E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006202 |
E.1.2 | Term | Breast cancer stage IV |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the tumor responses to SNDX-275 in combination with continued AI therapy as measured by clinical benefit rate (CBR) during the first 6 cycles of study treatment, i.e., complete response (CR), partial response (PR), or stable disease (SD) for at least 6 months. |
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E.2.2 | Secondary objectives of the trial |
Efficacy: To evaluate progression free survival (PFS) and objective response rates (ORR) of SNDX-275 during the first 6 cycles of study treatment when administered in combination with continued AI.
Safety: To evaluate the safety and tolerability of SNDX-275 when administered in combination with continued AI therapy as measured by clinical adverse events and laboratory parameters.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Postmenopausal female patients. 2. Histolologically or cytologically confirmed ER+ breast cancer. 3. Progressive disease (PD) after at least 3 months on treatment with a 3rd generation AI in the advanced disease setting as measured by RECIST criteria. 4. At least 1 measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan with the last imaging performed within 4 weeks prior to study entry. If there is only one measurable lesion and it is located in previously irradiated field, it must have demonstrated progression according to RECIST criteria. 5. ECOG 0-1. 6. Laboratory parameters: a) Hemoglobin ≥ 9.0 g/dL; platelets ≥ 100 x109/L; ANC ≥ 1.5 x 109/L without the use of hematopoietic growth factors. b) Creatinine less than 2.5 times the upper limit of normal for the institution. c) AST and ALT less than 2.5 times the upper limit of normal for the institution. 7. Able to understand and give written informed consent and comply with study procedures.
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E.4 | Principal exclusion criteria |
1. Discontinuation of AI therapy prior to study entry. 2. Less than 3 months treatment with most recent AI. 3. Rapidly progressive, life-threatening metastases, including any of the following: a) Symptomatic lymphangitic metastases. b) Patients with known active brain or leptomeningeal involvement. 4. More than one prior chemotherapy for metastatic disease. 5. Any chemotherapy within 3 months prior to study. 6. Radiotherapy to measurable lesion within 2 months prior to study. 7. Bisphosphonates initiated within 4 weeks prior to study start. 8. Allergy to benzamides or inactive components of study drug. 9. Previous treatment with SNDX-275 or any other HDAC inhibitor including valproic acid. 10. Patient is currently receiving treatment with any agent listed on the prohibited medication list such as valproic acid, other systemic cancer agents (with the exception of approved luteinising-hormone releasing hormone (LHRH) agonists such as godserelin or leuproelin. See Section 6.6 for complete list. 11. Any concomitant medical condition that precludes adequate study treatment compliance or assessment, or increases patient risk in the opinion of the investigator: a) Myocardial infarction or arterial thromboembolic events within 6 months, or experiencing severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease and a QTc interval >0.47 second. b) Uncontrolled heart failure or hypertension, uncontrolled diabetes mellitus, uncontrolled systemic infection, c) Other active malignancy within 5 years excluding basal cell carcinoma or cervical intraepithelial neoplasia [CIN / cervical carcinoma in situ] or melanoma in situ). 12. Patient currently is enrolled in (or completed within 30 days before study drug administration) another investigational drug study
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical benefit rate (CBR) during the first 6 cycles of study treatment, i.e., CR/PR/SD ≥ 6 months, according to RECIST criteria. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |