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

Sponsor

Cytavis Biopharma GmbH (Industry)

Overall Status

Terminated

CT.gov ID

NCT00932724

Collaborator

ClinAssess GmbH (Industry), Medical University Innsbruck (Other), Charite University, Berlin, Germany (Other)

Enrollment

Locations

Arms

Duration (Months)

2.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: CY-503 Drug: Placebo	Phase 2

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

Study Type:

Interventional

Actual Enrollment :

77 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2009

Actual Primary Completion Date :

Aug 1, 2012

Actual Study Completion Date :

Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Tumor assessment by using CT scans and/or MRIs [every 8 weeks (each 2 cycles)]

Secondary Outcome Measures

Assessment of Adverse Events [every 4 weeks (every cycle)]
Assessment of quality of life using a standardized questionaire [every 4 weeks (every cycle)]
Assessment of survival by "physical exam" [every 4 weeks (every cycle) / every 3 months during follow-up]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country	Postal Code
1	Bezirkskrankenhaus Hall	Hall in Tirol	Austria	6060
2	Medizinische Universität Innsbruck	Innsbruck	Austria	6020
3	Bezirkskrankenhaus Kufstein	Kufstein	Austria	6330
4	St. Vinzenz Krankenhaus Zams	Zams	Austria	6511
5	Klinikum Altenburger Land GmbH	Altenburg	Germany	04600
6	Gesundheitszentrum St. Marien GmbH am Klinikum St. Marien	Amberg	Germany	922224
7	Studienzentrum f. Hämatologie, Onkologie u. Diabetologie	Aschaffenburg	Germany	63739
8	Klinikum Bayreuth	Bayreuth	Germany	95445
9	Klinikum Dortmund GmbH	Dortmund	Germany	44137
10	Universitätsklinik Dresden	Dresden	Germany	01307
11	Westdeutsches Tumorzentrum - Universitätsklinikum Essen	Essen	Germany	45147
12	Klinikum Esslingen	Esslingen	Germany	7370
13	Klinikum der Johann Wolfgang-Universität Frankfurt	Frankfurt a.M.	Germany	60590
14	MVZ Onkologische Schwerpunktpraxis	Frankfurt	Germany	60596
15	Martin-Luther Universität Halle	Halle/Saale	Germany	06120
16	Onkologische Schwerpunktpraxis	Hamburg	Germany	20249
17	Universitätsklinkum Heidelberg - Nationales Centrum f. Tumorerkrankungen	Heidelberg	Germany	69120
18	Marienhospital Herne	Herne	Germany	44625
19	Onkologische Schwerpunktpraxis	Hildesheim	Germany	31135
20	Onkologische Schwerpunktpraxis	Hof	Germany	95028
21	Praxis für Hämatologie und internistische Onkologie	Kronach	Germany	96317
22	Praxis Onkologie	Köln	Germany	51103
23	Klinikum der Stadt Ludwigshafen	Ludwigshafen	Germany	67063
24	Klinikum Lüdenscheid	Luedenscheid	Germany	58515
25	Klinikum Magdeburg gGmbH	Magdeburg	Germany	39130
26	Johanness-Gutenberg Universität Mainz	Mainz	Germany	55101
27	Praxis für Hämatologie und internistische Onkologie	München	Germany	80638
28	Gemeinschaftspraxis f. Hämatologie u. Onkologie	Münster	Germany	48149
29	Studienzentrum Onkologie Ravensburg	Ravensburg	Germany	88212
30	Prosper-Hospital	Recklinghausen	Germany	45657
31	Onkologische Schwerpunktpraxis, Hämatologie und Onkologie	Trier	Germany	54292
32	Universitätsklinikum Ulm	Ulm	Germany	89081
33	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