Condition category
Cancer
Date applied
25/03/2013
Date assigned
09/05/2013
Last edited
18/03/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Pancreatic cancer is the third most common cancer related cause of death. Even in the 15% of patients who are eligible for surgical resection, less than 10% of patients surviving after 5 years. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established treatment capable of curing a variety of hematopoietic malignancies, taking advantage of the graft-versus-tumor effect (GVT). It works best when the underlying neoplasm has been turned into a stage of minimal disease by chemotherapy. There have been attempts of applying allo-HSCT to advanced solid tumors including pancreatic cancer with limited success but studies of allo-HSCT in solid tumors in minimal disease situations have never been performed. The aim of this study is to provide evidence for the clinical value of allo-HSCT in pancreatic cancer put into a minimal disease status by effective surgical resection and standard adjuvant chemotherapy. We want to find out if allo-HSCT can change the unfavourable natural course of this disease and whether allo-HSCT is able to provide long-term disease control to an extent otherwise not possible in pancreatic cancer and improve survival of affected patients.

Who can participate?
Patients with histologically proven diagnosis of pancreatic ductal adenocarcinoma having undergone radical resection (R1/R0 local resection) within the last 4-6 months at the University Hospital Heidelberg, who are matching the inclusion criteria.

What does the study involve?
Patients will undergo conditioning for allo-HSCT (fludarabine 30mg/mE2/d d -6 through d -2, cyclophosphamide 60mg/kg/d d-3 and d -2) followed by transplantation of allogeneic unmanipulated peripheral blood stem cells on d 0. Standard GVHD prophylaxis with CSA (target level 150-200; start d -1, taper d +60 onwards in the absence of GVHD) and MMF (2x1g; start d 0, stop d +30 in the absence of acute GVHD) will be instituted.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Clinic of General Surgery, Heidelberg (Germany)

When is the study starting and how long is it expected to run for?
From May 2012 to June 2016

Who is funding the study?
Heidelberg Surgery Foundation, University of Heidelberg (Germany)

Who is the main contact?
Klinisches Studienzentrum der Chirurgie (KSC)
ksc@med.uni-heidelberg.de

Trial website

Contact information

Type

Scientific

Primary contact

Dr Friedrich Hubertus Schmitz-Winnenthal

ORCID ID

Contact details

University of Heidelberg
Clinic of General Surgery
Im Neuenheimer Feld 110
Heidelberg
69120
Germany

Additional identifiers

EudraCT number

2012-003528-19

ClinicalTrials.gov number

Protocol/serial number

130311StemPace

Study information

Scientific title

A phase-I/II study on the value of adjuvant allogeneic hematopoietic stem cell transplantation in pancreatic cancer after surgical resection

Acronym

STEM PACE

Study hypothesis

The principal question addressed is whether allo-HSCT can change the unfavourable natural course of pancreatic cancer.

Ethics approval

Approved by the independent Medical Ethics Committee of the University of Heidelberg (EC) and the Paul-Ehrlich-Institute (PEI), as competent authority, 22/03/2013

Study design

Single-arm single-centre open phase-I/II trial using historical controls

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Pancreatic cancer resected in curative intention (Adjuvant setting)

Intervention

Eligible patients will be screened immediately after successful surgical resection, have a donor search initiated, and subjected to standard adjuvant chemotherapy.

Only those patients who underwent adjuvant chemotherapy without disease progression and who have a matched related stem cell donor available will be registered for the trial. Patients without a matched related donor will not be registered for the trial but may be used a historical control outside of the protocol.

Patients will undergo conditioning for allo-HSCT (fludarabine 30mg/mE2/d d -6 through d -2, cyclophosphamide 60mg/kg/d d-3 and d -2) followed by transplantation of allogeneic unmanipulated peripheral blood stem cells on d 0. Standard graft-versus-host disease (GVHD) prophylaxis with cyclosporine (CSA) (target level 150-200; start d -1, taper d +60 onwards in the absence of GVHD) and mycophenolate mofetil (MMF) (2x1g; start d 0, stop d +30 in the absence of acute GVHD) will be instituted.

