| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Platinum-refractory, locally advanced or metastatic non-small cell lung cancer (NSCLC) |
| Pazienti con diagnosi di carcinoma polmonare non a piccole cellule (NSCLC) metastatico o localmente avanzato, refrattari al platino |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061873 |
| E.1.2 | Term | Non-small cell lung cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 compare the progression-free survival (PFS) for SU011248 plus erlotinib versus placebo plus erlotinib in patients with platinum-refractory NSCLC. |
| Confrontare la sopravvivenza libera da progressione (PFS) del SU011248 associato a erlotinib vs placebo associato a erlotinib in pazienti affetti da carcinoma polmonare non a piccole cellule refrattari al platino. |
|
| E.2.2 | Secondary objectives of the trial |
| To compare the objective response rate (ORR) for SU011248 plus erlotinib versus placebo plus erlotinib as treatment for platinum-refractory NSCLC. To evaluate measures of duration of tumor control and compare survival. To compare the safety and tolerability of SU011248 plus erlotinib versus placebo plus erlotinib. To evaluate the plasma pharmacokinetics of erlotinib and SU011248 and its active metabolite SU012662 when these drugs are co-administered. To explore the relationships of cancer biomarkers with cancer- and treatment-related outcomes. To compare patient reported outcomes (PRO) including health-related quality of life (HRQOL) and lung cancer-related symptoms in patients treated with SU011248 plus erlotinib versus placebo plus erlotinib. |
| 1.Confrontare la percentuale di risposta obiettiva (ORR) del SU011248 / erlotinib versus placebo/erlotinib in pazienti affetti da NSCLC refrattari al platino.2.Valutare il controllo della crescita tumorale in termini di durata e comparare la sopravvivenza.3.Confrontare la sicurezza e la tollerabilita` del SU011248 associato all erlotinib vs placebo/ erlotinib.4.Valutare la farmacocinetica nel plasma di erlotinib e SU011248 e del suo metabolita attivo SU012662 quando questi farmaci sono somministrati in associazione.5.Indagare la correlazione dei biomarkers tumorali con il tumore ed I risulatati correlati al trattamento.6.Valutare i cambiamenti nella qualita` di vita correlata allo stato di salute e nella sintomatologia (HRQOL) nei pazienti trattati con SU011248 /erlotinib vs quella dei pazienti trattati con placebo/erlotinib. |
|
| 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 |
PHARMACOGENETIC:
Vers:
Date:
Title:
Objectives:
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FARMACOGENETICA:
Vers:
Data:
Titolo:
Obiettivi:
|
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| E.3 | Principal inclusion criteria |
| 1. Histologically proven diagnosis of NSCLC. 2. Disease that is locally advanced (Stage IIIB with malignant effusion), metastatic (Stage IV), or recurrent (after treatment for Stage IIIB with malignant effusion or Stage IV NSCLC). 3. Prior treatment with 1 or 2 chemotherapy regimens including a platinum-based regimen for advanced disease (Stage IIIB with malignant effusion or Stage IV). 4. Evidence of unidimensionally measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST). 5. Radiographic evidence of disease progression during or following treatment in the advanced disease setting confirmed by the Principal Investigator prior to enrollment in the study. 6. Formalin-fixed, paraffin-embedded tumor tissue available from patients enrolling into the randomized component of this study. (Paired samples collected at the time of the most recent recurrence and at the initial diagnosis are optimal, though samples collected at any time are acceptable). 7. Male or female, 18 years of age or older. Note: Patients enrolled into the lead-in cohort must be <70 years of age. 8. ECOG performance status 0 or 1. 9. Resolution of all acute toxic effects of prior therapy or surgical procedures to grade </=1 (except alopecia). 10. Adequate organ function as defined by the following criteria: - NCI CTCAE severity </= 2 for dyspnea - Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) </=2.5 x upper limit of normal (ULN), or AST and ALT </=5 x ULN if liver function abnormalities are due to underlying malignancy - Total serum bilirubin </=1.5 x ULN - Serum albumin >/=3.0 g/dL - Absolute neutrophil count (ANC) >/=1500/uL - Platelets >/=100,000/L - Hemoglobin >/=9.0 g/dL - Serum creatinine </=1.5 x ULN 11. Signed and dated informed consent document indicating that the patient (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 plans, laboratory tests, and other study procedures. |
