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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-000847-25 | EudraCT Number |
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The objective of this mechanistic study is to determine the impact of tecemotide (L-BLP25) administration on the mucinous glycoprotein 1 - (MUC1) specific immune response in subjects with newly diagnosed rectal cancer who are eligible for neoadjuvant therapy.
Tecemotide (L-BLP25) is designed to induce an immune response that may lead to immune rejection of tumor tissues that aberrantly express MUC1 antigen. MUC1 is highly expressed in all colorectal cancers and since the adaptive immune system plays a role in the prognosis of rectal cancer, it is reasonable to speculate that tecemotide (L-BLP25) administration might boost the tumor-specific immune response and increase the number of tumor-infiltrating lymphocytes (TILs).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chemoradiotherapy+tecemotide (L-BLP25)+CPA | Experimental |
| |
| Chemoradiotherapy+tecemotide (L-BLP25) | Experimental |
| |
| Chemoradiotherapy | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tecemotide (L-BLP25) | Biological | Subjects will receive 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 1, 2, 3, 4, 5, 6, 7 and 8, which will be administered concomitantly with the chemoradiotherapy, followed by a 9th subcutaneous injection 7 to 11 days prior to surgery. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Tumor Immune Response Evaluated by Immunohistochemical (IHC) Analysis of Tumor Infiltrating Lymphocytes (TILs) at Week 14 (Post-surgery) | Tumor biopsy samples were collected prior to baseline and after the surgery. The TILs were evaluated in 3 of the most abundant high-power fields (x40) per sample and the mean value considered (after excluding the lowest and the highest value). The tumor immune response was calculated as number of TILs divided by 100 tumor cells. | Baseline and Week 14 (post-surgery) |
| Immunological Response to Treatment in Relation to Microsatellite Instability (MSI) Status: Number of Subjects Per MSI Category | A potential association between MSI status (present or absent) and the primary endpoints (difference from baseline to surgery in CD8+ and CD8+/GrB+ T cell infiltration) was evaluated. Determination of mismatch repair protein (MRP)-expression (hMLH1, hMSH2, hMSH6 and hPMS2) was performed for the detection of the MSI-H-phenotype by IHC and/or on tumor deoxyribonucleic acid (DNA) sample using 5 microsatellite markers (BAT-25, BAT-26, NR-21, NR-24 and MONO-27). | 18 weeks |
| Change From Baseline in Interferon (IFN)-Gamma Secretion of Mononuclear Cells in Response to MUC1 by Enzyme-linked Immunosorbent Spot (ELISpot) at Post-baseline | IFN-gamma secretion of mononuclear cells in response to MUC1 was to be measured by ELISpot. The maximal post-baseline value out of Week 5, Week 11-13 (pre-surgery), and Week 16-18 (follow-up / end-of trial) was evaluated in comparison to Baseline. | Baseline, Week 5, Week 13 (pre-surgery), and Week 18 (end-of trial) |
| Change From Baseline in IFN-gamma Secretion of Mononuclear Cells in Response to Carcinoembryonic Antigen (CEA) by ELISpot at Post-baseline | IFN-gamma secretion of mononuclear cells in response to CEA was to be measured by ELISpot. The maximal post-baseline value out of Week 5, Week 11-13 (pre-surgery), and Week 16-18 (follow-up / end-of trial) was evaluated in comparison to Baseline. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Peritumoral Immune Response at Week 14 (Post-surgery) | Immunological changes in the tumor microenvironment were evaluated based on IHC expression of CD3+, CD4+, and Ki67+CD3+ T cells; regulatory T cells (FOXP3+) and myeloid-derived suppressor cells (CD33+CD14-); other immune cells such as NK cells (CD3-CD57+), B cells (CD20+), macrophages (CD68+), and dendritic cells (S100+). Peritumoral immune response was calculated as number of lymphoid cells at the margin of the tumor or in the tumor bed (if there is complete pathological response). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Barbara Guenther | Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| NKI (Nederlands Kanker Instituut) | Amsterdam | Netherlands |
Enrolled: 140 screened for eligibility; 16 excluded (mainly due to non-fulfillment of inclusion or exclusion criteria), 124 subjects randomized.