Intervention type

Drug

Phase

Phase I/II

Drug names

allogeneic hematopoietic stem cell

Primary outcome measures

2-year progression-free survival (PFS) from registration.

Secondary outcome measures

1. 2-year PFS and overall survival (OS) after surgical resection
2. 2-year overall survival (OS) from registration
3. Minimal residual disease kinetics at screening day, registration day, 1, 3, 6, 12, 18 and 24 months according to study protocol (MRD; measured by tumor serum marker levels) and their correlation with immune events
4. Impact of important explanatory variables on PFS and OS.

Secondary feasibility endpoints
1. Non-relapse mortality (NRM) at 3 and 24 months after allo-HSCT
2. Prevalence of chronic graft-versus-host-disease at 6, 12 and 24 months from allo-HSCT
3. Quality of life at day -28, day +28, day +100, day +180, day +360, day +720 before/after allo-HSCT
4. Impact of important explanatory variables on NRM

Overall trial start date

01/05/2013

Overall trial end date

01/06/2016

Reason abandoned

Eligibility

Participant inclusion criteria

1. Histologically proven diagnosis of pancreatic ductal adenocarcinoma having undergone radical resection (R1/R0 local resection) within the last 4-6 months at the University Hospital Heidelberg
2. Hartwig score 1 or 2 (Millenium paper)
3. Measurable tumor serum marker (i.e. CA 19-9) prior to resection
4. Age at registration 18 to 65 years, either sex
5. Karnofsky index > /=70
6. Hematopoietic cell transplantation comorbidity index (HCT-CI) score 0-1 (pancreatic carcinoma does not count against the score)
7. HLA-identical (10/10 intermediate-resolution) related donor
8. Written informed consent, signed and dated

Participant type

Patient

Age group

Adult

Gender

Not Specified

Target number of participants

12

Participant exclusion criteria

1. Hartwig score ≤ 0 (Millenium paper)
2. HIV, HBV, HCV seropositivity
3. Organ dysfunction
4. Symptomatic coronary artery disease or ejection fraction <35%
5. DLCO ≤60%, FEV1 <65% of predicted FEV1 despite appropriate treatment or receiving supplementary continuous oxygen
6. Liver function abnormalities: Patients with will be excluded if total serum bilirubin >1.5 X ULN, or AST/ALT >2.5XULN
7. Chronic renal dysfunction defined by a creatinine clearance <50 ml/min.
8. Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment
9. Females who are pregnant or breastfeeding
10. Active other malignancies and/or a history of another malignancy treated by chemotherapy or radiotherapy within the last five years prior to inclusion
11. Patients with systemic, uncontrolled infections
12. Current alcohol or drug abuse
13. Inability to understand the scope of the study and intent of treatment. Dementia or altered mental status that would prohibit understanding informed consent
14. Participation in another interventional clinical trial according to the Arzneimittelgesetz within 30 days prior to inclusion

Recruitment start date

01/05/2013

Recruitment end date

01/06/2016

Locations

Countries of recruitment

Germany

Trial participating centre

University of Heidelberg
Heidelberg
69120
Germany

Sponsor information

Organisation

Ruprecht-Karls-University Heidelberg (Germany)

Sponsor details

Medical Faculty
c/o Ms. Irmtraut Gürkan
Heidelberg
69120
Germany

Sponsor type

University/education

Website

Funders

Funder type

University/education

Funder name

Heidelberg Surgery Foundation, University of Heidelberg (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2014 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/24612467

Publication citations

  1. Protocol

    Schmitz-Winnenthal FH, Schmidt T, Lehmann M, Beckhove P, Kieser M, Ho AD, Dreger P, Büchler MW, Stem cell Transplantation for Eradication of Minimal PAncreatic Cancer persisting after surgical Excision (STEM PACE Trial, ISRCTN47877138): study protocol for a phase II study., BMC Cancer, 2014, 14, 168, doi: 10.1186/1471-2407-14-168.

Additional files

Editorial Notes