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

Phase 2
Terminated
Conditions
Metastatic Colorectal Cancer
Interventions
Drug: Placebo
Registration Number
NCT00932724
Lead Sponsor
Cytavis Biopharma GmbH
Brief Summary

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.

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
77
Inclusion Criteria

Not provided

Exclusion Criteria
  • Evidence of any other malignant disease (with the exception of tumors 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 and/or monoclonal antibodies 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 prednisone-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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CY-503CY-503-
PlaceboPlacebo-
Primary Outcome Measures
NameTimeMethod
Tumor assessment by using CT scans and/or MRIsevery 8 weeks (each 2 cycles)
Secondary Outcome Measures
NameTimeMethod
Assessment of Adverse Eventsevery 4 weeks (every cycle)
Assessment of quality of life using a standardized questionaireevery 4 weeks (every cycle)
Assessment of survival by "physical exam"every 4 weeks (every cycle) / every 3 months during follow-up

Trial Locations

Locations (30)

Bezirkskrankenhaus Hall

🇦🇹

Hall in Tirol, Austria

St. Vinzenz Krankenhaus Zams

🇦🇹

Zams, Austria

Onkologische Schwerpunktpraxis

🇩🇪

Hof, Germany

Bezirkskrankenhaus Kufstein

🇦🇹

Kufstein, Austria

Klinikum Altenburger Land GmbH

🇩🇪

Altenburg, Germany

Gesundheitszentrum St. Marien GmbH am Klinikum St. Marien

🇩🇪

Amberg, Germany

Studienzentrum f. Hämatologie, Onkologie u. Diabetologie

🇩🇪

Aschaffenburg, Germany

Klinikum Bayreuth

🇩🇪

Bayreuth, Germany

Klinikum Dortmund GmbH

🇩🇪

Dortmund, Germany

Universitätsklinik Dresden

🇩🇪

Dresden, Germany

Westdeutsches Tumorzentrum - Universitätsklinikum Essen

🇩🇪

Essen, Germany

Klinikum Esslingen

🇩🇪

Esslingen, Germany

Klinikum der Johann Wolfgang-Universität Frankfurt

🇩🇪

Frankfurt a.M., Germany

MVZ Onkologische Schwerpunktpraxis

🇩🇪

Frankfurt, Germany

Martin-Luther Universität Halle

🇩🇪

Halle/Saale, Germany

Universitätsklinkum Heidelberg - Nationales Centrum f. Tumorerkrankungen

🇩🇪

Heidelberg, Germany

Marienhospital Herne

🇩🇪

Herne, Germany

Praxis Onkologie

🇩🇪

Köln, Germany

Praxis für Hämatologie und internistische Onkologie

🇩🇪

München, Germany

Klinikum der Stadt Ludwigshafen

🇩🇪

Ludwigshafen, Germany

Klinikum Lüdenscheid

🇩🇪

Luedenscheid, Germany

Klinikum Magdeburg gGmbH

🇩🇪

Magdeburg, Germany

Johanness-Gutenberg Universität Mainz

🇩🇪

Mainz, Germany

Gemeinschaftspraxis f. Hämatologie u. Onkologie

🇩🇪

Münster, Germany

Studienzentrum Onkologie Ravensburg

🇩🇪

Ravensburg, Germany

Prosper-Hospital

🇩🇪

Recklinghausen, Germany

Onkologische Schwerpunktpraxis, Hämatologie und Onkologie

🇩🇪

Trier, Germany

Universitätsklinikum Ulm

🇩🇪

Ulm, Germany

Klinikum Nordoberpfalz AG

🇩🇪

Weiden Oberpfalz, Germany

Medizinische Universität Innsbruck

🇦🇹

Innsbruck, Austria

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