First/last participant (informed consent): Feb 2012/Dec 2013. Study completion date: Jun 2014.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Chemoradiotherapy+Tecemotide (L-BLP25)+CPA | Single dose of cyclophosphamide (300 mg/m^2 to a maximum of 600 mg) was administered intravenously, 3 days prior to the start of vaccination, followed by weekly subcutaneous vaccinations with tecemotide (L-BLP25) (actual delivered dose was 806 mcg) administered concomitantly with chemotherapy for 8 weeks, followed by a 9th subcutaneous vaccination 7 to 11 days prior to surgery. |
| FG001 | Chemoradiotherapy+Tecemotide (L-BLP25) | Weekly subcutaneous vaccinations with tecemotide (L-BLP25) (actual delivered dose was 806 mcg) administered concomitantly with chemotherapy for 8 weeks, followed by a 9th subcutaneous vaccination 7 to 11 days prior to surgery. |
| FG002 | Chemoradiotherapy | Radiotherapy of 45-52 Gy will be applied 5 times per week, over a minimum period of 5 weeks. Capecitabine at a dose of 825 mg/m^2, twice daily or equivalent dose of 5-FU will be given orally, starting at the first day of radiotherapy and given 5 to 7 days per week during the time of radiotherapy. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Safety analysis set included all subjects who received at least one dose of study treatment (tecemotide [L-BLP25] or CPA).
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Chemoradiotherapy+Tecemotide (L-BLP25)+CPA | Single dose of cyclophosphamide (300 mg/m^2 to a maximum of 600 mg) was administered intravenously, 3 days prior to the start of vaccination, followed by weekly subcutaneous vaccinations with tecemotide (L-BLP25) (actual delivered dose was 806 mcg) administered concomitantly with chemotherapy for 8 weeks, followed by a 9th subcutaneous vaccination 7 to 11 days prior to surgery. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Tumor Immune Response Evaluated by Immunohistochemical (IHC) Analysis of Tumor Infiltrating Lymphocytes (TILs) at Week 14 (Post-surgery) | Tumor biopsy samples were collected prior to baseline and after the surgery. The TILs were evaluated in 3 of the most abundant high-power fields (x40) per sample and the mean value considered (after excluding the lowest and the highest value). The tumor immune response was calculated as number of TILs divided by 100 tumor cells. | Immunomonitoring analysis set included all subjects for whom at least the baseline ELISpot blood and tumor sample, tumor sample at surgery and pre-surgery ELISpot blood drawing are available and whose tumor biopsy at baseline is MUC1-positive. Within the data table, n=number of subjects analyzed for each category. | Posted | Mean | Standard Deviation | TILs per 100 tumor cells | Baseline and Week 14 (post-surgery) |
|
Date of first signature of informed consent until the Follow-up/End-of-Trial visit (Week 18).
TEAEs: AE's during treatment; absent pre-treatment (PT)/worsened relative to PT & onset dates occurring from first trial treatment till the Follow-up/EOT. Safety Analysis Set included all randomized subjects; received at least 1 dose of treatment (arm A:one dose of CPA, arm B:one s.c. injection of tecemotide, arm C:neo-adjuvant chemoradiotherapy).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Chemoradiotherapy+Tecemotide (L-BLP25)+CPA | Single dose of cyclophosphamide (300 mg/m^2 to a maximum of 600 mg) was administered intravenously, 3 days prior to the start of vaccination, followed by weekly subcutaneous vaccinations with tecemotide (L-BLP25) (actual delivered dose was 806 mcg) administered concomitantly with chemotherapy for 8 weeks, followed by a 9th subcutaneous vaccination 7 to 11 days prior to surgery. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version17.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version17.0 | Non-systematic Assessment |
Not all efficacy data were analyzed as no acceptable ELISpot assay is available. The Sponsor decided to discontinue the development of tecemotide (L-BLP25) in September 2014
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck Serono, a division of Merck KGaA | +49-6151-72-5200 | service@merckgroup.com |
Not provided
| ID | Term |
|---|---|
| D012004 | Rectal Neoplasms |
| D009369 | Neoplasms |
| D009371 | Neoplasms by Site |
| D002277 | Carcinoma |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| C518273 | L-BLP25 |
| D003520 | Cyclophosphamide |