| 1. Diagnosi istologicamente confermata di carcinoma polmonare non a piccole cellule. 2. Malattia localmente avanzata (Stadio IIIB con versamento neoplastico), metastatica (Stadio IV), o ricorrente (dopo trattamento per lo Stadio IIIB con versamento neoplastico o Stadio IV ). 3. Precedente trattamento con 1 o 2 regimi chemioterapici incluso un regime contenente platino per la malattia in stadio avanzato (Stadio IIIB con versamento neoplastico o Stadio IV). 4. Evidenza di malattia unidimensionalmente misurabile secondo i Criteri per la Valutazione della Risposta nei Tumori Solidi (RECIST). 5. Evidenza radiografica di progressione di malattia durante o dopo il trattamento per lo stadio avanzato confermata dallo Sperimentatore prima dell¿arruolamento nello studio. 6. Disponibilita` del reperto bioptico dei pazienti che verranno arruolati nella fase randomizzata dello studio. 7. Soggetti di sesso maschile o femminile di eta`>18 anni. 8. Performance status 0 or 1 secondo ECOG. 9. Risoluzione di tutti gli effetti tossici acuti determinati da precedenti terapie sistemiche, o interventi chirurgici a grado</=1 (eccetto l¿alopecia). 10. Adeguata funzionalita` d¿organo come definita dai seguenti criteri: ¿ Severita` della dispnea </= 2 secondo NCI CTCAE. ¿ AST e ALT </=2.5 x ULN, o AST e ALT </=5 x ULN se I valori alterati della funzionalita` epatica siano dovuti alla malattia neoplasica. ¿ Bilirubina totale sierica </=1.5 x ULN ¿ Albumina sierica >/=3.0 g/dL ¿ Conta assoluta dei neutrofili (ANC) >/=1500/uL ¿ Piastrine >/=100,000/L ¿ Emoglobina >/=9.0 g/dl ¿ Creatinina sierica </=1.5 x ULN 11. Consenso informato scritto per testimoniare che il paziente (o il suo rappresentante legale) sia stato informato degli aspetti rilevanti dello studio prima dell¿arruolamento. 12. Disponibilita` e possibilita` ad effettuare visite mediche programmate, esami di laboratorio e a seguire le procedure dello studio. |
|
| E.4 | Principal exclusion criteria |
| 1. Prior treatment with >2 systemic chemotherapy-based regimens for advanced disease (Stage IIIB with malignant effusion or Stage IV). 2. Prior treatment with any receptor tyrosine kinase inhibitors, VEGF inhibitors, or other angiogenic inhibitors (including but not limited to SU011248, erlotinib, gefitinib, or thalidomide). Note: Patients previously treated with bevacizumab or an IGFR inhibitor will be considered eligible for study entry. Note: Patients previously treated with cetuximab will not be considered eligible for study entry. 3. Major surgery, radiation therapy, or systemic therapy within 4 weeks of starting the study treatment. At least 7 days should elapse since minor surgical procedure including placement of an access device or fine needle aspiration. 4. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue. 5. Prior radiation therapy to >25% of the bone marrow. 6. Evidence of hemoptysis <4 weeks of starting study treatment. Patients with blood-tinged or blood-streaked sputum will be permitted on study if the hemoptysis amounts to less than 5 mL of blood per episode and less than 10 mL of blood per 24-hour period in the best estimate of the investigator. 7. History of or known brain metastases, spinal cord compression, carcinomatous meningitis, or new evidence of brain or leptomenengeal disease on screening CT or MRI scan. 8. Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma. 9. Any of the following within the 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolism. 10. Ongoing cardiac dysrhythmias of NCI CTCAE grade >/=2, atrial fibrillation of any grade, or QTc interval >450 msec for males or >470 msec for females. 11. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy). 12. Current treatment with therapeutic doses of coumarin-derivative anticoagulants such as warfarin (however low dose up to 2 mg daily for deep vein thrombosis prophylaxis is allowed during the Phase 2 component of this study but not during the lead-in portion) or anti-vitamin K agents. If currently receiving prophylaxis, PT or INR must be <1.5 times the ULN. 13. Known human immunodeficiency virus (HIV) infection. 