Patients suffering from advanced, recurrent or metastatic gastrointestinal adenocarcinoma. MedDRA version: 18.1 Level: HLGT Classification code 10017991 Term: Gastrointestinal neoplasms malignant and unspecified System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: MSC_apceth_101
Pharmaceutical Form: Infusion
Trade Name: Cymeven i.v.
Product Name: Cymeven i.v.
Pharmaceutical Form: Powder for solution for infusion
Sponsors
apceth GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with advanced or recurrent or metastatic gastrointestinal adenocarcinoma. Target indications: cancer of the esophagus (cTNM: T3NxMx or T4NxMx); pancreatic (cTNM: T3NxMx); or gastric cancer (cTNM: T3NxMx or T4NxMx); or intrahepatic cholangiocellular carcinoma (cTNM: T3NxMx or T4NxMx); or metastases due to colorectal cancer (cTNM: TxNxM1). The TNM classification should not be older than 4 months. 2. Premature or scheduled termination of standard therapy (including possible preoperative therapy) due to intolerability / progress / inefficacy or no acceptance by the patient if re-lapses/metastases are measurable by means of imaging techniques. No relapse and no metastases should exceed 5 cm in its maximal diameter. 3. In case of metastases due to colorectal cancer: • Metastases are unresectable • The total volume of the liver metastases does not exceed 30 % of the total liver volume • In addition to liver metastases lung metastases (as assessed by a radiologists with a minimum diameter of at least 0.5 cm) are allowed, however, not more than 10 with the largest one not exceeding 2 cm in diameter • Lymph node metastases are permitted • Brain metastases: As long as only one organ is affected by extra-cranial metastases due to colorectal cancer no radio-logical investigation for brain metastases is needed if there are no signs or symptoms suspicious for brain metastases. In case of liver and lung metastases the patient has to be excluded unless a cranial image verifies absence of brain metastases 4. Patients who have donated bone marrow for the production of MSC_apceth_101 based on a separate approved protocol. MSC_apceth_101 must have been released for the (autologous) use in the same patient. 5. Progressive disease as clinically assessed by the investigator. In addtion: A.1 Adequate organ function: a. Hb > 9.0 g/dl b. WBC > 3,000 cells/µl c. Neutrophils >500 /µl c. Platelets > 100,000 cells/µl d. ALT/AST = 3 ULN (or = 5 ULN in case of intrahepatic cholangiocellular carcinoma) e. total bilirubin = 1.5 ULN (or = 2 ULN in case of intrahepatic cholangiocellular carci-noma) f. Creatinine = 2.0 mg/dl g.Creatinine clearance = 50 ml/min A.2 Anticipated minimal life expectancy of at least 6 months A.3 Men and women of reproductive potential must agree to follow accepted contraception methods during treatment and for 3 months after completion of treatment. Medically acceptable methods of birth control are methods with a low failure rate of less than 1% per year; e.g. hormonal contraceptives for at least the 7 days before trial enrolment or an intrauterine device, or double barrier method (male or female condom or diaphragm, in com-bination with a spermicidal gel). All women, including those with tubal ligation, are considered to be of childbearing potential unless they have been postmenopausal for at least 2 years. Hysterectomized women are considered surgically sterile and are not required to use any contraception. Males should not participate in a sperm donation program. A.4 Ability of patient to understand character and individual consequences of clinical trial A.5 Age = 18 years A.6 Written informed consent must be available before any study specific procedure is performed Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 14 F.1.3 Elderly (>=65 years) yes F.1.3.1 Numbe
Exclusion criteria
Exclusion criteria: 1. Patients with severe heart diseases (NYHA stage three and four; unstable angina pectoris, or myocardial infarction during the last 8 weeks before Visit 1 (Baseline)) 2. Clinical significant ischemic disease during the last 4 weeks before Visit 1 (Baseline) 3. Severe lung disease (COPD Grade III, Asthma bronchiale Grade IV, lung fibrosis) 4. General condition worse than ECOG 2 5. Symptomatic peritoneal carcinomatosis (e.g. by the presence of ascites) 6. Symptomatic pleural or pericardial effusion 7. Serious uncontrolled acute infections less than 3 weeks before Visit 1 (Baseline) 8. Patients with HCV infection as defined by anti-HCV pos and HCV RNA pos and / or HBV in-fection as defined by anti-Hbc pos and/ or HBV DNA pos 9. Patients with HIV infection as minimally demonstrated by HIV RNA 10. Immunodeficiencies or systemic autoimmune diseases (e.g. M. Crohn, Colitis ulcerosa) or known malformations of the gastrointestinal tract 11. Active infection with HSV (by IgM pos) 12. Second carcinoma in addition to the underlying carcinoma unless the second carcinoma was curatively and successfully resected more than 5 years ago before Visit 1 (Baseline) (exception: basal cell carcinoma, precancerous conditions) 13. Use of any immunomodulators 14. Need for chemotherapy or radiotherapy or cytokine treatment (e.g. interferons, G-CSF or GM-CSF) in the time interval 2 weeks before infusion of MSC_apceth_101 or anticipation of chemo- or radiotherapy during treatment with MSC_apceth_101 and GCV until 2 days after the last administration of GCV 15. Known dependency on alcohol or other drugs 16. Patients requiring corticoids in doses above the Cushing threshold 17. Known liver fibrosis or liver cirrhosis 18. Any concomitant severe disease which could compromise the objectives of this study in the judgment of the investigator 19. Female patient who is pregnant or breast feeding 20. Participation in another clinical trial or observation period, respectively, during the last 4 weeks prior to the first MSC_apceth_101 dose 21. Any surgery in the last four weeks before the administration of MSC_apceth_101 22. History of hypersensitivity to the investigational product or to Ganciclovir, Valganciclovir, Aciclovir or Valaciclovir 23. Any contraindication to Ganciclovir (see package insert) or the need for the following drugs interacting with Ganciclovir: Probenecid; combination of Imipenem-Cilastatin; Dapson, Pen-tamidin; Flucystosin; Vincristin, Vinblastin, Adriamycin, Amphotericin B; combination of Tri-methoprim and Sulfonamides, Nucleosideanaloga or Hydroxy-urea. This is confined to the time period 14 days prior to Ganciclovir and up to 7 days after termination of Ganciclovir treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of MSC_apceth_101;Secondary Objective: • Efficacy based on RECIST criteria and on tumor/serum markers • Quality of life ;Primary end point(s): The primary endpoints, safety and tolerability of MSC_apceth_101 will be assessed by: • Adverse event listings and tables based on MedDRA terms, severity grade, relationship to both study medications and CTC-AE grades • Listings for laboratory values. Additionally, descriptive statistics will be provided for laboratory parameters. • For all other safety data, listings and descriptive statistics (for continuous variables) or frequency tables (for categorical variables) will be provided. ;Timepoint(s) of evaluation of this end point: 2 months after first treatment with MSC_apceth_101. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints will be imaging results obtained by CT or MRT (classified by RECIST criteria), laboratory data for tumor and serum markers, the overall survival of patients and time to tumor progression. ;Timepoint(s) of evaluation of this end point: 2 months after first treatment with MSC_apceth_101. | — |
Countries
Germany
Contacts
Public ContactClinical Trial Manager
apceth GmbH & Co. KG
Outcome results
None listed