STEM PACE - Stem cell Transplantation for Eradication of Minimal PAncreatic cancer persisting after surgical Excision

ISRCTN ISRCTN47877138
DOI https://doi.org/10.1186/ISRCTN47877138
EudraCT/CTIS number 2012-003528-19
Secondary identifying numbers 130311StemPace
Submission date
25/03/2013
Registration date
09/05/2013
Last edited
28/05/2020
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

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

Contact information

Dr Friedrich Hubertus Schmitz-Winnenthal
Scientific

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

Study information

Study designSingle-arm single-centre open phase-I/II trial using historical controls
Primary study designInterventional
Secondary study designNon randomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Scientific titleA phase-I/II study on the value of adjuvant allogeneic hematopoietic stem cell transplantation in pancreatic cancer after surgical resection
Study acronymSTEM PACE
Study objectivesThe principal question addressed is whether allo-HSCT can change the unfavourable natural course of pancreatic cancer.
Ethics approval(s)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
Health condition(s) or problem(s) studiedPancreatic cancer resected in curative intention (Adjuvant setting)
InterventionEligible 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 typeDrug
Pharmaceutical study type(s)
PhasePhase I/II
Drug / device / biological / vaccine name(s)allogeneic hematopoietic stem cell
Primary outcome measure2-year progression-free survival (PFS) from registration.
Secondary outcome measures1. 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 study start date01/05/2013
Completion date01/06/2016

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexNot Specified
Target number of participants12
Total final enrolment0
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment01/05/2013
Date of final enrolment01/06/2016

Locations

Countries of recruitment

  • Germany

Study participating centre

University of Heidelberg
Heidelberg
69120
Germany

Sponsor information

Ruprecht-Karls-University Heidelberg (Germany)
University/education

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

ROR logo "ROR" https://ror.org/038t36y30

Funders

Funder type

University/education

Heidelberg Surgery Foundation, University of Heidelberg (Germany)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol article protocol 10/03/2014 Yes No
Basic results 28/05/2020 No No

Editorial Notes

28/05/2020: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.