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| ID | Type | Description | Link |
|---|---|---|---|
| CAAA113A42202 | Other Identifier | Novartis |
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Sponsor Decision based on strategic considerations
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This was a single center, proof-of-concept (PoC), Phase II study. Patients with histologically confirmed early stage (Stage I, II or III) HER-2 negative breast cancer and scheduled to receive doxorubicin-based (neo)adjuvant therapy to be followed by paclitaxel or docetaxel as per clinical practice. The planned doxorubicin-based chemotherapy treatment consisted of doxorubicin 60 mg/m2 in combination with cyclophosphamide 600 mg/m2 (AC) intravenous (IV) every 2 or 3 weeks for 4 cycles. Patients were scheduled for CMRI and 99mTc-rhAnnexin V-128 imaging (planar and SPECT / CT) at the following visits:
Overall, it was planned to recruit 30 adults with early stage breast cancer. The first 10 patients were to be enrolled in the PoC phase of the study to assess the potential of 99mTc-rhAnnexin V-128 in terms of imaging quality, uptake and medical relevance. Based on the results of the first 10 patients, the DMC was to decide whether to terminate the study or continue to the Phase II and enroll the next 20 planned patients. The maximum study duration was 26 (±4) weeks per patient (including the screening and follow-up periods).
The sponsor decided to terminate the study earlier than planned due to strategic decisions to focus the AAA development portfolio on oncology theragnostics and not based on safety concerns.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with breast cancer receiving chemotherapy | Experimental | After reconstitution and radiolabeling, 99mTc-rhAnnexin V-128 was administered as a single intravenous bolus of 350 MBq +/- 10% at baseline, after the 2nd cycle, after the 4th cycle and 12 weeks after AC chemotherapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 99mTc-rhAnnexin V-128 | Radiation | Kit for the preparation of 99mTc-rhAnnexin V-128 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part I / Proof of Concept (PoC): Number of Participants Evaluated for Imaging Feasibility | The feasibility of imaging apoptotic activity using 99mTc-rhAnnexin V-128 was assessed in the first 10 patients who enrolled and completed the PoC phase of the study by the data monitoring committee (visual image review and consensus). The three reviewers of the DMC did an independent visual assessment of the images using a 1 to 4 point grading system: each observer reviewed the images of each patient and scored either 1 or 2 (uptake was less than or equal to blood pool), these images were considered normal; 3 was equivocal and four equalled abnormal. Only descriptive analysis performed. | Day 0 (Baseline) |
| Measure | Description | Time Frame |
|---|---|---|
| 99mTc-rhAnnexin V-128 Myocardial Uptake | Single-Photon Emission Computed Tomography (SPECT)/Computed Tomography (CT) scans of the thorax were acquired with a dual head SPECT/CT gamma camera with low-energy high-resolution collimators at 1 and 2 hours post-injection at each collection time point and were to be compared to Baseline. Myocardial uptake was measured from regions of interest (ROIs) placed over the myocardium on the SPECT images coregistered with the corresponding CT images for anatomic delineation. Myocardial uptake was expressed either in absolute units (% injected dose/g) or as a standardized uptake value (SUV). Only descriptive analysis performed. |
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Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Ottawa Heart Institute | Ottawa | Ontario | K1Y 4W7 | Canada |
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The study was conducted at single center in Canada.
