A trial investigating the efficacy of TKI258 in patients with cancer of theendometrium that has progressed after prior therapy

• Conditions: Advanced and/or metastatic endometrial carcinoma; MedDRA version: 14.1Level: PTClassification code 10014736Term: Endometrial cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-000266-35-IT
• Lead Sponsor: OVARTIS FARMA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03-13
• Last Update Posted: 30 June 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Female patients aged = 18 years 2. Histologically confirmed diagnosis of advanced and/or metastatic endometrial cancer • Eligible histologies include: endometrioid, uterine papillary serous carcinoma, papillary endometrioid, clear cell, mucinous, adenosquamous, and mixed types (e.g., endometrioid plus serous papillary and/or clear cell) 3. Available tissue specimen, either archival tissue or a fixed fresh biopsy, for assessment of FGFR2 mutation • Confirmation by Novartis-designated laboratory of whether a patient has FGFR2 mutation or is wild-type 4. Documented radiological evidence of progressive disease, as per RECIST v1.1 (Section 14.1), after first-line antineoplastic treatment for advanced and/or metastatic endometrial cancer. One prior line of antineoplastic treatment is defined as: • First-line treatment for metastatic disease including at least one cytotoxic agent • Any neoadjuvant/adjuvant treatment is not considered a prior line of treatment, unless the recurrence occurred while on neoadjuvant/adjuvant chemotherapy or = 6 months since the last administration of neoadjuvant/adjuvant chemotherapy, in which case the neoadjuvant/adjuvant therapy will be considered as one prior regimen of systemic chemotherapy for advanced disease • Any prior hormonal treatment is not considered a line of treatment in any setting 5. Complete recovery from major side effects of prior anticancer radiotherapy and from any drug-related adverse events derived from previous anticancer treatments, excluding alopecia and CTCAE grade 1 peripheral neuropathy 6. Patient has at least one measurable lesion based on RECIST v1.1 (Section 14.1) as determined by the investigator. Lesions in previously irradiated areas should not be selected as target lesions, unless they have clearly progressed since the radiotherapy. 7. ECOG performance status = 2 8. Patients must have the following laboratory values: • Absolute neutrophil count = 1.5 x 109/L • Platelets = 100 x 109/L • Hemoglobin > 9 g/dL • Serum total bilirubin = 1.5 x ULN • ALT and AST = 3.0 x ULN (with or without liver metastases) • Serum creatinine = 1.5 x ULN 9. Written informed consent obtained according to local guidelines
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1. Patients who have received prior anticancer therapy with an FGFR inhibitor 2. Patients who have received > 1 prior line(s) of anticancer treatment for advanced (neoadjuvant/adjuvant therapy not considered one line as per inclusion criterion #4) or metastatic disease 3. Patients with uterine sarcomas, adenosarcoma, and malignant Mullerian tumors 4. Patients with isolated recurrences (vaginal, pelvic, or para-aortic) potentially curative with radiation therapy or surgery 5. Patients with known brain metastases 6. Patients with another primary malignancy within 3 years prior to starting study treatment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix 7. Patients who have participated in a prior anticancer investigational study = 30 days prior to enrollment, or = 5 half-lives of the anticancer investigational product, whichever is longer 8. Patients who have received the last administration of anticancer targeted small molecule therapy (e.g., sunitinib, sorafenib, pazopanib, axitinib, everolimus, temsirolimus, ridaforolimus) = 2 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy 9. Patients who have received the last administration of an anticancer monoclonal antibody, immunotherapy, hormonal therapy, or chemotherapy (except nitrosoureas and mitomycin- C) = 4 weeks prior to starting study drug or who have not recovered from the side effects of such therapy 10. Patients who have received the last administration of nitrosourea or mitomycin-C = 6 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy 11. Patients who have received radiotherapy = 4 weeks prior to starting study drug or who have not recovered from radiotherapy-related toxicities (note: palliative radiotherapy for bone lesions = 2 weeks prior to starting study drug is allowed) 12. Patients who have undergone major surgery (e.g., intra-thoracic, intra-abdominal, or intrapelvic) = 4 weeks prior to starting study drug or who have not recovered from side effects of such surgery 13. Patients with a history of pulmonary embolism or untreated deep venous thrombosis = 6 months prior to starting study drug 14. Impaired cardiac function or clinically significant cardiac diseases, including any of the following: see section 5.3 of protocol. 15. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of TKI258 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection) 16. Cirrhosis, chronic active hepatitis, or chronic persistent hepatitis 17. Known history of HIV infection (HIV testing is not mandatory) 18. Patients who are currently receiving prasugrel, clopidogrel, or full dose anticoagulation treatment with therapeutic doses of warfarin. However, treatment with low doses of warfarin (e.g., =2 mg/day) or locally accepted low doses of acetylsalicylic acid (up to 100 mg daily) to prevent cardiovascular events or strokes is allowed. 19. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol 20. Pregnant or breast-feeding women 21. Women of child-bearing potential, who are

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified