A Phase I/II dose-escalation trial investigating the oncolytic virus TMV-018 in combination with a chemotherapy precursor (5-Fluorocytosine) or an immunotherapeutic agent (anti-PD-1 therapy) in patients with tumors of the gastrointestinal tract in terms of safety, clinical activity as well as pharmacokinetics and pharmacodynamics.
- Conditions
- Patients with histologically confirmed diagnosis of colorectal carcinoma (left-sided or rectal), esophageal carcinoma, or gastric cancer.MedDRA version: 21.1Level: LLTClassification code 10062240Term: Tumor vaccine therapySystem Organ Class: 100000004865Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003550-88-DE
- Lead Sponsor
- Themis Bioscience GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 39
1. Signed informed consent form must be obtained prior to any research procedures.
2. At least 18 years of age on the day of signing the informed consent.
3. Histologically confirmed diagnosis of tumors of the gastrointestinal tract (colo¬rectal cancer (left side or rectal), gastric cancer, esophageal cancer being accessible for endoscope guided injection (without intake of oral laxatives) and sub¬sequent repetitive biopsy taking.
4. Before enrolment (i.e., at least 4 weeks before study treatment): Prior chemotherapy, targeted therapy (e.g., bevacizumab), radiotherapy, to treat cancer or major surgery have to be stopped at least 4 weeks prior to enrolment.
5. Eastern Cooperative Oncology Group (ECOG) performance status = 2 and life expectancy = 3 months as assessed during screening period.
6. All female participants of childbearing potential, defined as all woman physiologically capable of becoming pregnant, must have a negative pregnancy test at screening.
7. Willingness not to become pregnant or to father a child during study participation by practicing reliable methods of contraception.
8. In case of gastric or esophageal cancer, subjects must have under¬gone at least one line of anti-tumoral therapy. Patients with colorectal cancer (left side or rectal) must have undergone at least two lines of anti-tumoral therapy.
9. Adequate organ function (hematological, renal, hepatic, coagulation within 2 weeks prior to enrollment defined as follows:
• ANC = 1500/mm3 (1.5 x 109/L)
•Platelet count = 100 000/mm3 (100 x 109/L)
•Hemoglobin = 9 g/dL (90 g/L)
•Serum creatinin = 1.5 x ULN or creatinine clearance = 60 mL/min for subjects with creatinine levels > 1.5 x ULN
•Serum total bilirubin = 1.5 x ULN
•AST = 2.5 x ULN
•ALT = 2.5 x ULN
•Prothrombin time (PT) or INR = 1.5 x ULN partial thromboplastin time (PTT) or activated PTT (aPTT) = 1.5 x ULN
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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
1. The participant may not be enrolled in the study if any of the following applies: Patients who participated in other studies of anti-tumor therapy within 2 weeks before enrolment.
2. Patients with brain metastases.
3. Patients with poorly controlled hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 90 mmHg), or cardiovascular and cerebrovascular diseases with clinical significance, such as cerebrovascular accident (within 6 months before signing informed consent), myocardial infarction (within 6 months before signing
informed consent), unstable angina pectoris, congestive heart failure (New York Heart Association Class II or above), or severe arrhythmia, which cannot be controlled with drugs or have potential impact on treatment.
4. Patients with other serious organic diseases or mental disorders.
5. Patients with active infections, which cannot be controlled with drugs or have potential impact on treatment.
6. Patients with known history of human immunodeficiency virus (HIV).
7. Patients who have received an organ transplant and who are under continuous immunosuppression.
8. Use of immunosuppressive drugs like corticosteroids (excluding topical preparations)
within 30 days prior to the first TMV-018 injection or anticipated use before completion of study visit 6 (day 182).
9. Pregnancy (positive pregnancy test at screening or before end of study participation) or
lactation at screening or planning to become pregnant before completion of study
participation.
10. reliable contraception methods.
11. Patients with an impaired renal function (creatinine clearance = 40 mL/min).
12. Patients currently or recently (< 2 months) taking fluconazole, clotrimazole troches, itraconazole, amphotericin or other oral anti-fungal medications.
13. Known hypersensitivity to 5-FC or its excipients.
14. Known hypersensitivity to pembrolizumab, its excipients, or other monoclonal antibody.TMV-018-101 EudraCT 2019-003550-88 Protocol Final Version 1.3, 21-Nov-2019 Page 48/93
15. Severe immune-related adverse reactions from treatment with ipilimumab, defined as any grade 4 toxicity or grade3 toxicity requiring corticosteroid treatment (> 10 mg/day prednisone or equivalent) for greater than 12 weeks.
16. Patients with active autoimmune disease.
17. Other medical condition or laboratory abnormality that in the judgment of the Investigator may increase the risk associated with study participation or may interfere with
interpretation of study results.
18. History of severe systemic reaction or side-effect after a measles vaccination.
19. Known deficiency in dihydropyrimidine dehydrogenase (DPD) or total DPD deficiency
diagnosed at baseline in those patients not previously treated with 5-FU-related
compounds.
20. Subjects who continue to experience > grade 1 Common Terminology Criteria for Adverse Events (CTCAE) toxicity due to cancer therapy within 4 weeks prior to enrollment will not be eligible.
Note: Subjects with = grade 2 neuropathy and alopecia are an exception to this criterion.
21. Use of anti-cancer treatments within 4 weeks of TMV-018 treatment start:
• Chemotherapy (at least 4 weeks for e.g. 5-FU containing chemotherapies, oxaliplatin,
cisplatin, and taxanes).
• Agents targeting the vascular endothelial growth factor (VEGF) pathway (e.g., bevacizumab, ramucirumab, aflibercept, etc.), EGFR (e.g. cetuximab and panitumumab), Her2neu (e.g. trastuzumab).
• Other signal transduction inhibitors and monoclonal antibodies.
• I
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method