CY-503 for the Treatment of Chemotherapy-refractory Metastatic Colorectal Cancer - Full Text View

Sponsors and Collaborators:	Cytavis Biopharma GmbH ClinAssess GmbH Medizinische Univ. Insbruck - Koordinierungszentrum für Klinische Studien (KKS) Charité Universitätsmedizin Berlin - Institut für Medizinische Immunologie
Information provided by:	Cytavis Biopharma GmbH
ClinicalTrials.gov Identifier:	NCT00932724

Purpose

This trial is designed as a phase II evaluation of the effect of CY-503 or placebo on progression free survival (PFS) defined as the time from start of treatment until the objective observation of progressive disease (PD) or death from any course in patients with chemotherapy-refractory metastatic colorectal cancer.

Condition	Intervention	Phase
Metastatic Colorectal Cancer	Drug: CY-503 Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Phase II Double-blind Placebo-controlled Trial of CY503 in Patients With Chemotherapy-refractory Metastatic Colorectal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

U.S. FDA Resources

Further study details as provided by Cytavis Biopharma GmbH:

Primary Outcome Measures:

Tumor assessment by using CT scans and/or MRIs [ Time Frame: every 8 weeks (each 2 cycles) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Assessment of Adverse Events [ Time Frame: every 4 weeks (every cycle) ] [ Designated as safety issue: Yes ]
Assessment of quality of life using a standardized questionaire [ Time Frame: every 4 weeks (every cycle) ] [ Designated as safety issue: No ]
Assessment of survival by "physical exem" [ Time Frame: every 4 weeks (every cycle) / every 3 months during follow-up ] [ Designated as safety issue: No ]

Estimated Enrollment:	250
Study Start Date:	July 2009
Estimated Study Completion Date:	November 2012
Estimated Primary Completion Date:	November 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
CY-503: Experimental	Drug: CY-503 Ampoules with 1 ml 350 ng CY-503 solution for s.c. injection twice weekly. One cycle is defined as 4 consecutive weeks
Placebo: Placebo Comparator	Drug: Placebo Ampoules with 1 ml placebo solution for s.c. injection twice weekly. One cycle is defined as 4 consecutive weeks

Detailed Description:

Colorectal cancer has a worldwide annual incidence of approximately 1 million new cases diagnosed yearly and it is the second leading cause of cancer-related death in Western nations. There are a couple of approved standard therapies for the treatment of MCRC with cytotoxic agents irinotecan, oxaliplatin, and the fluoropyrimidines , as well as bevacizumab, the antibody against vascular endothelial growth factor A, and cetuximab, the antibody against the epidermal growth factor receptor. But there are only a few studies achieving a median survival time of more than 20 months in MCRC patients with standard regimens. After a 1st line therapy a high proportion (50% to 80%) of patients receives a 2nd line therapy with drugs not used in 1st line therapy and a part of them gets a 3rd line treatment. Results from a 2nd line therapy are best response rates ranging from 4 % - 23 %, a median PFS rate of 5.1 months, a median TTP of 4.1 - 4.6 months and median overall survival 6.9 - 12 months. However, for patients who experience disease progression after standard therapy (definition see inclusion criteria) there is no further standard therapeutic option. These patients developed a resistance to these therapies and finally die of their disease. They generally get best supportive care (BSC). Thus, there is a need for new active treatment options in this setting.

In this phase II double-blind placebo-controlled trial the efficacy and safety of CY-503, 350 ng s.c. injected in patients with chemotherapy refractory MCRC are tested. Approved treatments given to MCRC patients are usually discontinued after a treatment over some weeks at the first detection of objective PD. It will be tested if CY-503 is able to achieve progression-free-survival (PFS) in comparison to placebo. Patients will initially be included to receive either CY-503 or placebo until documentation of objective PD.

Standard therapy must be finished and has shown objective PD. Also patients with contraindications to standard therapy can be included.

