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

Metastatic Colorectal Cancer Clinical Trial

— CY503C2  

Official title:

Phase II Double-blind Placebo-controlled Trial of CY503 in Patients With Chemotherapy-refractory Metastatic Colorectal Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00932724
• Other study ID #: CY503C2
• Secondary ID: EudraCT no. 2008
• Status: Terminated
• Phase: Phase 2
• First received: June 25, 2009
• Last updated: July 9, 2013
• Start date: July 2009
• Est. completion date: August 2012

Study information

• Verified date: June 2011
• Source: Cytavis Biopharma GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesAustria: Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 77
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Age = 18 years

• Patients are eligible with diagnosis of measurable metastatic colorectal carcinoma and radiologic documentation of disease progression during or with 3 months after termination of standard chemotherapy (fluoropyrimidine-based therapy with oxaliplatin and irinotecan). Patients who had to interrupt the 1st or 1nd line therapy due to intolerance or who were refractory or intolerant to the standard treatment regimens are eligible, too. Bevacizumab can, but does not need to be administered at discretion of treating physician. Patients with K-RAS wild-type can be treated with cetuximab or panitumumab before they enter the study.

• No chemotherapy within 4 weeks before treatment start

• No residual significant toxicity (greater than NCI grade 1), in case of peripheral neuropathy: no symptoms of peripheral neuropathy of NCI CTC grade 4 within 4 weeks before treatment start.

• No previous treatment with experimental therapies after standard therapies is allowed.

• 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 = 2.0 mg/dL (40 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) = 5 × 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 = 2.0 mg/dL (180 µmol/L)or creatinine clearance >= 50 ml/min. , 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 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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

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
Ampoules with 1 ml placebo solution for s.c. injection twice weekly. One cycle is defined as 4 consecutive weeks

Locations

Country	Name	City	State
Austria	Bezirkskrankenhaus Hall	Hall in Tirol
Austria	Medizinische Universität Innsbruck	Innsbruck
Austria	Bezirkskrankenhaus Kufstein	Kufstein
Austria	St. Vinzenz Krankenhaus Zams	Zams
Germany	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	MVZ Onkologische Schwerpunktpraxis	Frankfurt
Germany	Klinikum der Johann Wolfgang-Universität Frankfurt	Frankfurt a.M.
Germany	Martin-Luther Universität Halle	Halle/Saale
Germany	Onkologische Schwerpunktpraxis	Hamburg
Germany	Universitätsklinkum Heidelberg - Nationales Centrum f. Tumorerkrankungen	Heidelberg
Germany	Marienhospital Herne	Herne
Germany	Onkologische Schwerpunktpraxis	Hildesheim
Germany	Onkologische Schwerpunktpraxis	Hof
Germany	Praxis Onkologie	Köln
Germany	Praxis für Hämatologie und internistische Onkologie	Kronach
Germany	Klinikum der Stadt Ludwigshafen	Ludwigshafen
Germany	Klinikum Lüdenscheid	Luedenscheid
Germany	Klinikum Magdeburg gGmbH	Magdeburg
Germany	Johanness-Gutenberg Universität Mainz	Mainz
Germany	Praxis für Hämatologie und internistische Onkologie	München
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

Sponsors (4)

Lead Sponsor	Collaborator
Cytavis Biopharma GmbH	Charite University, Berlin, Germany, ClinAssess GmbH, Medical University Innsbruck

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor assessment by using CT scans and/or MRIs		every 8 weeks (each 2 cycles)	No
Secondary	Assessment of Adverse Events		every 4 weeks (every cycle)	Yes
Secondary	Assessment of quality of life using a standardized questionaire		every 4 weeks (every cycle)	No
Secondary	Assessment of survival by "physical exam"		every 4 weeks (every cycle) / every 3 months during follow-up	No