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Ductal Adenocarcinoma of the PancreasPhase 2NEOLAPNCT02125136

Trial to Investigate Intensified Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Cancer

A Phase 2 study testing Gem/nab-Pac and FOLFIFINOX in people with Ductal Adenocarcinoma of the Pancreas, run by AIO-Studien-gGmbH at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The aim ot the study is to investigate the efficacy and safety of two new intensified chemotherapy regimens (gemcitabine (Gem)/nab- paclitaxel (PAC), FOLFIRINOX) as neoadjuvant chemotherapy protocol in locally advanced, non-metastatic pancreatic cancer (LAPC) and consecutive conversion of the tumor to resectability. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Ductal Adenocarcinoma of the Pancreas
What is being tested?
Gem/nab-Pac and FOLFIFINOX
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
168 participants
Where
1 siteGermany
Study dates
Nov 2014to 19 Feb 2020
Phase
Phase 2
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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult patients ≥ 18 years and ≤ 75 years of age
  • Histologic or cytologic proven ductal adenocarcinoma of the pancreas (histologic confirmation of diagnosis is preferred)
  • No distant metastases
  • De novo, treatment-naïve unresectable or borderline resectable LAPC; evaluation of unresectable and borderline resectable status according to NCCN- Clinical Practice Guidelines in Oncology "pancreatic adenocarcinoma" version 1.2013. Applicable criterion/criteria have to be indicated.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Total bilirubin ≤ 2 mg/dL. Patients with a biliary stent may be included provided that bilirubin level after stent insertion decreased to ≤ 2 mg/dL and there is no cholangitis.
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  • Adequate renal, hepatic and bone marrow function, defined as
  • Serum creatinine ≤ 1.25 x Upper limit of normal (ULN)
  • Calculated creatinine clearance ≥ 60 mL/min according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
  • Aspartate aminotransferase (AST)/(serum glutamic oxaloacetic transaminase)GOT and/or Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (GPT) ≤ 2.5 x ULN
  • Partial thromboplastin time (PTT) ≤ 1.5 x ULN and Quick value ≥ 70%
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Haemoglobin ≥ 8g/dL
  • Platelets ≥ 100 x 109/L
  • Females of childbearing potential (FCBP) must have a negative pregnancy test within 7 days of the first application of study treatment and must agree to use effective contraceptive birth control measures (Pearl Index < 1) during the course of the trial and for at least 1 month after last application of study treatment.
  • A female subject is considered to be of childbearing potential unless she is age ≥ 50 years and naturally amenorrhoeic for ≥ 2 year, or unless she is surgically sterile.
  • Males must agree not to father a child during the course of the trial and for at least 6 months after last administration of study drugs.
  • Signed and dated informed consent before the start of any specific protocol procedures
  • Patient's legal capacity to consent to study participation

