Metastatic Colorectal CancerPhase 2CY503C2NCT00932724
CY-503 for the Treatment of Chemotherapy-refractory Metastatic Colorectal Cancer
A Phase 2 study testing CY-503 in people with Metastatic Colorectal Cancer, run by Cytavis Biopharma GmbH at 33 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- CY-503
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 77 participants
- Where
- 33 sitesin 2 countries
- Study dates
- Jul 2009to Aug 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
33 sites in 2 countries.
33 sites in 2 countries
Germany29 sites
Klinikum Altenburger Land GmbH
Altenburg, 04600
Gesundheitszentrum St. Marien GmbH am Klinikum St. Marien
Amberg, 922224
Studienzentrum f. Hämatologie, Onkologie u. Diabetologie
Aschaffenburg, 63739
Klinikum Bayreuth
Bayreuth, 95445
Praxis Onkologie
Cologne, 51103
Klinikum Dortmund GmbH
Dortmund, 44137
Universitätsklinik Dresden
Dresden, 01307
Westdeutsches Tumorzentrum - Universitätsklinikum Essen
Essen, 45147
Klinikum Esslingen
Esslingen am Neckar, 7370
MVZ Onkologische Schwerpunktpraxis
Frankfurt, 60596
Klinikum der Johann Wolfgang-Universität Frankfurt
Frankfurt a.M., 60590
Martin-Luther Universität Halle
Halle, 06120
Onkologische Schwerpunktpraxis
Hamburg, 20249
Universitätsklinkum Heidelberg - Nationales Centrum f. Tumorerkrankungen
Heidelberg, 69120
Marienhospital Herne
Herne, 44625
Onkologische Schwerpunktpraxis
Hildesheim, 31135
Onkologische Schwerpunktpraxis
Hof, 95028
Praxis für Hämatologie und internistische Onkologie
Kronach, 96317
Klinikum Lüdenscheid
Lüdenscheid, 58515
Klinikum der Stadt Ludwigshafen
Ludwigshafen, 67063
Klinikum Magdeburg gGmbH
Magdeburg, 39130
Johanness-Gutenberg Universität Mainz
Mainz, 55101
Praxis für Hämatologie und internistische Onkologie
München, 80638
Gemeinschaftspraxis f. Hämatologie u. Onkologie
Münster, 48149
Studienzentrum Onkologie Ravensburg
Ravensburg, 88212
Prosper-Hospital
Recklinghausen, 45657
Onkologische Schwerpunktpraxis, Hämatologie und Onkologie
Trier, 54292
Universitätsklinikum Ulm
Ulm, 89081
Klinikum Nordoberpfalz AG
Weiden Oberpfalz, 92637
Austria4 sites
Bezirkskrankenhaus Hall
Hall in Tirol, 6060
Medizinische Universität Innsbruck
Innsbruck, 6020
Bezirkskrankenhaus Kufstein
Kufstein, 6330
St. Vinzenz Krankenhaus Zams
Zams, 6511
About this study
Official title: Phase II Double-blind Placebo-controlled Trial of CY503 in Patients With Chemotherapy-refractory Metastatic Colorectal Cancer
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.
Read the 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.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- CY-503, Placebo
- Keywords
- Metastatic, Colorectal, Cancer, refractory, Phase II, randomised, double-blind, controlled, multicenter, CY-503, Cytavis
- Medical subject headings
- Colorectal Neoplasms, Neoplasm Metastasis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CY-503Drug
Ampoules with 1 ml 350 ng CY-503 solution for s.c. injection twice weekly. One cycle is defined as 4 consecutive weeks
PlaceboDrug
Ampoules with 1 ml placebo solution for s.c. injection twice weekly. One cycle is defined as 4 consecutive weeks
| Study group | Role | What they receive |
|---|---|---|
| CY-503 | Experimental | Not described Receives: Drug: CY-503 |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor assessment by using CT scans and/or MRIs
Measured: every 8 weeks (each 2 cycles)
Secondary outcomes (3)
Assessment of Adverse Events
Measured: every 4 weeks (every cycle)
Assessment of quality of life using a standardized questionaire
Measured: every 4 weeks (every cycle)
Assessment of survival by "physical exam"
Measured: every 4 weeks (every cycle) / every 3 months during follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2009 (estimated)
- Study startJul 2009
- Primary completionAug 2012
- Study completionAug 2012
Why it stopped: The sponsor declared the early termination of the study due to poor recruitment of patients.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cytavis Biopharma GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ClinAssess GmbH, Medical University Innsbruck, Charite University, Berlin, Germany
- Investigators
- Heinz Zwierzina, MD, Principal investigator, University Hospital Innsbruck, AustriaLothar Bergmann, MD, Principal investigator, University Hospital, Frankfurt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00932724
- Sponsor's protocol ID
- CY503C2
- Other IDs
- EudraCT no. 2008-005536-32
- Acronym
- CY503C2
- Status last verified
- Jun 2011
- First submitted
- 25 Jun 2009
- Last updated
- 10 Jul 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Double-blind Placebo-controlled Trial of CY503 in Patients With Chemotherapy-refractory Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT00932724
- Acronym / sponsor ID
- CY503C2 / CY503C2
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Metastatic, Colorectal, Cancer, refractory, Phase II, randomised, double-blind, controlled
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The sponsor declared the early termination of the study due to poor recruitment of patients.
- Enrolment
- 77 participants (actual)
- Lead sponsor
- Cytavis Biopharma GmbHIndustry (pharma, biotech, devices)
- Collaborators
- ClinAssess GmbH, Medical University Innsbruck, Charite University, Berlin, Germany
- Study start
- Jul 2009
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 3 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CY-503 | Experimental | Drug: CY-503 |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (14 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CY-503Ampoules with 1 ml 350 ng CY-503 solution for s.c. injection twice weekly. One cycle is defined as 4 consecutive weeks | Drug | CY-503 |
| PlaceboAmpoules with 1 ml placebo solution for s.c. injection twice weekly. One cycle is defined as 4 consecutive weeks | Drug | Placebo |
Primary outcome
Tumor assessment by using CT scans and/or MRIs
Time frame: every 8 weeks (each 2 cycles)
3 secondary outcomes
Assessment of Adverse Events
Time frame: every 4 weeks (every cycle)
Assessment of quality of life using a standardized questionaire
Time frame: every 4 weeks (every cycle)
Assessment of survival by "physical exam"
Time frame: every 4 weeks (every cycle) / every 3 months during follow-up
Results and safety
The study was stopped early (reason given: The sponsor declared the early termination of the study due to poor recruitment of patients.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2013.
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CRC
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heinz Zwierzina, MD principal investigator
University Hospital Innsbruck, Austria
Lothar Bergmann, MD principal investigator
University Hospital, Frankfurt, Germany
33 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CY-503 in people with Metastatic Colorectal Cancer, run by Cytavis Biopharma GmbH at 33 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in Germany, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The sponsor declared the early termination of the study due to poor recruitment of patients.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumor assessment by using CT scans and/or MRIs (time frame: every 8 weeks (each 2 cycles)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2013.