Solid Tumors Clinical Trial
Official title:
A Phase Ib Study of the Safety and Pharmacology of Atezolizumab Administered With Cobimetinib in Patients With Locally Advanced or Metastatic Solid Tumors
Verified date | December 2019 |
Source | Hoffmann-La Roche |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This is a Phase Ib, open-label, multicenter study designed to assess the safety, tolerability, and pharmacokinetics of coadministration of intravenous (IV) dosing of atezolizumab (an engineered anti-programmed death-ligand 1 [anti-PD-L1] antibody) and oral dosing of cobimetinib in participants with metastatic or locally advanced cancer for which no standard therapy exists.
Status | Completed |
Enrollment | 153 |
Est. completion date | November 4, 2019 |
Est. primary completion date | November 4, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Solid tumor that is metastatic, locally advanced or recurrent - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Life expectancy greater than or equal to (>/=) 12 weeks - Measurable disease, as defined by RECIST v 1.1 - Adequate hematologic and end organ function - Use of highly effective contraception - Histological tumor tissue specimen - Participants enrolling in the indication-specific expansion cohorts in Stage 2 must consent to tumor biopsies and must have one of the following types of cancer: - Metatastic colorectal cancer - Non-small cell lung cancer - Melanoma Exclusion Criteria: Cancer-Specific Exclusion Criteria: - Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment - Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment - Known active or untreated central nervous system (CNS) metastases - Leptomeningeal disease - Uncontrolled tumor-related pain or uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent (once monthly or more frequently) drainage procedures - Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab General Medical Exclusion Criteria: - Pregnant and lactating women - History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins - Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cell or any component of the atezolizumab formulation - History of autoimmune disease - Participants with prior allogeneic stem cell or solid organ transplantation - Positive test for human immunodeficiency virus (HIV) - Participants with active hepatitis B, hepatitis C, or tuberculosis - Severe infections within 4 weeks prior to Cycle 1 Day 1 - Signs or symptoms of infection within 2 weeks prior to Cycle 1 Day 1 - Received therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1 - Significant cardiovascular disease - Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1 Day 1 or anticipation of need for a major surgical procedure during the course of the study - Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1 Exclusion Criteria Unique to Cobimetinib: - History of prior significant toxicity from another mitogen-activated protein kinase (MEK) pathway inhibitor requiring discontinuation of treatment - Allergy or hypersensitivity to components of the cobimetinib formulations - History of congenital long QT syndrome or corrected QT interval (QTc) greater than (>) 450 milliseconds at screening - Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower, as determined by echocardiogram or Multi Gated Acquisition Scan (MUGA) scan - History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration - History of malabsorption syndrome or other condition that would interfere with enteral absorption Exclusion Criteria Related to Medications: - Prior treatment with clusters of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, systemic immunostimulatory agents, or systemic immunosuppressive medications |
Country | Name | City | State |
---|---|---|---|
Australia | Peter MacCallum Cancer Centre-East Melbourne | Melbourne | Victoria |
Australia | Royal Melbourne Hospital | Parkville | Victoria |
Canada | CHUM Hôpital Notre-Dame | Montreal | Quebec |
Canada | Jewish General Hospital | Montreal | Quebec |
Canada | Princess Margaret Hospital; Department of Med Oncology | Toronto | Ontario |
Germany | Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden | Dresden | |
Germany | Universitaetsklinikum Freiburg | Freiburg | |
Korea, Republic of | Asan Medical Center - Oncology | Seoul | |
Korea, Republic of | Seoul National University Hospital | Seoul | |
Singapore | National University Hospital; Cancer Center | Singapore | |
United States | Texas Oncology, P.A. | Arlington | Texas |
United States | Beth Israel Deaconess Med Ctr; Neurology/MS Center | Boston | Massachusetts |
United States | Massachusets General Hospital Clinical Trial Network and Institute | Boston | Massachusetts |
United States | UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina |
United States | Rocky Mountain Cancer Center - Denver | Denver | Colorado |
United States | SCRI-Tennessee Oncology | Nashville | Tennessee |
United States | Yale University School Of Medicine | New Haven | Connecticut |
United States | Sloan Kettering Cancer Center; Pediatric Hematology/Oncology | New York | New York |
United States | Stanford University Medical Center | Palo Alto | California |
United States | Compass Oncology | Portland | Oregon |
United States | University of Washington Seattle Cancer Care Alliance | Seattle | Washington |
Lead Sponsor | Collaborator |
---|---|
Hoffmann-La Roche |
United States, Australia, Canada, Germany, Korea, Republic of, Singapore,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Phase I: Percentage of Participants With Dose-Limiting Toxicities (DLTs) | Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase | ||