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| ID | Title | Description |
|---|---|---|
| FG000 | 99mTc-rhAnnexin V-128 (Part I / Proof of Concept) | After reconstitution and radiolabeling, 99mTc-rhAnnexin V-128 was administered as a single intravenous bolus of 350 MBq +/- 10% at baseline, after the 2nd cycle, after the 4th cycle and 12 weeks after AC chemotherapy. |
| FG001 | 99mTc-rhAnnexin V-128 (Part II / Phase II) | After reconstitution and radiolabeling, 99mTc-rhAnnexin V-128 was administered as a single intravenous bolus of 350 MBq +/- 10% at baseline, after the 2nd cycle, after the 4th cycle and 12 weeks after AC chemotherapy. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 99mTc-rhAnnexin V-128 (Part I / Proof of Concept) | After reconstitution and radiolabeling, 99mTc-rhAnnexin V-128 was administered as a single intravenous bolus of 350 MBq +/- 10% at baseline, after the 2nd cycle, after the 4th cycle and 12 weeks after AC chemotherapy. |
| BG001 | 99mTc-rhAnnexin V-128 (Part II / Phase II) |
| 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 | Part I / Proof of Concept (PoC): Number of Participants Evaluated for Imaging Feasibility | The feasibility of imaging apoptotic activity using 99mTc-rhAnnexin V-128 was assessed in the first 10 patients who enrolled and completed the PoC phase of the study by the data monitoring committee (visual image review and consensus). The three reviewers of the DMC did an independent visual assessment of the images using a 1 to 4 point grading system: each observer reviewed the images of each patient and scored either 1 or 2 (uptake was less than or equal to blood pool), these images were considered normal; 3 was equivocal and four equalled abnormal. Only descriptive analysis performed. | Full Analysis Set population (FAS). Only the first 10 participants who enrolled and completed the PoC phase of the study were included in the analysis. | Posted | Count of Participants | Participants | Day 0 (Baseline) |
|
From the signing of the informed consent until the last study-related procedure (up to 12 weeks)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 99mTc-rhAnnexin V-128 (Part I / Proof of Concept) | After reconstitution and radiolabeling, 99mTc-rhAnnexin V-128 was administered as a single intravenous bolus of 350 MBq +/- 10% at baseline, after the 2nd cycle, after the 4th cycle and 12 weeks after AC chemotherapy. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version: 19.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA Version: 19.0 | Systematic Assessment |
Due to the early termination of the trial and the fact that only 2 patients were enrolled in the Phase II of the study, the efficacy endpoints of the trial were not addressed (summary statistics were not performed).
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | Novartis.email@novartis.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 11, 2018 | Apr 24, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 22, 2019 | Apr 24, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| 60 and 120 minutes post injection at: Day 0 (Baseline), Visit 2 (After the 2nd and before the 3rd cycle of doxorubicin), Visit 3 (After the 4th cycle of doxorubicin and within 2 weeks), Visit 4 (12 weeks after the 4th cycle of doxorubicin) |
| Changes in Left Ventricular (LV) Function | The worsening of LV function was to be assessed by comparing cardiac magnetic resonance imaging (CMRI) left ventricular ejection fraction (LVEF) after the 2nd and the 4th cycle of doxorubicin/cyclophosphamide chemotherapy (AC) treatment and after 12 weeks of the last dose of doxorubicin compared to Baseline. Only descriptive analysis performed. | Day 0 (Baseline), Visit 2 (After the 2nd and before the 3rd cycle of doxorubicin), Visit 3 (After the 4th cycle of doxorubicin and within 2 weeks), Visit 4 (12 weeks after the 4th cycle of doxorubicin) |
| Changes in the Cardiotoxicity Biomarkers (Troponin and NT-proBNP) | The differences of LV function after the 2nd and the 4th cycle of doxorubicin/cyclophosphamide chemotherapy (AC) treatment and after 12 weeks of the last dose of doxorubicin compared to Baseline were to be correlated with the changes in cardiotoxicity biomarkers: Troponin and N Terminal pro B-type Natriuretic Peptide (NT-proBNP). Only descriptive analysis performed. | Day 0 (Baseline), Visit 2 (After the 2nd and before the 3rd cycle of doxorubicin), Visit 3 (After the 4th cycle of doxorubicin and within 2 weeks), Visit 4 (12 weeks after the 4th cycle of doxorubicin) |
After reconstitution and radiolabeling, 99mTc-rhAnnexin V-128 was administered as a single intravenous bolus of 350 MBq +/- 10% at baseline, after the 2nd cycle, after the 4th cycle and 12 weeks after AC chemotherapy. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
After reconstitution and radiolabeling, 99mTc-rhAnnexin V-128 was administered as a single intravenous bolus of 350 MBq +/- 10% at baseline, after the 2nd cycle, after the 4th cycle and 12 weeks after AC chemotherapy. |
|
|
| Secondary | 99mTc-rhAnnexin V-128 Myocardial Uptake | Single-Photon Emission Computed Tomography (SPECT)/Computed Tomography (CT) scans of the thorax were acquired with a dual head SPECT/CT gamma camera with low-energy high-resolution collimators at 1 and 2 hours post-injection at each collection time point and were to be compared to Baseline. Myocardial uptake was measured from regions of interest (ROIs) placed over the myocardium on the SPECT images coregistered with the corresponding CT images for anatomic delineation. Myocardial uptake was expressed either in absolute units (% injected dose/g) or as a standardized uptake value (SUV). Only descriptive analysis performed. | Full Analysis Set population (FAS). Only the participants who completed the 4 chemotherapy treatment cycles and underwent all study visits were included in the analysis. | Posted | Mean | Standard Deviation | percentage of injected dose/g | 60 and 120 minutes post injection at: Day 0 (Baseline), Visit 2 (After the 2nd and before the 3rd cycle of doxorubicin), Visit 3 (After the 4th cycle of doxorubicin and within 2 weeks), Visit 4 (12 weeks after the 4th cycle of doxorubicin) |