| D059248 | Chemoradiotherapy |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
Not provided
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Not provided
|
|
| cyclophosphamide (CPA) | Drug | A single intravenous infusion of 300 milligram per square meter (mg/m^2) (to a maximum 600 mg) of CPA will be given 3 days before the first tecemotide (L-BLP25) administration. |
|
|
| Chemoradiotherapy | Other | Radiotherapy of 45-52 grays (Gy) will be applied 5 times per week, over a minimum period of 5 weeks. Capecitabine at a dose of 825 mg/m^2, twice daily or equivalent dose of 5-fluorouracil (5-FU) will be given orally, starting at the first day of radiotherapy and given 5 to 7 days per week during the time of radiotherapy. |
|
| Baseline, Week 5, Week 13 (pre-surgery), and Week 18 (end-of trial) |
| Baseline and Week 14 (post-surgery) |
| Change From Baseline in Immunological Response in Peripheral Blood at Week 18 (Follow-up / end-of Trial) | Immunological changes in peripheral blood were evaluated based on fluorescence analysis cell sorter phenotypic characterization of T cells (CD3+CD4+ and CD3+CD8+) and of markers of activation and proliferation (CD27, BTLA); and regulatory cells such as CD3+CD4+ (or CD8+) CD45RA+CD25+FoxP3+CD127 T cells. Immunological Response in peripheral blood was measured on a continuous scale. | Baseline and Week 18 (follow-up / end-of trial) |
| BG001 | Chemoradiotherapy+Tecemotide (L-BLP25) | Weekly subcutaneous vaccinations with tecemotide (L-BLP25) (actual delivered dose was 806 mcg) administered concomitantly with chemotherapy for 8 weeks, followed by a 9th subcutaneous vaccination 7 to 11 days prior to surgery. |
| BG002 | Chemoradiotherapy | Radiotherapy of 45-52 Gy will be applied 5 times per week, over a minimum period of 5 weeks. Capecitabine at a dose of 825 mg/m^2, twice daily or equivalent dose of 5-FU will be given orally, starting at the first day of radiotherapy and given 5 to 7 days per week during the time of radiotherapy. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Gender | Count of Participants | Participants |
|
Single dose of cyclophosphamide (300 mg/m^2 to a maximum of 600 mg) was administered intravenously, 3 days prior to the start of vaccination, followed by weekly subcutaneous vaccinations with tecemotide (L-BLP25) (actual delivered dose was 806 mcg) administered concomitantly with chemotherapy for 8 weeks, followed by a 9th subcutaneous vaccination 7 to 11 days prior to surgery. |
| OG001 | Chemoradiotherapy+Tecemotide (L-BLP25) | Weekly subcutaneous vaccinations with tecemotide (L-BLP25) (actual delivered dose was 806 mcg) administered concomitantly with chemotherapy for 8 weeks, followed by a 9th subcutaneous vaccination 7 to 11 days prior to surgery. |
| OG002 | Chemoradiotherapy | Radiotherapy of 45-52 Gy will be applied 5 times per week, over a minimum period of 5 weeks. Capecitabine at a dose of 825 mg/m^2, twice daily or equivalent dose of 5-FU will be given orally, starting at the first day of radiotherapy and given 5 to 7 days per week during the time of radiotherapy. |
|
|
|
| Primary | Immunological Response to Treatment in Relation to Microsatellite Instability (MSI) Status: Number of Subjects Per MSI Category | A potential association between MSI status (present or absent) and the primary endpoints (difference from baseline to surgery in CD8+ and CD8+/GrB+ T cell infiltration) was evaluated. Determination of mismatch repair protein (MRP)-expression (hMLH1, hMSH2, hMSH6 and hPMS2) was performed for the detection of the MSI-H-phenotype by IHC and/or on tumor deoxyribonucleic acid (DNA) sample using 5 microsatellite markers (BAT-25, BAT-26, NR-21, NR-24 and MONO-27). | Immunomonitoring analysis set included all subjects for whom at least the baseline ELISpot blood and tumor sample, tumor sample at surgery and pre-surgery ELISpot blood drawing are available and whose tumor biopsy at baseline is MUC1-positive. | Posted | Number | subjects | 18 weeks |
|
|
|
|
| Primary | Change From Baseline in Interferon (IFN)-Gamma Secretion of Mononuclear Cells in Response to MUC1 by Enzyme-linked Immunosorbent Spot (ELISpot) at Post-baseline | IFN-gamma secretion of mononuclear cells in response to MUC1 was to be measured by ELISpot. The maximal post-baseline value out of Week 5, Week 11-13 (pre-surgery), and Week 16-18 (follow-up / end-of trial) was evaluated in comparison to Baseline. | Data were not analyzed as no acceptable ELISpot assay is available | Posted | Baseline, Week 5, Week 13 (pre-surgery), and Week 18 (end-of trial) |