CY-503 shows the potential to improve treatment of MCRC. This study aims at evaluating the activity and therapeutic effects of the substance. Anticipated capabilities are substitution of cytostatic drugs or improvement of their efficacy and tolerability . Furthermore, the expected improvement of PFS rates after failure of standard chemotherapies has to be investigated.

In a phase I trial CY-503 showed SD in patients who had exhausted standard therapy options for metastatic disease with subsequent disease progression with a median TTP of 17.4 weeks.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Age ≥ 18 years
Patients with histologically documented metastatic colorectal adeno-carcinoma and tumor progression while on or within 3 months after termination of chemotherapy
Patients who are refractory or intolerant to at least one of the following treatment regimens (defined as standard therapy) or who have clear contraindications to: 5-FU/Capecitabine + Oxaliplatin/Irinotecan ± Bevacizumab or Cetuximab or Panitumumab, or Irinotecan - patients are regarded to be refractory, if tumor progression was documented during or within the first three months after standard therapy
No chemotherapy within 4 weeks before treatment start
No residual significant toxicity (greater than NCI grade 1)
No signs or symptoms of peripheral neuropathy within 4 weeks before treatment start
No investigational treatment within 4 weeks before treatment start and during the trial
Patients must use effective contraception if of reproductive potential. Females must not be pregnant or lactating
Eastern Cooperative Oncology Group (ECOG) Performance status of 0 - 2
WBC ≥ 3,000/mm3, absolute neutrophil count (ANC) ≥ 1,500/mm3, platelet count ≥100,000/mm3
Bilirubin ≤ 1.5 mg/dL (25.65 μmol/L) (unless due to Gilbert's syndrome in which case the bilirubin should be
- 3.5 mg/dL (59.86 μmol/L)), aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 3 × upper limit of normal (ULN); hepatic alkaline phosphatase ≤ 3.0 × ULN (in case of liver metastases higher levels do not hinder inclusion of patients)
Serum creatinine ≤ 1.5 mg/dL (132.60 μmol/L), proteinuria < 2.0 g/24 hr urine collection in patients with a positive urine dipstick for protein
Written informed consent according to ICH-GCP and national laws and regulations prior to receipt of any trial medication or beginning trial procedures

Exclusion Criteria:

Evidence of any other malignant disease (with the exception of tumours operatively cured at least 5 years prior to the trial)
Known brain metastases
Uncontrolled pleural effusions
Interstitial pneumonitis or pulmonary fibrosis
Severe/ unstable systemic disease or infection and circumstances not permitting trial participation (e.g., alcoholism or substance abuse)
Unstable cardiac disease in the last 6 months
Use of conventional mistletoe preparations, any immunostimulating substances, monoclonal antibodies and/or colony stimulating factors within four weeks prior to and during the trial - ongoing therapy with steroids is permitted if the dose is not higher than 20 mg of predni-sone-equivalent at the time of inclusion and during this clinical trial
Any evidence or history (elicited by the investigator) of symptomatic cerebrovascular events (i.e., stroke or transient ischemic attack) within 6 months prior to randomization
Any history or evidence of pulmonary embolism or thrombophlebitis (including deep vein thrombosis) requiring anticoagulant therapy (e.g., marcumar or heparin)
History of hypersensitivity to mistletoe
History of primary immunodeficiency
Known human immunodeficiency virus (HIV) or known active viral hepatic infections
Prior treatment with CY-503
A general medical or psychological condition or behaviour, including substance dependence or abuse that, in the opinion of the investigator, might not permit the patient to complete the trial or sign the informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00932724

