Chemotherapy with gemcitabine/oxaliplatin and adjuvant chemotherapy with gemcitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 5 sitesin 4 countries
- Study dates
- Sep 2009to May 2019
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- resectable adenocarcinoma of the pancreatic head (requiring duodeno-pancreatectomy)
- T1-3, Nx, M0 (UICC 6th version, 2002)
- infiltration of the portal vein (<180°) is not an exclusion criterion
- cytologic or histologic confirmation of adenocarcinoma
- age >18 years
- written informed consent
Who cannot join
- contraindication for Whipple procedure
- an infiltration >180° of the portal vein
- abutment of the tumor to the superior mesenteric artery
- infiltration of the superior mesenteric artery or the celiac trunk
- chronic neuropathy > grade 2
- WHO performance score >2
Show all 12Show fewer
- uncorrectable cholestasis (bilirubin > 100mmol/l despite drainage attempts for more than four weeks prior to inclusion)
- female patients in child bearing age not using adequate contraception (oral or subcutaneous contraceptives, intrauterine pessary (IUP), condoms)
- pregnant or lactating women
- mental or organic disorders which could interfere with giving informed consent or receiving treatments
- Second malignancy diagnosed within the past 5 years, except non-melanomatous skin cancer or non-invasive cervical cancer
- percutaneous biopsy of the primary tumor
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
France2 sites
University Hospital of Marseille
Marseille
University Hospital of Strasbourg
Strasbourg
About this study
Official title: Adjuvant Gemcitabine Versus NEOadjuvant Gemcitabine/Oxaliplatin Plus Adjuvant Gemcitabine in Resectable PAncreatic Cancer: a Randomized Multicenter Phase III Study (NEOPAC Study)
The outcome of patients with resected pancreatic cancer has significantly been improved by adjuvant chemotherapy. However, a large proportion of patients cannot receive adjuvant chemotherapy due to surgical complications. Neoadjuvant chemotherapy has been shown to be safe and effective and can be applied to all patients. This study should test neoadjuvant chemotherapy in a randomized manner.
Patients with resectable cytologically proven adenocarinoma of the pancreatic head are randomized to arm A or B.
Read more
Patients randomized to arm A receive an 8-week neoadjuvant chemotherapy with gemcitabine/oxaliplatin followed by surgery. Thereafter, all patients receive adjuvant gemcitabine for six months.
Patients randomized to arm B undergo surgery and receive the same adjuvant treatment as in arm A.
The primary study-endpoint is the recurrence-free survival. Tumor recurrence are determined by computed tomography in a defined protocol.
- Trial with medicinal product
Read the detailed description
Due to the improvement in the recurrence-free and overall survival by adjuvant chemotherapy, surgery followed by adjuvant chemotherapy is currently considered the standard treatment for resectable pancreatic cancer. However, a significant proportion (>25%) of patients cannot receive adjuvant treatment due to the morbidity of pancreas surgery. Neoadjuvant (preoperative) chemotherapy appears particularly attractive since it can be applied to all patients and has resulted in a significant histological tumor response with a median survival superior to adjuvant chemotherapy in a recent prospective phase II trial.
The aim of this study is to determine the role of neoadjuvant chemotherapy in patients with resectable pancreatic cancer.Eligible patients are randomized to:
arm A: neoadjuvant chemotherapy + resection + adjuvant chemotherapy arm B: resection + adjuvant chemotherapy Neoadjuvant chemotherapy consists of gemcitabine (1000mg/m2) and oxaliplatin (100mg/m2) on days 1, 15, 29 and 43, while adjuvant chemotherapy is based on gemcitabine 1000mg/m2 for 6 months.
If the restaging protocol excludes distant metastases, a diagnostic laparoscopy is performed, followed by a Whipple operation in the absence of distant metastases.
The primary study end-point is the recurrence-free survival after study inclusion, and this is defined by the interval between the date of written informed consent until recurrence. Secondary end-points are the overall survival and the surgical complication rate. Interim analyses are performed after the inclusion of 100 and 200 patients without interrupting patient accrual. An independent data monitoring committee will review the results of each interim analysis and will decide about the study cessation or continuation.
Patients will be followed-up according to the protocol below in order to assess tumor recurrence.
Quality of life will be assessed by the QLQ-30 questionnaire of the EORTC at study entry, after neoadjuvant chemotherapy, start and end of the adjuvant chemotherapy and at each follow-up study visit. Representative histological samples are reviewed and stored by the reference pathologist at the University Hospital of Zurich. These samples will also be used to determine the histological response and extent of cytopathic effects. Furthermore, the nutritional status is assessed from all patients by the prealbumin serum levels at study entry and prior to surgery. Further translational research is desired and will be individually organized by each center.