|
|
| Secondary | Change From Baseline in Peritumoral Immune Response at Week 14 (Post-surgery) | Immunological changes in the tumor microenvironment were evaluated based on IHC expression of CD3+, CD4+, and Ki67+CD3+ T cells; regulatory T cells (FOXP3+) and myeloid-derived suppressor cells (CD33+CD14-); other immune cells such as NK cells (CD3-CD57+), B cells (CD20+), macrophages (CD68+), and dendritic cells (S100+). Peritumoral immune response was calculated as number of lymphoid cells at the margin of the tumor or in the tumor bed (if there is complete pathological response). | The pre-specified statistical threshold for reporting of results of planned analysis for either arm or interaction effect was not met in the analysis population. Hence the data was not assessed for the outcome measure. | Posted | Baseline and Week 14 (post-surgery) |
|
|
| Secondary | Change From Baseline in Immunological Response in Peripheral Blood at Week 18 (Follow-up / end-of Trial) | Immunological changes in peripheral blood were evaluated based on fluorescence analysis cell sorter phenotypic characterization of T cells (CD3+CD4+ and CD3+CD8+) and of markers of activation and proliferation (CD27, BTLA); and regulatory cells such as CD3+CD4+ (or CD8+) CD45RA+CD25+FoxP3+CD127 T cells. Immunological Response in peripheral blood was measured on a continuous scale. | Immunomonitoring analysis set included all subjects for whom at least the baseline ELISpot blood and tumor sample, tumor sample at surgery and pre-surgery ELISpot blood drawing are available and whose tumor biopsy at baseline is MUC1-positive. Within the data table, n=number of subjects analysed for each category. | Posted | Mean | Standard Deviation | log2 (percentage of T cells) | Baseline and Week 18 (follow-up / end-of trial) |
|
|
|
| Primary | Change From Baseline in IFN-gamma Secretion of Mononuclear Cells in Response to Carcinoembryonic Antigen (CEA) by ELISpot at Post-baseline | IFN-gamma secretion of mononuclear cells in response to CEA was to be measured by ELISpot. The maximal post-baseline value out of Week 5, Week 11-13 (pre-surgery), and Week 16-18 (follow-up / end-of trial) was evaluated in comparison to Baseline. | Data were not analyzed as no acceptable ELISpot assay is available | Posted | Baseline, Week 5, Week 13 (pre-surgery), and Week 18 (end-of trial) |
|
|
| 10 |
| 39 |
| 38 |
| 39 |
| EG001 | Chemoradiotherapy+Tecemotide (L-BLP25) | Weekly subcutaneous vaccinations with tecemotide (L-BLP25) (actual delivered dose was 806 mcg) administered concomitantly with chemotherapy for 8 weeks, followed by a 9th subcutaneous vaccination 7 to 11 days prior to surgery. | 10 | 41 | 41 | 41 |
| EG002 | Chemoradiotherapy | Radiotherapy of 45-52 Gy will be applied 5 times per week, over a minimum period of 5 weeks. Capecitabine at a dose of 825 mg/m^2, twice daily or equivalent dose of 5-FU will be given orally, starting at the first day of radiotherapy and given 5 to 7 days per week during the time of radiotherapy. | 12 | 42 | 41 | 42 |
| Coagulopathy | Blood and lymphatic system disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Gastrointestinal necrosis | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Peritoneal haemorrhage | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Impaired healing | General disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Injection site reaction | General disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Abdominal abscess | Infections and infestations | MedDRA Version17.0 | Non-systematic Assessment |
|
| Anal abscess | Infections and infestations | MedDRA Version17.0 | Non-systematic Assessment |
|
| Catheter site infection | Infections and infestations | MedDRA Version17.0 | Non-systematic Assessment |
|
| Gastrointestinal infection | Infections and infestations | MedDRA Version17.0 | Non-systematic Assessment |
|
| Pelvic infection | Infections and infestations | MedDRA Version17.0 | Non-systematic Assessment |
|
| Peritonitis | Infections and infestations | MedDRA Version17.0 | Non-systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA Version17.0 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA Version17.0 | Non-systematic Assessment |