Locations

Germany
Klinikum der Johann Wolfgang-Universität Frankfurt	Not yet recruiting
Frankfurt a.M., Germany, 60590
Contact: Lothar Bergmann, Prof., MD +496963015124 l.bergmann@em.uni-frankfurt.de
Principal Investigator: Lothar Bergmann, Prof., MD
Sub-Investigator: Shabnam Shaid, MD
Sub-Investigator: Luise Maute, MD
Universitätsklinik Dresden	Recruiting
Dresden, Germany, 01307
Contact: Gunnar Folprecht, MD +49351449210629 Gunnar.Folprecht@uniklinikum-dresden.de
Principal Investigator: Gunnar Folprecht, MD
Sub-Investigator: Anke Frömmel, MD
Sub-Investigator: Jan Stöhlmacher, MD
Sub-Investigator: Eray Goekkurt, MD
Sub-Investigator: Karolin Trautmann-Grill, MD
Sub-Investigator: Heinrich Günther, MD
Klinikum Lüdenscheid	Recruiting
Luedenscheid, Germany, 58515
Contact: Gerhard Heil, Prof., MD +492351463539 gerhard.heil@klinikum-luedenscheid.de
Principal Investigator: Gerhard Heil, Prof., MD
Sub-Investigator: Sabine Drygas, MD
Prosper-Hospital	Not yet recruiting
Recklinghausen, Germany, 45657
Contact: Thomas Höhler, Prof., MD +492361542696 thomas.hoehler@prosper-hospital.de
Principal Investigator: Thomas Höhler, Prof., MD
Sub-Investigator: Claudia Baller
Westdeutsches Tumorzentrum - Universitätsklinikum Essen	Recruiting
Essen, Germany, 45147
Contact: Max Scheulen, Prof., MD +492017233790 mas.scheulen@uk-essen.de
Principal Investigator: Max Scheulen, Prof., MD
Sub-Investigator: Bahar Nokay
Sub-Investigator: Heike Richly, MD
Marienhospital Herne	Not yet recruiting
Herne, Germany, 44625
Contact: Dirk Strumberg, PD, MD +4923234991641 dirk.strumberg@marienhospital-herne.de
Principal Investigator: Dirk Strumberg, PD, MD
Sub-Investigator: Gerhard Kurt Kummer, MD
Sub-Investigator: Beate Schultheis, MD
Klinikum Dortmund GmbH	Recruiting
Dortmund, Germany, 44137
Contact: Sabine Bäumer, MD +49 231 953 20780 sabine.baeumer@klinikumdo.de
Principal Investigator: Sabine Bäumer, MD
Sub-Investigator: Michael Heike, Prof., MD
Sub-Investigator: Yvonne Prophet
Sub-Investigator: Peter Boris Czyborra, MD
MVZ Onkologische Schwerpunktpraxis	Not yet recruiting
Frankfurt, Germany, 60596
Contact: Hans-Jörg Cordes, MD +49650073200 info@ifs-frankfurt.de
Principal Investigator: Hans-Jörg Cordes, MD
Sub-Investigator: Regina Claude, MD
Sub-Investigator: Hermann, MD
Martin-Luther Universität Halle	Recruiting
Halle/Saale, Germany, 06120
Contact: Dirk Arnold, MD +49 345 5572849 dirk.arnold@medizin.uni-halle.de
Principal Investigator: Dirk Arnold, MD
Sub-Investigator: Jörn Rüssel
Sub-Investigator: Christoph Sippel
Onkologische Schwerpunktpraxis	Recruiting
Hamburg, Germany, 20249
Contact: Susanne Hegewisch-Becker, Prof., MD +49404602001 hegewisch@t-online.de
Principal Investigator: Susanna Hegewisch-Becker, Prof., MD
Sub-Investigator: Michael Begemann, MD
Sub-Investigator: Thorsten Dierlamm, MD
Onkologische Schwerpunktpraxis	Recruiting
Hildesheim, Germany, 31135
Contact: Werner Freier, MD +4951219129140 dr.freier@onkologie-hildesheim.de
Principal Investigator: Werner Freier, MD
Sub-Investigator: Bernd Sievers, MD
Gesundheitszentrum St. Marien GmbH am Klinikum St. Marien	Recruiting
Amberg, Germany, 922224
Contact: Ludwig Fischer v. Weikersthal, MD +499621381637 weikersthal.ludwig@klinikum-amberg.de