Who cannot join

  • Evidence of distant metastases. In case of radiological suspicion of peritoneal carcinomatosis or ascites histological or cytological verification is required e.g. by means of exploratory laparoscopy
  • Local relapse of the pancreatic adenocarcinoma prior treated with surgical resection
  • Any previous treatment of the pancreatic carcinoma (radiotherapy, chemoradiotherapy, chemotherapy, targeted tumor therapy, local ablative therapy)
  • Contraindication for pancreas resection (pancreatic head resection, distal pancreatectomy with splenectomy, or complete pancreatectomy)
  • Larger surgical interventions within 4 weeks before study enrolment and/or diagnostic laparotomy with or without gastroenterostomy and with or without biliodigestive anastomosis within 2 weeks before first application of study treatment. Wound healing must be also completed before first application of study treatment.
  • Known chronic diarrhoea
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  • Peripheral polyneuropathy > grade 1
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency
  • Medical history of interstitial lung disease (ILD) or pulmonary fibrosis
  • Hypersensitivity against any of the study drugs (nab-paclitaxel, gemcitabine, oxaliplatin, irinotecan, 5-fluorouracil, folinic acid), or the ingredients of these drugs
  • Active or uncontrolled bacterial, viral, or fungal infection that requires systemic treatment
  • Known HIV- infection or active Hepatitis B virus (HBV)- or Hepatitis C virus (HCV) infection
  • Convulsion disorder that requires anticonvulsive treatment
  • Clinically significant cardiovascular or vascular disease or disorder ≤ 6 months before study enrolment (e.g. myocardial infarction, unstable angina pectoris, chronic heart failure New York Heart Association (NYHA) ≥ grade 2, uncontrolled arrhythmia, cerebral infarction)
  • Any other severe concomitant disease or disorder, which could influence patient's ability to participate in the study and his/her safety during the study or interfere with interpretation of study results e.g. severe hepatic, renal, pulmonary, metabolic, or psychiatric disorders
  • Requirement for concomitant antiviral treatment with sorivudine or brivudine
  • Requirement of immunosuppressive treatment
  • Continuing anticoagulant therapy with coumarin derivatives (treatment with low-molecular weight heparin allowed)
  • Continuing abuse of alcohol, drugs, or medical drugs
  • Pregnant or breast feeding females
  • Participation in any other clinical trial or treatment with any experimental drug within 28 days before enrolment to the study or during study participation until the end of treatment visit.
  • Previous or concurrent malignant tumor disease other than underlying tumor disease with the exception of cervical cancer in situ, adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, superficial bladder tumors (Ta,Tis, and T1) or any curatively treated tumors > 5 years prior to enrolment

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Universitätsklinikum Würzburg/Comprehensive Cancer Center Mainfranken

    Würzburg, Bavaria, 97080

Other trials in Germany

About this study

Official title: Prospective Randomized Multicenter Phase II Trial to Investigate Intensified Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Cancer

The aim ot the study is to investigate the efficacy and safety of two new intensified chemotherapy regimens (gemcitabine (Gem)/nab- paclitaxel (PAC), FOLFIRINOX) as neoadjuvant chemotherapy protocol in locally advanced, non-metastatic pancreatic cancer (LAPC) and consecutive conversion of the tumor to resectability.

Read the detailed description

This is a prospective open randomized multicenter phase II trial with two arms.

Patients suffering from histologically confirmed LAPC (and assessed as unresectable or borderline resectable according to National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines "pancreatic adenocarcinoma" version 1.2013) without metastases will receive two different neoadjuvant treatment regimens:

First all patients receive two cycles Gem/nab-PAC (duration of each cycle 28 days) as neoadjuvant chemotherapy in equal measure and a first restaging is performed after these two cycles based on imaging criteria. If there is no progression according to Response evaluation criteria in solid tumors (RECIST 1.1) criteria at the first restaging, the patients are randomized in a 1:1 relation to:

Two further cycles Gem/nab-PAC (duration of each cycle 28 days). or Four further cycles FOLFIRINOX (duration of each cycle 14 days). After the neoadjuvant chemotherapy a 2nd restaging is performed based on imaging criteria. All patients without progression at this restaging or at an earlier time point undergo obligatory exploratory laparotomy irrespective of imaging criteria to assess resectability. If they are evaluated as converted to resectable during this exploratory laparotomy, pancreas resection in curative intent will be performed. All patients with successful R0 or R1 pancreatic resection will receive three further cycles adjuvant chemotherapy with Gem/nab-PAC. Adjuvant chemotherapy will start within 4 to 8 weeks after pancreatic resection surgery.

Further treatment of patients with PD after 1st or 2nd restaging as well as patients with unresectable status based on exploratory laparotomy is under the discretion of the local investigators (e.g. second-line chemotherapy in case of distant relapse or local radiochemotherapy in case of local progression or definitive irresectability).

All patients are followed up for local recurrence, progression and survival until death or for at least one year after last application of study drugs whichever is sooner.

The translational research conducts exploratory analyses for potential biomarkers of possible prognostic or predictive value for efficacy of neoadjuvant chemotherapy in LAPC; including analyses of circulating tumor cells, molecular pathways of pancreatic adenocarcinoma including SPARC expression.