|
| Wound infection bacterial | Infections and infestations | MedDRA Version17.0 | Non-systematic Assessment |
|
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA Version17.0 | Non-systematic Assessment |
|
| Anastomotic leak | Injury, poisoning and procedural complications | MedDRA Version17.0 | Non-systematic Assessment |
|
| Gastrointestinal anastomotic leak | Injury, poisoning and procedural complications | MedDRA Version17.0 | Non-systematic Assessment |
|
| Gastrointestinal stoma complication | Injury, poisoning and procedural complications | MedDRA Version17.0 | Non-systematic Assessment |
|
| Post procedural complication | Injury, poisoning and procedural complications | MedDRA Version17.0 | Non-systematic Assessment |
|
| Procedural intestinal perforation | Injury, poisoning and procedural complications | MedDRA Version17.0 | Non-systematic Assessment |
|
| Radiation skin injury | Injury, poisoning and procedural complications | MedDRA Version17.0 | Non-systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA Version17.0 | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Hypovolaemia | Metabolism and nutrition disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Coccydynia | Musculoskeletal and connective tissue disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Peritumoural oedema | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version17.0 | Non-systematic Assessment |
|
| Central nervous system lesion | Nervous system disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Hemiplegia | Nervous system disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Ischaemic stroke | Nervous system disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Renal colic | Renal and urinary disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Female genital tract fistula | Reproductive system and breast disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Aortic thrombosis | Vascular disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Anorectal discomfort | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Defaecation urgency | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Faecal incontinence | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Gastrointestinal pain | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Painful defaecation | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Rectal tenesmus | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Chills | General disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Injection site haematoma | General disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Injection site induration | General disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Injection site nodule | General disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Injection site pain | General disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Injection site reaction | General disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA Version17.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA Version17.0 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA Version17.0 | Non-systematic Assessment |
|
| Procedural nausea | Injury, poisoning and procedural complications | MedDRA Version17.0 | Non-systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA Version17.0 | Non-systematic Assessment |
|
| Radiation skin injury | Injury, poisoning and procedural complications | MedDRA Version17.0 | Non-systematic Assessment |
|
| Antinuclear antibody increased | Investigations | MedDRA Version17.0 | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA Version17.0 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Urinary tract pain | Renal and urinary disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA Version17.0 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA Version17.0 | Non-systematic Assessment |
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The Investigator will inform the Sponsor in advance about any plans to publish or present data from the trial. Any publications and presentations of the results (abstracts in journals or newspapers, oral presentations, etc.), either in whole or in part, by Investigators or their representatives will require pre-submission review by the Sponsor.
The Sponsor will not suppress or veto publications, but maintains the right to delay publication in order to protect intellectual property rights.
