Rectal Cancer Patients
Conditions
Keywords
Rectal Cancer, Immunotherapy, Oncolytic Virotherapy, Proficient mismatch repair
Brief summary
A Phase I clinical trial that will investigate the safety and tolerability of combining the modified vaccinia virus BT-001 with systemic pembrolizumab in patients with localised pMMR rectal cancer
Interventions
DRUGBT-001 followed by Pembrolizumab (PD-1 Blocking Antibody)
Two doses of BT-001 delivered by intra-tumoural injection followed by one systemic dose of pembrolizumab
Sponsors
Henry Smith
Transgene
Rigshospitalet, Denmark
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological diagnosis of primary, localised rectal adenocarcinoma (cT2N0M0 to cT3bN2M0, TNM classification version 8 * Diagnosis of Proficient Mismatch Repair (pMMR) rectal adenocarcinoma (using biopsy from the initial diagnostic endoscopy) * Suitable for potentially curative surgical resection * No contraindications for treatment with pembrolizumab * Not requiring neoadjuvant therapy * Aged \> 18 years at the time of inclusion * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Have baseline laboratory results as follows: * Absolute neutrophil count (ANC) ≥ 1.0 x 109/L * Platelets ≥ 100 ×109/L (without platelet transfusion) * Haemoglobin ≥ 6.2 mmol/L or 10.0 g/dL (with or without red blood cell (RBC) transfusion) * Serum creatinine ≤ 1.5 × upper limit of normal (ULN) * Bilirubin \< 1.5 × ULN (or \< 2.5 x ULN in patients with Gilbert's syndrome) * ALT, AST and alkaline phosphatase \< 3 × ULN * Provide written informed consent in accordance with all applicable regulations and follow the study procedures. Subjects must be capable of understanding the investigational nature, potential risks, and benefits of the study.
Exclusion criteria
* Have impending bowel obstruction or other indications for acute surgical intervention * Have had concurrent immunotherapy in the 3 months before the start of the study therapy. * Have acute or chronic hepatitis B or hepatitis C infection * Evidence of immunosuppression for any reason: * Known HIV disease * Chronic oral or systemic steroid medication use at a dose of \> 10 mg/day of prednisolone or equivalent * Other signs or symptoms of clinical immune system suppression * Have an autoimmune disorder (except thyroiditis with replacement therapy and type I diabetes mellitus) * Have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease * Ongoing antiviral therapy active on vaccinia virus, e.g., ribavirin, cidofovir, interferon/ pegylated interferon * History of severe exfoliative skin conditions (e.g., eczema or atopic dermatitis) requiring systemic therapy for more than 4 weeks within 2 years prior to BT-001 initiation * Live virus vaccination within 28 days of BT-001 administration * A history of hypersensitivity to egg or to any excipient of BT-001 * Pregnant or breast-feeding female. Confirmation that women of childbearing potential are not pregnant with a negative serum β-human chorionic gonadotrophin (β-hCG) pregnancy test results must be obtained within 7 days prior to the 1st administration of BT-001 * Fertile males and females who are unwilling to employ highly effective means of contraception during study treatment and for 4 months after the last dose of study treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall incidence of adverse events (AEs) | Within 30 days of the end of the study treatment | Evaluated according to National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
| Overall incidence of serious adverse events (SAEs) | Within 30 days of the end of the study treatment | Evaluated according to National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
| Overall incidence of dose limiting toxicities (DLTs) | Within 30 days of the end of the study treatment | Incidence of dose-limiting toxicities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical efficacy of BT-001 when delivered by endoscopic/transrectal ultrasound guided intra-tumoural injection in combination with a single systemic dose of pembrolizumab in patients with primary, localised, rectal cancer with proficient mismatch repair | Within 6 weeks of the start of the study treatment | Defined as the proportion of patients achieving a complete or major pathological response. |
| Effects of the study treatment on long-term oncological outcomes | Up to 5 years after the end of the study treatment | Percentage of patients developing local recurrence and/or distant metastases at 1-, 3- and 5-years' follow-up |
| Determine the effects of the study treatment on patient's quality of life | Up to 5 years after the end of the study treatment | Assessed using the EORTC QLQ (European Organisation for Research and Treatment of Cancer Qulaity of Life Questionaire) CR29 questionnaire at baseline, 1 month after surgery, and 1-, 3- and 5-years' follow-up. Higher score means a poorer outcome. Minimum score 29, maximum score 116. |
Countries
Denmark
Contacts
CONTACTHenry G Smith, PhD
Outcome results
None listed