Being tested
Gem/nab-Pac, FOLFIFINOX
Keywords
unresectable, borderline resectable

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Gem/nab-PacDrug

    All patient receive:

    2 cycles gemcitabine/nab-paclitaxel ([Gem/nab-Pac]; duration of each cycle 28 days)

    Then:

    Nab-paclitaxel 125 mg/m2, IV infusion over 30 minutes, followed by gemcitabine 1000 mg/m2 as a 30-minute IV infusion on D1, D8, D15 of each 28-day cycle

  • FOLFIFINOXDrug

    All patient receive:

    2 cycles gemcitabine/nab-paclitaxel ([Gem/nab-Pac]; duration of each cycle 28 days)

    Then:

    Oxaliplatin 85 mg/m2, given as a 2-hour intravenous infusion D1 Folinic acid 400 mg/m2, given as a 2-hour intravenous infusion D1 Irinotecan 180 mg/m2, given as a 90-minutes intravenous infusion D1 (application through a Y-connector parallel to infusion of folinic acid or 30 minutes after start of folinic acid possible) Fluorouracil 400 mg/m2, administered by intravenous bolus, followed by a continuous intravenous infusion of fluorouracil 2400 mg/m2 over a 46-hour period D1.

    To be repeated on D1 of each cycle.

Study groups in NCT02125136
Study groupRoleWhat they receive
Gem/nab-PacExperimental2 further cycles Gem/nab-Pac (duration of each cycle 28 days)
Receives: Drug: Gem/nab-Pac
FOLFIFINOXExperimental4 cycles combination therapy with 5-fluorouracil/folinic acid, irinotecan, oxaliplatin (FOLFIFINOX) - duration of each cycle 14 days
Receives: Drug: FOLFIFINOX

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Conversion Rate

    To compare the effect of intensified neoadjuvant chemotherapy on conversion rate to resectability in LAPC.

    Measured: approx. 10 month

Secondary outcomes (11)

  1. Safety

    evaluate safety and tolerability of intensified neoadjuvant chemotherapy

    • Exposure to study drugs
    • Type, incidence, and severity of adverse events
    • Dose reduction or discontinuation of study drugs due to adverse events
    • Laboratory parameters

    Measured: approx. 22 month

  2. objective tumour response rate

    assess objective tumour response rate (ORR) to intensified neoadjuvant chemotherapy Baseline tumor measurement(s) will be performed within 4 weeks before the first dose of study drug with either computed tomography (CT) including spiral CT or MRI according to investigator's choice and clinical practice at the respective trial site as done routinely also outside of clinical trial situations.The same method used at baseline must be used consistently for response assessment to neoadjuvant chemotherapy at the first restaging (after the first part of neoadjuvant chemotherapy) and the second restaging (after the second part of neoadjuvant chemotherapy) and thereafter.

    Measured: approx. 22 month

  3. disease control rate (DCR)

    assess disease control rate (DCR) after intensified neoadjuvant chemotherapy

    Measured: approx. 22 month

  4. CA 19-9 change

    Assess carbohydrate antigen 19-9 (CA 19-9) change during/after neoadjuvant chemotherapy. In this trial, CA 19-9 change to neoadjuvant chemotherapy will be evaluated as decrease to the baseline level at the 1st and 2nd restaging.

    Measured: 10 month

  5. R0 and R1 resections

    assess rate of R0 and R1 resections

    Measured: 10 month

  6. pathological responses

    assess rate of grade 3 + 4 pathological responses according to grading scheme of treatment responses by Evans in resected patients.

    Measured: approx. 22 month

  7. relapse-free survival (RFS)

    assess relapse-free survival (RFS): Relapse-free survival is the time from Day 1 after pancreatic resection to the date of relapse, defined as Day 1 after pancreatic resection to either local relapse of pancreatic cancer or occurrence of distant metastases. For each patient who is not known to have had a relapse as of the data-inclusion cut-off date for a particular analysis, time to relapse will be censored for that analysis at the date of the patient's last study visit prior to that cut-off date.