- Conditions
- Pancreatic Cancer
- Being tested
- Neoadjuvant Chemotherapy with gemcitabine/oxaliplatin, adjuvant chemotherapy with gemcitabine
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neoadjuvant Chemotherapy with gemcitabine/oxaliplatinDrug
Also called gemcitabine, eloxatin
Patients with resectable cytologically proven adenocarinoma of the pancreatic head are randomized to arm A or B.
Patients randomized to arm A receive an 8-week neoadjuvant chemotherapy with gemcitabine/oxaliplatin. Thereafter, surgery is performed if the restaging does not reveal a contraindication. Finally, all patients receive adjuvant gemcitabine for six months.
adjuvant chemotherapy with gemcitabineDrug
Patients randomized to arm B undergo surgery and receive the same adjuvant treatment as in arm A.
| Study group | Role | What they receive |
|---|---|---|
| neoadjuvant + adjuvant chemotherapy | Experimental | neoadjuvant chemotherapy is based on gemcitabine/oxaliplatin adjuvant therapy is based on gemcitabine Receives: Drug: Neoadjuvant Chemotherapy with gemcitabine/oxaliplatin |
| adjuvant chemotherapy | Active comparator | adjuvant therapy is based on gemcitabine Receives: Drug: adjuvant chemotherapy with gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
by computed tomography
Measured: 9 months after inclusion
Secondary outcomes (5)
Progression-free survival
by computer tomography
Measured: 12, 15, 21, 27, 33, 39, ... months after inclusion
histological response
Histology
Measured: Pancreatic resection
overall survival
Measured: 1, 3 and 5 years after inclusion
complication rates after surgery
Measured: 60 days postoperative
feasibility of adjuvant chemotherapy
Measured: within 8 postoperative weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2011 (estimated)
- Study startSep 2009
- Primary completionDec 2018
- Study completionMay 2019
Why it stopped: low recruitment
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 Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by University of ZurichThe 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
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre-Alain Clavien, MD, PhD, Study director, UniversitaetsSpital Zuerich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01314027
- Sponsor's protocol ID
- NEOPAC
- Status last verified
- Jul 2019
- First submitted
- 29 Sep 2010
- Last updated
- 25 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Heinrich S, Pestalozzi B, Lesurtel M, Berrevoet F, Laurent S, Delpero JR, Raoul JL, Bachellier P, Dufour P, Moehler M, Weber A, Lang H, Rogiers X, Clavien PA. Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study). BMC Cancer. 2011 Aug 10;11:346. doi: 10.1186/1471-2407-11-346.
PubMed 21831266
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjuvant Gemcitabine Versus NEOadjuvant Gemcitabine/Oxaliplatin Plus Adjuvant Gemcitabine in Resectable PAncreatic Cancer: a Randomized Multicenter Phase III Study (NEOPAC Study)
- ClinicalTrials.gov ID
- NCT01314027
- Acronym / sponsor ID
- NEOPAC
- Conditions
- Pancreatic Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low recruitment
- Enrolment
- 38 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- Dec 2018 (actual)
- Study completion
- May 2019 (actual)
- First posted
- 14 Mar 2011 (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.
The outcome of patients with resected pancreatic cancer has significantly been improved by adjuvant chemotherapy. However, a large proportion of patients cannot receive adjuvant chemotherapy due to surgical complications. Neoadjuvant chemotherapy has been shown to be safe and effective and can be applied to all patients. This study should test neoadjuvant chemotherapy in a randomized manner.
Patients with resectable cytologically proven adenocarinoma of the pancreatic head are randomized to arm A or B.
Patients randomized to arm A receive an 8-week neoadjuvant chemotherapy with gemcitabine/oxaliplatin followed by surgery. Thereafter, all patients receive adjuvant gemcitabine for six months.
Patients randomized to arm B undergo surgery and receive the same adjuvant treatment as in arm A.
The primary study-endpoint is the recurrence-free survival. Tumor recurrence are determined by computed tomography in a defined protocol.
- Trial with medicinal product
Detailed description
Due to the improvement in the recurrence-free and overall survival by adjuvant chemotherapy, surgery followed by adjuvant chemotherapy is currently considered the standard treatment for resectable pancreatic cancer. However, a significant proportion (>25%) of patients cannot receive adjuvant treatment due to the morbidity of pancreas surgery. Neoadjuvant (preoperative) chemotherapy appears particularly attractive since it can be applied to all patients and has resulted in a significant histological tumor response with a median survival superior to adjuvant chemotherapy in a recent prospective phase II trial.
