Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00007347

Trial Description

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Title

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

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Trial Acronym

NEOLAP

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URL of the Trial

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Brief Summary in Lay Language

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.

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Brief Summary in Scientific Language

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.

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Organizational Data

  •   DRKS00007347
  •   2016/03/21
  •   2014/04/11
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Secondary IDs

  •   2013-004796-12 
  •   NCT02125136  (ClinicalTrials.gov)
  •   AIO-PAK-0113  (AIO-Studien-gGmbH)
  •   AX-CL-PANC-PI-003324 
  •   2013-004796-12 
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Health Condition or Problem studied

  •   Ductal Adenocarcinoma of the Pancreas
  •   C25 -  Malignant neoplasm of pancreas
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Interventions/Observational Groups

  •   Drug: Gem/nab-Pac
  •   Drug: FOLFIFINOX
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Treatment
  •   Parallel
  •   II
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Primary Outcome

- Conversion Rate; time frame: approx. 10 month; To compare the effect of intensified neoadjuvant chemotherapy on conversion rate to resectability in LAPC.

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Secondary Outcome

- Safety; time frame: approx. 22 month; 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
- objective tumour response rate; time frame: approx. 22 month; 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.
- disease control rate (DCR); time frame: approx. 22 month; assess disease control rate (DCR) after intensified neoadjuvant chemotherapy
- CA 19-9 change; time frame: 10 month; 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.
- R0 and R1 resections; time frame: 10 month; assess rate of R0 and R1 resections
- pathological responses; time frame: approx. 22 month; assess rate of grade 3 + 4 pathological responses according to grading scheme of treatment responses by Evans in resected patients.
- relapse-free survival (RFS); time frame: approx. 22 month; 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.
- Progression-free survival (PFS); time frame: approx. 2 years; 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.
- perioperative morbidity and mortality; time frame: 60 days; assess perioperative morbidity and mortality
- Tolerability; time frame: 10 month; evaluate safety and tolerability of intensified neoadjuvant chemotherapy (see safety measure)
- Overall Survival (OS); time frame: approx. 22 month; 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.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

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  •   2014/07/31
  •   168
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   75   Years
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Additional Inclusion Criteria

- 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-naìˆve 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.

- 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

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Exclusion Criteria

- 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

- 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

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Addresses

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    • AIO-Studien-gGmbH
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    • Celgene Corporation
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    • ClinAssess GmbH
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    • Universitätsklinikum Würzburg/Comprehensive Cancer Center Mainfranken
    • Kunzmann Volker, Prof. Dr. 
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    • Ralph Keller, Dipl.-Päd. 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   1
  •   2014/11/05
* This entry means the parameter is not applicable or has not been set.