|
|
|
| Secondary | Changes in Left Ventricular (LV) Function | The worsening of LV function was to be assessed by comparing cardiac magnetic resonance imaging (CMRI) left ventricular ejection fraction (LVEF) after the 2nd and the 4th cycle of doxorubicin/cyclophosphamide chemotherapy (AC) treatment and after 12 weeks of the last dose of doxorubicin compared to Baseline. Only descriptive analysis performed. | Full Analysis Set population (FAS). Only the participants who completed the 4 chemotherapy treatment cycles and underwent all study visits were included in the analysis. | Posted | Mean | Standard Deviation | Percent | Day 0 (Baseline), Visit 2 (After the 2nd and before the 3rd cycle of doxorubicin), Visit 3 (After the 4th cycle of doxorubicin and within 2 weeks), Visit 4 (12 weeks after the 4th cycle of doxorubicin) |
|
|
|
| Secondary | Changes in the Cardiotoxicity Biomarkers (Troponin and NT-proBNP) | The differences of LV function after the 2nd and the 4th cycle of doxorubicin/cyclophosphamide chemotherapy (AC) treatment and after 12 weeks of the last dose of doxorubicin compared to Baseline were to be correlated with the changes in cardiotoxicity biomarkers: Troponin and N Terminal pro B-type Natriuretic Peptide (NT-proBNP). Only descriptive analysis performed. | Full Analysis Set population (FAS). For each parameter, only participants with a value at both baseline and post baseline were included in the analysis. | Posted | Mean | Standard Deviation | ng/L | Day 0 (Baseline), Visit 2 (After the 2nd and before the 3rd cycle of doxorubicin), Visit 3 (After the 4th cycle of doxorubicin and within 2 weeks), Visit 4 (12 weeks after the 4th cycle of doxorubicin) |
|
|
|
| 0 |
| 12 |
| 1 |
| 12 |
| 10 |
| 12 |
| EG001 | 99mTc-rhAnnexin V-128 (Part II / Phase II) | After reconstitution and radiolabeling, 99mTc-rhAnnexin V-128 was administered as a single intravenous bolus of 350 MBq +/- 10% at baseline, after the 2nd cycle, after the 4th cycle and 12 weeks after AC chemotherapy. | 0 | 2 | 1 | 2 | 2 | 2 |
| Pyrexia | Gastrointestinal disorders | MedDRA Version: 19.0 | Systematic Assessment |
|
| Carbuncle | Infections and infestations | MedDRA Version: 19.0 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA Version: 19.0 | Systematic Assessment |
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| Escherichia urinary tract infection | Infections and infestations | MedDRA Version: 19.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA Version: 19.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Delirium | Psychiatric disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Hypoacusis | Ear and labyrinth disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Duodenogastric reflux | Gastrointestinal disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Dysgeusia | Gastrointestinal disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Oesophagitis | Gastrointestinal disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Febrile neutropenia | General disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Oral candidiasis | Infections and infestations | MedDRA Version: 19.0 | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | MedDRA Version: 19.0 | Systematic Assessment |
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| Fluid retention | Metabolism and nutrition disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version: 19.0 | Systematic Assessment |
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| Insomnia | Nervous system disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Neuropathy peripheral | Nervous system disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Peripheral sensory neuropathy | Nervous system disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Sleep disorder due to general medical condition, insomnia type | Psychiatric disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Herpes zoster | Skin and subcutaneous tissue disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA Version: 19.0 | Systematic Assessment |
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| Skin candida | Skin and subcutaneous tissue disorders | MedDRA Version: 19.0 | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
| D017437 |
| Skin and Connective Tissue Diseases |
| Visit 2 - 60 mins after injection |
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| Visit 2 - 120 mins after injection |
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| Visit 3 - 60 mins after injection |
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| Visit 3 - 120 mins after injection |
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| Visit 4 - 60 mins after injection |
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| Visit 4 - 120 mins after injection |
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| Visit 3 |
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| Visit 4 |
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| Troponin - Visit 2 |
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| Troponin - Visit 3 |
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| Troponin - Visit 4 |
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| NT-proBNP - Day 0 |
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| NT-proBNP - Visit 2 |
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| NT-proBNP - Visit 3 |
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| NT-proBNP - Visit 4 |
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