14. Current treatment on another therapeutic clinical trial. 15. Pregnancy or breastfeeding. Female patients who are pregnant or nursing, or men and women of reproductive potential who are unwilling or unable to use adequate contraception to prevent pregnancy during the program. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to study entry. 16. Patients with severe dry eye syndrome, Sjogren¿s syndrome, severe exposure keratopathy, bullous keratopathy, aniridia, severe chemical burns, or neutrophilic keratitis, clinically significant gastrointestinal abnormalities including uncontrolled inflammatory disease (e.g. Crohn¿s or ulcerative colitis). 17. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study. |
| 1. Precedente trattamento con >2 regimi di chemioterapia sistemica per la malattia avanzata (Stadio IIIB con versamento neoplastico o Stadio IV). 2. Precedente trattamento con inibitori del recettore della tirosin chinasi, o con inibitori del VEGF, o inibitori dell¿angiogenesi (compresi ma non limitati al SU011248, erlotinib, gefitinib, o alla talidomide). N.B.: I pazienti precedentemente trattati con bevacizumab o con un inibitore del recettore IGF saranno considerati eleggibili. 3. Interventi di chirurgia maggiore, radioterapia, o terapia sistemica entro le 4 settimane dall¿inizio del trattamento in studio. 4. Precedente chemioterapia ad alte dosi che richiede trapianto di cellule staminali. 5. Precedente radioterapia a >25% del midollo osseo. 6. Evidenza di emottisi nelle 4 settimane l¿inizio del trattamento in studio. I pazienti con sputo velato o striato di sangue saranno eleggibili se la quantita` di sangue sara` inferiore a 5 mL per episodio ed inferiore a 10 mL nelle 24 ore secondo la stima dello sperimentatore. 7. Anamnesi di metastasi cerebrali o compressione spinale o meningite carcinomatosa o evidenza allo screening mediante TAC o risonanza magnetica, di malattia cerebrale o leptomeningea 8. Diagnosi di altri tumori maligni negli ultimi 3 anni, eccetto per il basotelioma e del tumore a cellule squamose della pelle o il carcinoma in situ della cervice uterina che siano stati adeguatamente trattati. 9. Angina instabile o grave, infarto del miocardio, bypass coronarico, insufficienza cardiaca congestizia , embolia polmonare, o grave evento cerebrovascolare nei 12 mesi precedenti l¿inizio del trattamento in studio. 10. Aritmie cardiache in corso di grado >/=2 secondo NCI CTCAE, fibrillazione atriale di qualsiasi grado, o intervallo QTc >450 msec per gli uomini o >470 msec per le donne. 11. Ipertensione non controllata da terapia farmacologica (>150/100 mmHg nonostante la terapia medica ottimale). 12. Trattamento in corso con dosi terapeutiche di warfarin (tuttavia sono permesse bassi dosi di warfarin sino a 2 mg al giorno per la profilassi della trombosi venosa profonda durante la seconda fase dello studio, ma non in quella preliminare (lead in ). 13. Infezione HIV documentata. 14. Trattamento in corso in un altro studio clinico. 15. Gravidanza o allattamento. 16. I pazienti con sindrome di occhio asciutto grave, sindrome di Sjögren, esposizione grave cheratopatia, cheratopatia bollosa, aniridia, gravi ustioni chimiche, o cheratite neutrofila, alterazioni gastrointestinali clinicamente significative, inclusi malattia infiammatoria incontrollata (es. Crohn o la colite ulcerosa) 17. Condizioni cliniche gravi acute o croniche o stati psichiatrici o valori di laboratorio alterati che potrebbero aumentare i rischi associati alla partecipazione allo studio o al trattamento in studio o interferire con l¿interpretazione dei risultati dello studio o a giudizio dello sperimentatore rendere il paziente non idoneo a parteciparvi. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression-Free Survival (PFS) |
| Sopravvivenza libera da progressione (PFS) |
|
| 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 | No |
| 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 | 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| SU011248/erlotinib vs placebo/erlotinib |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| 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 | No |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 51 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 51 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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