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D003131 | Combined Modality Therapy |
| D013812 | Therapeutics |
| D004358 | Drug Therapy |
| D011878 | Radiotherapy |
| Title | Measurements |
|---|---|
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| Superiority or Other |
| Category: CD8+ The difference in T cell infiltration from baseline to surgery was analysed and compared across the 3 treatment arms (effect estimate for Arm B vs Arm C) based on an ANCOVA model. Difference from baseline = Surgery value-Baseline value. Adjustment was based on ANCOVA model with treatment arm as factor and baseline value and MSI category as covariates. No interaction included. Pairwise tests have been performed to compare Arm A with Arm C, Arm B with Arm C, and Arm A with Arm B. | type III SS F-test | 0.921 | LS Means estimate | -0.20 | 2-Sided | 95 | -0.83 | 0.44 | Difference between Means adjusted on covariates baseline value and MSI category. | No | Superiority or Other |
| Category: CD8+ The difference in T cell infiltration from baseline to surgery was analysed and compared across the 3 treatment arms (effect estimate for Arm A vs Arm B) based on an ANCOVA model. Difference from baseline = Surgery value-Baseline value. Adjustment was based on ANCOVA model with treatment arm as factor and baseline value and MSI category as covariates. No interaction included. Pairwise tests have been performed to compare Arm A with Arm C, Arm B with Arm C, and Arm A with Arm B. | type III SS F-test | 0.921 | LS Means estimate | 0.17 | 2-Sided | 95 | -0.50 | 0.83 | Difference between Means adjusted on covariates baseline value and MSI category. | No | Superiority or Other |
| Category:CD8+/GrB+ The difference in T cell infiltration from baseline to surgery was analysed and compared across the 3 treatment arms (effect estimate for Arm A vs Arm C) based on an ANCOVA model. Difference from baseline=Surgery value-Baseline value. Adjustment was based on ANCOVA model with treatment arm as factor and baseline value and MSI category as covariates. No interaction included. Pairwise tests have been performed to compare Arm A with Arm C, Arm B with Arm C, and Arm A with Arm B. | type III SS F-test | 0.890 | LS Means estimate | 0.02 | 2-Sided | 95 | -0.54 | 0.58 | Difference between Means adjusted on covariates baseline value and MSI category. | No | Superiority or Other |
| Category:CD8+/GrB+ The difference in T cell infiltration from baseline to surgery was analysed and compared across the 3 treatment arms (effect estimate for Arm B vs Arm C) based on an ANCOVA model. Difference from baseline=Surgery value-Baseline value. Adjustment was based on ANCOVA model with treatment arm as factor and baseline value and MSI category as covariates. No interaction included. Pairwise tests have been performed to compare Arm A with Arm C, Arm B with Arm C, and Arm A with Arm B. | type III SS F-test | 0.890 | LS Means estimate | -0.19 | 2-Sided | 95 | -0.70 | 0.31 | Difference between Means adjusted on covariates baseline value and MSI category. | No | Superiority or Other |
| Category:CD8+/GrB+ The difference in T cell infiltration from baseline to surgery was analysed and compared across the 3 treatment arms (effect estimate for Arm A vs Arm B) based on an ANCOVA model. Difference from baseline=Surgery value-Baseline value. Adjustment was based on ANCOVA model with treatment arm as factor and baseline value and MSI category as covariates. No interaction included. Pairwise tests have been performed to compare Arm A with Arm C, Arm B with Arm C, and Arm A with Arm B. | type III SS F-test | 0.890 | LS Means estimate | 0.21 | 2-Sided | 95 | -0.32 | 0.74 | Difference between Means adjusted on covariates baseline value and MSI category. | No | Superiority or Other |
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| CD3+CD4+CD27+ (n=26,30,24) |
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| CD3-CD56+CD16+Granzyme B+/LY (n=26,30,24) |
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| CD3-CD56+CD16+Perforin+/LY (n=26,30,24) |
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| CD3-CD56+CD16-CD107a+ (n=26,30,24) |
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| CD3+CD8+CD127-FoxP3-CD45RA-CD25+CTLA4+(n=27,29,24) |
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| CD3+CD56+CD16-Granzyme B+ (n=26,30,24) |
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| CD3-CD56+CD16+/LY (n=26,30,24) |
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| CD3-CD19+BTLA4+ (n=27,29,23) |
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| Lymphs Tube 2 (n=27,30,25) |
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| CD3+CD56+CD16+CD107a+ (n=26,30,24) |
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| CD3+CD4+BTLA4+ (n=26,30,24) |
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| Lymphs Tube 3 (n=27,30,25) |
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| CD3+CD56+CD16+CCR7+ (n=26,30,24) |
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| CD3+CD8+CD127+FoxP3-CD25-CD45RA+CTLA4-(n=27,29,24) |
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| Background corrected CD3+CD4+IFNg+ (n=21,27,21) |
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| CD3+CD56+CD16+Granzyme B+/LY (n=26,30,24) |
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| CD3+CD56+CD16+Perforin+/LY (n=26,30,24) |
|
| CD3+CD4+CD127+FoxP3-CD45RA-CD25+CTLA4+(n=27,29,24) |
|