An open-label, multicohort, phase II study of MPDL3280A in advanced solidtumors
- Conditions
- Patients with histologically documented advanced solid tumors thatmeet protocol-defined cohort specifications, have progressed followingat least one line of prior systemic anticancer therapy, or for which there is no alternative therapy known to prolong survival.MedDRA version: 21.1Level: PTClassification code 10066474Term: Thyroid cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10061306Term: Nasopharyngeal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10008229Term: Cervical cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10004655Term: Biliary carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10071114Term: Metastatic gastric adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10061184Term: Germ cell cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10072737Term: Advanced breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1L
- Registration Number
- EUCTR2015-000269-30-IT
- Lead Sponsor
- F. HOFFMANN - LA ROCHE LTD.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 474
1.Ability to comply with protocol
2.Male or female, 18 years of age or older
3.Histologically documented advanced (i.e. stages III or IV) solid tumors that meet protocol-defined cohort specifications, with progressive disease at study entry and at least one prior line of systemic
anticancer therapy or for which there is no alternative therapy known to prolong survival.
4.Representative formalin-fixed paraffin-embedded (FFPE) 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) or disease-specific criteria
for patients with prostate cancer (see Appendix 6) and malignant pleural
mesothelioma (see Appendix 7)
6.Eastern Cooperative Oncology group 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/µL
-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
-Serum albumin level >3.2 g/dl
-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 or creatinine clearance = 30 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation
-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-therapyinduced
amenorrhea) or surgically sterile must have a negative serum
pregnancy test result within 14 days prior to initiation of study drug
9.For female patients of childbearing potential and male patients
1.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
2.Uncontrolled tumor-related pain
3.Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
4.Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
5.History of treated asymptomatic or symptomatic CNS metastasis or presence of CNS metastases as determined by CT scan or MRI evaluation during screening or at prior radiographic assessments
6.Leptomeningeal disease
7. Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated but not clinically stable for = 2 weeks prior to Cycle 1, Day 1
8.Any approved anticancer therapy, including chemotherapy, hormonal therapy or radiotherapy, within 3 weeks prior to initiation of study treatment, with certain exceptions
9.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.Any other diseases, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complication
13.Significant cardiovascular disease within 3 months prior to Cycle 1,Day 1
14.Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
15.Severe infections within 4 weeks prior to Cycle 1, Day 1
16.Received oral or IV antibiotics within 2 weeks prior to Cycle 1, Day
17.Active tuberculosis
18. Positive test for HIV
19.Patients with a positive hepatitis B surface antigen [HBsAg] test at screening or hepatitis C
20.anticipation of need for a major surgical procedure during the course of the study
21.History of autoimmune disease, except treated/stable autoimmune hypothyroidism or controlled type 1 diabetes mellitus on a stable insulin
regimen. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are permitted provided
that they meet certain pre-specified conditions
22.History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
23.Prior allogeneic bone marrow transplantation or prior solid organ transplantation
24.History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan
25.Administration of a live, attenuated vaccine within 4 weeks prior to Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study treatment or within 5 months after the last dose of atezolizumab
26.Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD1, or anti-PDL1 therapeutic antibodies
27.Treatment with systemic immunostimulatory agents or with an investigational agent within 4 weeks or five half-lives of the drug prior to Cycle 1, Day 1
28.Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1,or an
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