E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006178 |
E.1.2 | Term | Breast adenocarcinoma stage IV |
|
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 assess the effect of letrozole plus PD 0332991 and of letrozole alone on progression-free survival (PFS) in the first line treatment of ER+, HER2 negative ABC ipostmenopausal womenn |
|
E.2.2 | Secondary objectives of the trial |
To assess secondary measures of efficacy for PD 0332991 administered in combination;To assess the safety and tolerability of PD 0332991 administered in combination with letrozole and of letrozole alone;To assess the impact of PD 0332991 in combination with letrozole and of letrozole alone on patient reported outcomes of pain severity and pain interference with various activities of daily life using the Modified Brief Pain Inventory Sho To explore the relationship between the baseline tumor levels of Rb, p16/INK4A, CCND1, CDK4/6 and Ki67 markers and tumor response; To explore the relationship between germline polymorphism in CYP19A1 and CCND1 genes and tumor responsert Form (mBPI-sf) questionnaire; |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ALTRI SOTTOSTUDI: Il protocollo prevede un sottostudio di FarmacoGenomica
|
|
E.3 | Principal inclusion criteria |
1. Histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of 1) locally recurrent disease not amenable to resection or radiation therapy with curative intent, or 2) metastatic disease. 2 ER positive tumor. Positivity is defined either as &#8805; 10 fmol of H3 -estrogen binding per mg of cytosol protein for dextran-coated charcoal and sucrose density methods, or &#8805; 0.10 fmol of H3 -estrogen binding per mg of DNA for IF/EIA technique. In case of use of immunohistochemistry, the report should mention positive receptor status according to the standards of the laboratory. 3 HER2 negative breast cancer by FISH or IHC. 4 Paraffin-embedded tumor block(s) available for centralized assessment of Rb and other cell cycle-related proteins. 5 Measurable disease according to RECIST or bone-only disease. Previously irradiated lesions are deemed measurable only if progression is documented at the site after completion of radiation. 6 Females, 18 years of age or older 7 Postmenopausal status defined as: &#61623; Prior bilateral surgical oophorectomy; &#61623; Amenorrhea and age &#8805; 60 years &#61623; Age < 60 years and amenorrhea for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and in the postmenopausal ranges 8 Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1 (see Appendix 1). 9 Resolution of all acute toxic effects of prior therapy or surgical procedures to CTC grade &#8804; 1 (except alopecia or other toxicities not considered a safety risk for the patient). 10 Adequate organ function as defined by the following criteria: &#61623; Absolute neutrophil count (ANC) &#8805; 1500/�L &#61623; Platelets &#8805; 100,000/�L &#61623; Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) &#8804; 3 x upper limit of normal (ULN), or AST and ALT &#8804; 5 x UNL if liver function abnormalities are due to underlying malignancy &#61623; Total serum bilirubin &#8804; 1.5 x UNL regardless of liver involvement secondary to tumor. Inclusion of patients with increased serum indirect bilirubin due to Gilbert�s syndrome is permitted. &#61623; Serum creatinine &#8804; 1.5 x ULN ; QTc &#8804; 470msec; 11 Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment. 12 Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. |
|
E.4 | Principal exclusion criteria |
1. Brain metastases (even if treated and stable), spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. 2. Major surgery within 3 weeks of first study treatment. 3. Prior treatment with: &#61623; Any anti-cancer therapies for advanced disease, with the exception of radiation therapy to < 25% of bone marrow at least 2 weeks prior to study treatment initiation (see Appendix 2) &#61623; (neo)adjuvant letrozole; Any CDK inhibitor. 4. Current treatment with: &#61623; Any anti-cancer therapies for advanced disease &#61623; Any experimental treatment on another clinical trial &#61623; Therapeutic doses of anticoagulant. Low dose anticoagulants for deep vein thrombosis prophylaxis are allowed. Low molecular weight heparin is allowed. Aspirin is permitted. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival |
|
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | No |
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 | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |