CY-503 for the Treatment of Chemotherapy-refractory Metastatic Colorectal Cancer (CY503C2)

This study has been terminated.
(The sponsor declared the early termination of the study due to poor recruitment of patients.)
Sponsor:
Collaborators:
ClinAssess GmbH
Medical University Innsbruck
Charite University, Berlin, Germany
Information provided by:
Cytavis Biopharma GmbH
ClinicalTrials.gov Identifier:
NCT00932724
First received: June 25, 2009
Last updated: July 9, 2013
Last verified: June 2011
  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 2

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

Resource links provided by NLM:


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 exam" [ Time Frame: every 4 weeks (every cycle) / every 3 months during follow-up ] [ Designated as safety issue: No ]

Enrollment: 77
Study Start Date: July 2009
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CY-503 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 Comparator: Placebo 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Austria
Bezirkskrankenhaus Hall
Hall in Tirol, Austria, 6060
Medizinische Universität Innsbruck
Innsbruck, Austria, 6020
Bezirkskrankenhaus Kufstein
Kufstein, Austria, 6330
St. Vinzenz Krankenhaus Zams
Zams, Austria, 6511
Germany
Klinikum Altenburger Land GmbH
Altenburg, Germany, 04600
Gesundheitszentrum St. Marien GmbH am Klinikum St. Marien
Amberg, Germany, 922224
Studienzentrum f. Hämatologie, Onkologie u. Diabetologie
Aschaffenburg, Germany, 63739
Klinikum Bayreuth
Bayreuth, Germany, 95445
Klinikum Dortmund GmbH
Dortmund, Germany, 44137
Universitätsklinik Dresden
Dresden, Germany, 01307
Westdeutsches Tumorzentrum - Universitätsklinikum Essen
Essen, Germany, 45147
Klinikum Esslingen
Esslingen, Germany, 7370
MVZ Onkologische Schwerpunktpraxis
Frankfurt, Germany, 60596
Klinikum der Johann Wolfgang-Universität Frankfurt
Frankfurt a.M., Germany, 60590
Martin-Luther Universität Halle
Halle/Saale, Germany, 06120
Onkologische Schwerpunktpraxis
Hamburg, Germany, 20249
Universitätsklinkum Heidelberg - Nationales Centrum f. Tumorerkrankungen
Heidelberg, Germany, 69120
Marienhospital Herne
Herne, Germany, 44625
Onkologische Schwerpunktpraxis
Hildesheim, Germany, 31135
Onkologische Schwerpunktpraxis
Hof, Germany, 95028
Praxis für Hämatologie und internistische Onkologie
Kronach, Germany, 96317
Praxis Onkologie
Köln, Germany, 51103
Klinikum der Stadt Ludwigshafen
Ludwigshafen, Germany, 67063
Klinikum Lüdenscheid
Luedenscheid, Germany, 58515
Klinikum Magdeburg gGmbH
Magdeburg, Germany, 39130
Johanness-Gutenberg Universität Mainz
Mainz, Germany, 55101
Praxis für Hämatologie und internistische Onkologie
München, Germany, 80638
Gemeinschaftspraxis f. Hämatologie u. Onkologie
Münster, Germany, 48149
Studienzentrum Onkologie Ravensburg
Ravensburg, Germany, 88212
Prosper-Hospital
Recklinghausen, Germany, 45657
Onkologische Schwerpunktpraxis, Hämatologie und Onkologie
Trier, Germany, 54292
Universitätsklinikum Ulm
Ulm, Germany, 89081
Klinikum Nordoberpfalz AG
Weiden Oberpfalz, Germany, 92637
Sponsors and Collaborators
Cytavis Biopharma GmbH
ClinAssess GmbH
Medical University Innsbruck
Charite University, Berlin, Germany
Investigators
Principal Investigator: Heinz Zwierzina, MD University Hospital Innsbruck, Austria
Principal Investigator: Lothar Bergmann, MD University Hospital Frankfurt, Germany
  More Information

No publications provided

Responsible Party: Prof. Hans Lentzen, PhD, Cytavis Biopharma GmbH
ClinicalTrials.gov Identifier: NCT00932724     History of Changes
Other Study ID Numbers: CY503C2, EudraCT no. 2008-005536-32
Study First Received: June 25, 2009
Last Updated: July 9, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Austria: Agency for Health and Food Safety

Keywords provided by Cytavis Biopharma GmbH:
Metastatic
Colorectal
Cancer
refractory
Phase II
randomised
double-blind
controlled
multicenter
CY-503
Cytavis

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on July 08, 2014