An open-label, multicohort, phase II study of MPDL3280A in advanced solid tumors
- Conditions
- Patients affected by solid tumors other than hematologic malignancies, non small cell lung cancer , triple-negative breast cancer, urothelial bladder cancer, renal cell carcinoma, melanoma, and glioblastoma that are advanced and have progressed following at least one line of prior systemic therapy or for which standard or curative therapy does not exist or is not considered appropriate by the investigator.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-000269-30-ES
- Lead Sponsor
- Roche Farma, S.A., que representa en España a F. Hoffmann-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 250
1.Ability to comply with protocol
2.Male or female, 18 years of age or older
3.Histologically- or cytologically-documented solid tumors that are advanced and have progressed following at least one line of prior systemic therapy or for which standard or curative therapy does not exist or is not considered appropriate by the investigator
4.Representative formalin-fixed paraffin-embedded tumor specimens in paraffin blocks or, in exceptional cases, 15 unstained slides, with an associated pathology report, for central testing. Detection of tumor in the provided block needs to be confirmed by the central pathology laboratory prior to study enrollment. Patients with fewer than 15 unstained slides available at baseline (but no fewer than 10) may be eligible following discussion with the Sponsor
Only tissue from core needle, punch or excisional biopsy sample collection will be accepted. For core-needle biopsy specimens, at least three cores should be submitted for evaluation. Fine-needle aspiration, brushing, bone tissue, and lavage samples are not acceptable
Patients who do not have tissue specimens meeting eligibility requirements must undergo a biopsy during the screening period. Acceptable samples include core needle biopsies for deep tumor tissue (minimum three cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions
5.Measurable disease as defined by RECIST, v1.1. (except for prostate cancer and malignant pleural mesothelioma) and disease-specific criteria for patients with prostate cancer (see Appendix 6) and malignant pleural mesothelioma (see Appendix 7)
6.ECOG Performance Status of 0 or 1
7.Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1):
-Absolute neutrophil count (ANC) ? 1500 cells/µL (without granulocyte colony-stimulating factor support within 2 weeks before Cycle 1, Day 1)
-Lymphocyte count ? 500/µL
-White blood cell counts > 2500/?L
-Platelet count ? 100,000/µL (without transfusion within 2 weeks before Cycle 1, Day 1)
-Hemoglobin ? 9.0 g/dL (patients may be transfused or receive erythropoyetic treatment to meet this criterion)
-Serum bilirubin < 1.5 × upper limit of normal (ULN), with the following exception:
Patients with known Gilbert disease who have serum bilirubin level ? 3 × ULN may be enrolled
-Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ? 2.5 × ULN, with the following exceptions:
Patients with liver involvement: AST and/or ALT ? 5 × ULN
Patients with liver or bone metastases: alkaline phosphatase ? 5 × ULN
-Serum creatinine ? 1.5 × ULN
-International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ? 1.5 × ULN. This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low?molecular weight heparin or warfarin) should be on a stable dose
8.Women who are not postmenopausal (? 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative se
1.Hematologic malignancies, NSCLC, triple-negative breast cancer, urothelial bladder cancer, renal cell carcinoma, melanoma, and glioblastoma
2.Malignancies other than disease under study within 5 years prior to Cycle 1 Day 1, with the exception of those with a negligible risk of metastasis or death treated with expected curative
3.Uncontrolled tumor-related pain
4.Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
5.Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
6.Active or untreated CNS metastases as determined by CT or MRI evaluation during screening and prior radiographic assessments
7.Leptomeningeal disease
8.Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for ? 2 weeks prior to Cycle 1, Day 1
9.Any approved anticancer therapy, including chemotherapy, hormonal therapy or radiotherapy, within 3 weeks prior to initiation of study treatment; however, the following are allowed: hormone-replacement therapy or oral contraceptives and palliative radiotherapy for bone metastases > 2 weeks prior to Cycle 1, Day. Acute toxicities from previous therapy that have not resolved to Grade ? 1, except for alopecia
10.Pregnant and lactating women
11.Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease
12.Significant cardiovascular disease, such as New York Heart Association cardiac disease, myocardial infarction within 3 months prior to Cycle 1, Day 1, unstable arrhythmias or unstable angina
13.Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia or severe pneumonia
14.Received oral or IV antibiotics within 2 weeks prior to Cycle 1, Day. Patients receiving prophylactic antibiotics are eligible
15.Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study
16.History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
17.Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the MPDL3280A formulation
18.History of autoimmune disease. Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible
Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible
19.Prior allogeneic bone marrow transplantation or prior solid organ transplantation
20.History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field is permitted
21.Any other diseases, metabolic dysfunction, physical examination
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method