A Study to Evaluate Safety, Pharmacokinetics, and Efficacy of RO6895882 in Participants With Advanced and/or Metastatic Solid Tumors

NCT ID: NCT02004106

Last Updated: 2018-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2016-08-31

Brief Summary

This open-label, multi-center, dose-escalation study will evaluate the safety, pharmacokinetics, and therapeutic activity of RO6895882 in participants with Carcinoembryonic Antigen (CEA)-positive solid tumors who have progressed on the standard of care therapy. The study will be conducted in 3 parts. Part 1 will be a single ascending dose study in single participant cohort at low RO6895882 dose (less than or equal to [</=] 6 milligrams [mg]). Part 2 will be a dose-escalation study of RO6895882 monotherapy given every week (qw), every 2 weeks (q2w), and possibly every 3 weeks (q3w). Part 3 will be an expansion phase of the qw, q2w, and possibly q3w at maximum tolerated dose (MTD) (as determined in Part 2). Part 3 will only be conducted if the risk/benefit assessment, as evaluated by the Sponsor and the investigators, is in favor of the participants. Participants will be treated until disease progression, unacceptable toxicity or withdrawal from treatment for other reasons or death for a maximum duration of 24 months.

Conditions

Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: RO6895882 Single Ascending Dose

Participants will receive RO6895882 at ascending doses (\</= 6 mg) as a single intravenous (IV) infusion.

Group Type: EXPERIMENTAL

RO6895882

Intervention Type: DRUG

Participants will receive RO6895882 at different dose levels and schedules defined in respective arms as IV infusion.

Part 2: RO6895882 Dose Escalation Monotherapy

Participants in different cohorts will receive RO6895882 at ascending doses as IV infusion qw, q2w or q3w. After completion of Part 2 all participants have the option to receive the recommended RO6895882 dose once defined in Part 2 at the discretion of investigator.

Group Type: EXPERIMENTAL

RO6895882

Intervention Type: DRUG

Participants will receive RO6895882 at different dose levels and schedules defined in respective arms as IV infusion.

Part 3: RO6895882 MTD Expansion

Participants will receive RO6895882 at MTD determined in Part 2 as IV infusion qw, q2w or q3w.

Group Type: EXPERIMENTAL

RO6895882

Intervention Type: DRUG

Participants will receive RO6895882 at different dose levels and schedules defined in respective arms as IV infusion.

Interventions

RO6895882

Participants will receive RO6895882 at different dose levels and schedules defined in respective arms as IV infusion.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participants with confirmed advanced and/or metastatic solid tumor, with at least one tumor lesion of non-critical location accessible to biopsy who have progressed on the standard of care therapy
• Locally confirmed CEA expression in tumor tissue (more than [>] 20 percent (%) of tumor cells staining with at least moderate intensity) or centrally confirmed CEA expression if no archival tumor tissue and fresh biopsy is collected
• Radiologically measurable and clinically evaluable disease
• Life expectancy of greater than or equal to (>/=) 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• All acute toxic effects of any prior radiotherapy, chemotherapy or surgical procedure must have resolved to Grade </=1, except alopecia (any grade) and Grade 2 peripheral neuropathy
• Adequate hematological, liver, and renal function
• Negative serum pregnancy test within 7 days prior to study treatment in premenopausal women and women </=2 years after menopause
• Participants with Gilbert's syndrome will be eligible for the study. A diagnosis of Gilbert's syndrome will be based on the exclusion of other diseases based on the following criteria: (i) unconjugated hyperbilirubinemia noted on several occasions; (ii) no evidence of hemolysis (normal hemoglobin, reticulocyte count, and Lactate dehydrogenase); (iii) normal liver function tests; (iv) absence of other diseases associated with unconjugated hyperbilirubinemia

Exclusion Criteria

• History or clinical evidence of central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases unless they have been previously treated, are asymptomatic and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days before screening
• Participants with an active second malignancy (other than non-melanoma skin cancer, or cervical carcinoma in situ). Participants who have a history of malignancy are not considered to have an active malignancy if they have completed therapy and are considered by their treating physician to be at less than (<) 30% risk for relapse
• Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders and known autoimmune diseases
• Uncontrolled hypertension (systolic >150 millimeter of mercury [mmHg] and/or diastolic >100 mmHg), unstable angina, congestive heart failure (CHF) of any New York Heart Association (NYHA) classification, serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 6 months of enrollment
• Active or uncontrolled infections
• Known infection with human immunodeficiency virus (HIV), seropositive status
• Positive test results for chronic hepatitis B infection (defined as positive Hepatitis B surface antigen [HBsAg] serology and/or HBcAb status)
• Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing)
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
• Pregnant or breast-feeding women
• Known hypersensitivity to any of the components of RO6895882
• Concurrent therapy with any other investigational drug
• Regular immunosuppressive therapy (that is, for organ transplantation, chronic rheumatologic disease)
• Chronic use of steroids (including inhaled) will not be allowed. Concurrent high doses of systemic corticosteroids. High dose is considered as >20 mg of dexamethasone a day (or equivalent) for >7 consecutive days
• Radiotherapy within the last 4 weeks before start of study drug treatment with the exception of limited field palliative radiotherapy for bone pain relief

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Rigshospitalet, Onkologisk Klinik

København Ø, , Denmark

Helsinki University Central Hospital; Dept of Oncology

Helsinki, , Finland

Institut Gustave Roussy; Departement Oncologie Medicale

Villejuif, , France

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

VU MEDISCH CENTRUM; Dept. of Medical Oncology

Amsterdam, , Netherlands

Clinica Universitaria de Navarra; Servicio de oncología

Pamplona, Navarre, Spain

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, , Spain

CHUV; Departement d'Oncologie

Lausanne, , Switzerland

Oxford University Hospitals NHS Trust - Churchill Hospital

Oxford, , United Kingdom

Countries

United States; Denmark; Finland; France; Netherlands; Spain; Switzerland; United Kingdom

Other Identifiers

2013-003041-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BP28920

Identifier Type: -

Identifier Source: org_study_id