Principal Investigator: Ludwig Fischer v. Weikersthal, MD
Johanness-Gutenberg Universität Mainz	Not yet recruiting
Mainz, Germany, 55101
Contact: Markus Möhler, PD, MD +496131176863 moehler@mail.uni-mainz.de
Principal Investigator: Markus Möhler, PD, MD
Sub-Investigator: Carl Christoph Schimanski, PD, MD
Sub-Investigator: Andreas Teufel, MD
Sub-Investigator: Frank Staib, MD
Klinikum Esslingen	Recruiting
Esslingen, Germany, 7370
Contact: Michael Geißler, Prof., MD +49711310382450 m.geissler@klinikum-es.de
Principal Investigator: Michael Geißler, Prof., MD
Sub-Investigator: Caroline Hörner, MD
Sub-Investigator: Heike Karin Mönnich, MD
Universitätsklinikum Ulm	Not yet recruiting
Ulm, Germany, 89081
Contact: Gätz v. Wichert, PD, MD +497315004450508 goetz.wichert@uniklinikum-ulm.de
Principal Investigator: Götz v. Wichert, PD, MD
Sub-Investigator: Johann Ahn, MD
Sub-Investigator: Jochen Klaus, MD
Sub-Investigator: Sven Walter, MD
Universitätsklinkum Heidelberg - Nationales Centrum f. Tumorerkrankungen	Not yet recruiting
Heidelberg, Germany, 69120
Contact: Thomas Hermann, Prof., MD +4962215638725 Thomas.Hermann@med.uni-heidelberg.de
Principal Investigator: Thomas Hermann, Prof., MD
Sub-Investigator: Leonidas Apostolidis, MD
Sub-Investigator: Christian Suppan, MD
Sub-Investigator: Guy Ungerechts, MD
Praxis für Hämatologie und internistische Onkologie	Recruiting
München, Germany, 80638
Contact: Oliver J. Stötzer, MD +498913958588 ojstoetzer@aol.com
Principal Investigator: Oliver J. Stötzer, MD
Praxis für Hämatologie und internistische Onkologie	Recruiting
Kronach, Germany, 96317
Contact: Martina Stauch, MD +49 9261 6248 ext 0 praxisdrstauch@t-online.de
Principal Investigator: Martina Stauch, MD
Klinikum Bayreuth	Not yet recruiting
Bayreuth, Germany, 95445
Contact: Christoph Stoll, MD +499214006310 christoph.stoll@klinkum-bayreuth.de
Principal Investigator: Christoph Stoll, MD
Sub-Investigator: Stefan Klein, MD
Sub-Investigator: Daniela B Heidenreich, MD
Onkologische Schwerpunktpraxis	Recruiting
Hof, Germany, 95028
Contact: Hanns D Harich, MD +499281540060 praxis.harich.kasper@web.de
Principal Investigator: Hanns D Harich, MD
Sub-Investigator: Christian Kasper, MD
Klinikum Nordoberpfalz AG	Not yet recruiting
Weiden Oberpfalz, Germany, 92637
Contact: Frank Kullmann, Prof., MD +499613030 frank.kullmann@kliniken-nordoberpfalz.ag
Principal Investigator: Frank Kullmann, Prof., MD
Sub-Investigator: Swetlana Zimmermann

Sponsors and Collaborators

Cytavis Biopharma GmbH

ClinAssess GmbH

Medizinische Univ. Insbruck - Koordinierungszentrum für Klinische Studien (KKS)

Charité Universitätsmedizin Berlin - Institut für Medizinische Immunologie

Investigators

Principal Investigator:	Heinz Zwierzina, MD	University Hospital Innsbruck, Austria
Principal Investigator:	Lothar Bergmann, MD	University Hospital Frankfurt, Germany

Responsible Party:	Cytavis Biopharma GmbH ( Prof. Hans Lentzen, PhD )
Study ID Numbers:	CY503C2, EudraCT no. 2008-005536-32
Study First Received:	June 25, 2009
Last Updated:	September 8, 2009
ClinicalTrials.gov Identifier:	NCT00932724 History of Changes
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices; Austria: Agency for Health and Food Safety