Primary | Phase I: Maximum Tolerated Dose of Cobimetinib | Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase | ||
Primary | Phase I: Recommended Phase II Dose of Cobimetinib when Combined with Atezolizumab | Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase | ||
Secondary | Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Azetolizumab | Pre-infusion (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, 8 (cycle length=42 days for Cycle 1; 28 days for subsequent cycles) and at treatment completion visit (up to approximately 3.5 years) | ||
Secondary | Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs) | Baseline up to approximately 3.5 years | ||
Secondary | Serum Maximum Concentration (Cmax) of Atezolizumab | Pre-infusion (Hour 0) on Day 1 of Cycles 2, 3, 4, 8 (cycle length=28 days) and at treatment completion visit (up to approximately 3.5 years); 30 minutes post-infusion (duration=60 minutes) on Cycle 1 Day 1 (cycle length=42 days) | ||
Secondary | Serum Minimum Concentration (Cmin) of Atezolizumab | Pre-infusion (Hour 0) on Day 1 of Cycles 2, 3, 4, 8 (cycle length=28 days) and at treatment completion visit (up to approximately 3.5 years) | ||
Secondary | Plasma Cmax of Cobimetinib | Pre-dose (Hour 0) and Hours 2, 4, 6 post-dose on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days) | ||
Secondary | Plasma Cmin of Cobimetinib | Pre-dose (Hour 0) on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days) | ||
Secondary | Area Under the Concentration-Time Curve (AUC) of Cobimetinib | Pre-dose (Hour 0) and Hours 2, 4, 6 post-dose on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days) | ||
Secondary | Percentage of Participants With Best Overall Response, as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 of Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until progressive disease [PD] or death due to any cause, whichever occurs first [up to approximately 3.5 years]) | Baseline up to 3.5 years (detailed time frame is provided in the description) | |
Secondary | Percentage of Participants With Objective Response (OR; Confirmed Complete Response or Partial Response) as Assessed by Investigator Using RECIST v1.1 | Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years]) | ||
Secondary | Duration of OR, as Determined by Investigator Using RECIST v1.1 | Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years]) | ||
Secondary | Progression-Free Survival (PFS), as Determined by Investigator Using RECIST v1.1 | Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years]) | ||
Secondary | Overall Survival (OS) | Baseline up to death due to any cause (up to approximately 3.5 years) |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT00750841 -
Study of the Effect of Rifampicin on the Pharmacokinetics (PK) of Multiple Doses of Cediranib in Patients With Solid Tumours
|
Phase 1 | |
Withdrawn |
NCT05419817 -
Pembrolizumab With Sitravatinib in Recurrent Endometrial Cancer and Other Solid Tumors With Deficient Mismatch Repair System
|
Phase 2 | |
Completed |
NCT02828930 -
A Study to Determine the Excretion Balance, Pharmacokinetics, Metabolism and Absolute Oral Bioavailability of a Single Oral Dose of [14C]-Labeled Idasanutlin and an Intravenous Tracer Dose of [13C]-Labeled Idasanutlin in a Single Cohort of Participants With Solid Tumors (Malignancies)
|
Phase 1 | |
Completed |
NCT01197170 -
Hormone Receptor Positive Disease Across Solid Tumor Types: A Phase I Study of Single-Agent Hormone Blockade and Combination Approaches With Targeted Agents to Provide Synergy and Overcome Resistance
|
Phase 1 | |
Terminated |
NCT03225105 -
M3541 in Combination With Radiotherapy in Solid Tumors
|
Phase 1 | |
Completed |
NCT03258515 -
A Study to Investigate the Effect of Single Dose of AZD6094 (600 mg) on Cardiac Repolarization in Healthy Volunteers
|
Phase 1 | |
Completed |
NCT01497925 -
Ph 1 Trial of ADI-PEG 20 Plus Docetaxel in Solid Tumors With Emphasis on Prostate Cancer and Non-Small Cell Lung Cancer
|
Phase 1 | |
Completed |
NCT01878890 -
Phase I Dose Escalation Trial of Efavirenz in Solid Tumours or Non-Hodgkin Lymphoma in Therapeutic Failure.
|
Phase 1 | |
Active, not recruiting |
NCT05059522 -
Continued Access Study for Participants Deriving Benefit in Pfizer-Sponsored Avelumab Parent Studies That Are Closing
|
Phase 3 | |
Active, not recruiting |
NCT03634982 -
Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors
|
Phase 1 | |
Recruiting |
NCT04685226 -
A Phase I/II Clinical Trial of ICP-723 in the Treatment of Advanced Solid Tumors
|
Phase 1/Phase 2 | |
Recruiting |
NCT03175224 -
APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
|
Phase 2 | |
Recruiting |
NCT06036121 -
A Study of ADRX-0706 in Select Advanced Solid Tumors
|
Phase 1 | |
Active, not recruiting |
NCT03258151 -
Association of Genetic Polymorphisms With Docetaxel-based Chemotherapy Toxicities in Chinese Solid Tumor Patients
|
||
Completed |
NCT01528046 -
Metformin in Children With Relapsed or Refractory Solid Tumors
|
Phase 1 | |
Recruiting |
NCT05325866 -
A Study Evaluating Bemarituzumab in Solid Tumors With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression
|
Phase 1/Phase 2 | |
Recruiting |
NCT04557449 -
Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors
|
Phase 1/Phase 2 | |
Completed |
NCT02759640 -
A Phase I Trial of HS-10241 in Solid Tumors
|
Phase 1 | |
Terminated |
NCT02890368 -
Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides
|
Phase 1 | |
Withdrawn |
NCT01940601 -
Pharmacodynamics, Pharmacokinetics, Efficacy and Safety of Balugrastim in Pediatric Patients With Solid Tumors
|
Phase 2 |