    Measured: approx. 22 month

  8. Progression-free survival (PFS)

    PFS is the time from Day 1 of the first cycle of neoadjuvant chemotherapy to date of objective disease progression or to death of any cause.

    For each patient who is not known to have had a progression as of the data-inclusion cut-off date for a particular analysis, time to progressive disease will be censored for that analysis at the date of the patient's last study visit prior to that cut-off date.

    Measured: approx. 2 years

  9. perioperative morbidity and mortality

    assess perioperative morbidity and mortality

    Measured: 60 days

  10. Tolerability

    evaluate safety and tolerability of intensified neoadjuvant chemotherapy (see safety measure)

    Measured: 10 month

  11. Overall Survival (OS)

    OS is the time from Day 1 of the first cycle of neoadjuvant chemotherapy to date of death from any cause.

    The rate of patients who have died from any cause after one year and two years, respectively will be assessed. For each patient for whom it is not known whether he died or is still alive until the data-inclusion cut-off date for a particular analysis, time to death of any cause will be censored for that analysis at the date of the patient's last study visit prior to that cut-off date.

    Measured: approx. 22 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Apr 2014 (estimated)
  2. Study startNov 2014
  3. Primary completion1 Mar 2019
  4. Study completion19 Feb 2020

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
168 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02125136
Sponsor's protocol ID
AIO-PAK-0113
Other IDs
AX-CL-PANC-PI-003324, 2013-004796-12
Acronym
NEOLAP
Status last verified
Dec 2021
First submitted
11 Apr 2014
Last updated
15 Dec 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • Surendran SA, Guenther M, Nemati N, Incera ML, Zhang D, Boeck S, Heinemann V, Kimmel B, Kunzmann V, Ormanns S. Circulating free bacterial DNA as a novel biomarker for monitoring therapy response in patients with advanced pancreatic cancer. Eur J Cancer. 2026 Sep 10;247:117040. doi: 10.1016/j.ejca.2026.117040. Online ahead of print.

    PubMed 42743886

  • Hartlapp I, Valta-Seufzer D, Siveke JT, Algul H, Goekkurt E, Siegler G, Martens UM, Waldschmidt D, Pelzer U, Fuchs M, Kullmann F, Boeck S, Ettrich TJ, Held S, Keller R, Anger F, Germer CT, Stang A, Kimmel B, Heinemann V, Kunzmann V; German Pancreatic Cancer Group (AIO-PAK) and NEOLAP investigators. Prognostic and predictive value of CA 19-9 in locally advanced pancreatic cancer treated with multiagent induction chemotherapy: results from a prospective, multicenter phase II trial (NEOLAP-AIO-PAK-0113). ESMO Open. 2022 Aug;7(4):100552. doi: 10.1016/j.esmoop.2022.100552. Epub 2022 Aug 12.

    PubMed 35970013

  • Kunzmann V, Siveke JT, Algul H, Goekkurt E, Siegler G, Martens U, Waldschmidt D, Pelzer U, Fuchs M, Kullmann F, Boeck S, Ettrich TJ, Held S, Keller R, Klein I, Germer CT, Stein H, Friess H, Bahra M, Jakobs R, Hartlapp I, Heinemann V; German Pancreatic Cancer Working Group (AIO-PAK) and NEOLAP investigators. Nab-paclitaxel plus gemcitabine versus nab-paclitaxel plus gemcitabine followed by FOLFIRINOX induction chemotherapy in locally advanced pancreatic cancer (NEOLAP-AIO-PAK-0113): a multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2021 Feb;6(2):128-138. doi: 10.1016/S2468-1253(20)30330-7. Epub 2020 Dec 16.

    PubMed 33338442

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Gem/nab-Pac and FOLFIFINOX in people with Ductal Adenocarcinoma of the Pancreas, run by AIO-Studien-gGmbH at 1 site in Germany.

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 19 inclusion and 22 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: finished, as of the sponsor's last update on 15 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Conversion Rate (time frame: approx. 10 month). 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 NCT02125136, which also lists 3 linked publications.

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 15 Dec 2021.

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