The aim of this study is to determine the role of neoadjuvant chemotherapy in patients with resectable pancreatic cancer.Eligible patients are randomized to:
arm A: neoadjuvant chemotherapy + resection + adjuvant chemotherapy arm B: resection + adjuvant chemotherapy Neoadjuvant chemotherapy consists of gemcitabine (1000mg/m2) and oxaliplatin (100mg/m2) on days 1, 15, 29 and 43, while adjuvant chemotherapy is based on gemcitabine 1000mg/m2 for 6 months.
If the restaging protocol excludes distant metastases, a diagnostic laparoscopy is performed, followed by a Whipple operation in the absence of distant metastases.
The primary study end-point is the recurrence-free survival after study inclusion, and this is defined by the interval between the date of written informed consent until recurrence. Secondary end-points are the overall survival and the surgical complication rate. Interim analyses are performed after the inclusion of 100 and 200 patients without interrupting patient accrual. An independent data monitoring committee will review the results of each interim analysis and will decide about the study cessation or continuation.
Patients will be followed-up according to the protocol below in order to assess tumor recurrence.
Quality of life will be assessed by the QLQ-30 questionnaire of the EORTC at study entry, after neoadjuvant chemotherapy, start and end of the adjuvant chemotherapy and at each follow-up study visit. Representative histological samples are reviewed and stored by the reference pathologist at the University Hospital of Zurich. These samples will also be used to determine the histological response and extent of cytopathic effects. Furthermore, the nutritional status is assessed from all patients by the prealbumin serum levels at study entry and prior to surgery. Further translational research is desired and will be individually organized by each center.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| neoadjuvant + adjuvant chemotherapy | Experimental | Drug: Neoadjuvant Chemotherapy with gemcitabine/oxaliplatinneoadjuvant chemotherapy is based on gemcitabine/oxaliplatin adjuvant therapy is based on gemcitabine |
| adjuvant chemotherapy | Active comparator | Drug: adjuvant chemotherapy with gemcitabineadjuvant therapy is based on gemcitabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- resectable adenocarcinoma of the pancreatic head (requiring duodeno-pancreatectomy)
- T1-3, Nx, M0 (UICC 6th version, 2002)
- infiltration of the portal vein (<180°) is not an exclusion criterion
- cytologic or histologic confirmation of adenocarcinoma
- age >18 years
Key exclusion criteria (12 listed)
- contraindication for Whipple procedure
- an infiltration >180° of the portal vein
- abutment of the tumor to the superior mesenteric artery
- infiltration of the superior mesenteric artery or the celiac trunk
- chronic neuropathy > grade 2
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 |
|---|---|---|
| Neoadjuvant Chemotherapy with gemcitabine/oxaliplatinAlso: gemcitabine, eloxatinPatients with resectable cytologically proven adenocarinoma of the pancreatic head are randomized to arm A or B. Patients randomized to arm A receive an 8-week neoadjuvant chemotherapy with gemcitabine/oxaliplatin. Thereafter, surgery is performed if the restaging does not reveal a contraindication. Finally, all patients receive adjuvant gemcitabine for six months. | Drug | neoadjuvant + adjuvant chemotherapy |
| adjuvant chemotherapy with gemcitabinePatients randomized to arm B undergo surgery and receive the same adjuvant treatment as in arm A. | Drug | adjuvant chemotherapy |
Primary outcome
Progression-free survival
Time frame: 9 months after inclusion
by computed tomography
5 secondary outcomes
Progression-free survival
Time frame: 12, 15, 21, 27, 33, 39, ... months after inclusion
histological response
Time frame: Pancreatic resection
overall survival
Time frame: 1, 3 and 5 years after inclusion
complication rates after surgery
Time frame: 60 days postoperative
feasibility of adjuvant chemotherapy
Time frame: within 8 postoperative weeks
Results and safety
The study was stopped early (reason given: low recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2019.
- Derived from this study: PubMed 21831266Heinrich S, Pestalozzi B, Lesurtel M, Berrevoet F, Laurent S, Delpero JR, Raoul JL, Bachellier P, Dufour P, Moehler M, Weber A, Lang H, Rogiers X, Clavien PA. Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study). BMC Cancer. 2011 Aug 10;11:346. doi: 10.1186/1471-2407-11-346.
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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.
Pierre-Alain Clavien, MD, PhD study director
UniversitaetsSpital Zuerich
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Neoadjuvant Chemotherapy with gemcitabine/oxaliplatin and adjuvant chemotherapy with gemcitabine in people with Pancreatic Cancer, run by University of Zurich at 5 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. 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: stopped early, as of the sponsor's last update on 25 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France, Belgium, Germany, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
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 was stopped early (reason given: low recruitment). Results are not available in the source record.
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?
Progression-free survival (time frame: 9 months after inclusion). 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 NCT01314027, 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 25 Jul 2019.