Roche trials database

Trial information

A Study of RO5479599 Alone or in Combination With Cetuximab or Erlotinib in Patients With Metastatic and/or Locally Advanced Malignant HER3-Positive Solid Tumors

Status:

Recruiting

Protocol number:

BP27771

Sponsor:

Hoffmann-La Roche

Company division:

Pharmaceutical

Official Scientific Title:

Phase Ia/Ib, open-label, multicenter, dose-escalation study followed by an extension phase to evaluate safety, pharmacokinetics and activity of RO5479599, a glycoengineered antibody against HER3, administered either alone (part A) or in combination with Cetuximab (part B) or in combination with Erlotininb (Part C) in patients with metastatic and/or locally advanced malignant HER3-positive solid tumors of ephitelian cell origin

Brief summary:

This multicenter, open-label, 3-Part dose-escalating study will evaluate the safety, pharmacokinetics and efficacy of RO5479599, alone or in combination with cetuximab or Erlotinib, in patients with metastatic and/or locally advanced malignant HER3-positive solid tumors. Cohorts of patients will receive escalating doses of intravenous RO5479599 as monotherapy (Part A) or in combination with cetuximab (Part B) or erlotinib (Part C). Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. In an imaging substudy, patients will receive one or two doses of zirconium-89-labeled RO5479599 in addition to unlabeled RO5479599 to evaluate the in vivo biodistribution and organ pharmacokinetics of RO5479599. Target sample size is 105.

Study phase:

I

Study type:

Interventional; Treatment; Non-randomized; Parallel; Pharmacokinetics/dynamics study

Conditions:

• Neoplasms

Intervention type:

Drug

Intervention name:

RO5479599

Primary outcome:

1. Safety (Part A, including maximum tolerated dose): Incidence of adverse events Time frame: 72 weeks
2. Safety (Part B and C): Incidence of adverse events Time frame: 50 weeks
3. Pharmacokinetics (Parts A, B and C): Area under the concentration - time curve Time frame: 200 weeks
4. IMG Substudy: In vivo biodistribution as determined by positron emission tomography (PET) scan Time frame: up to Day 8

Key secondary outcomes:

1. Part A: Recommended phase II dose (RPTD) in monotherapy Time frame: 72 weeks
2. Part B: Recommended phase II dose in combination with cetuximab Time frame: 36 weeks
3. Part C: Recommended phase II dose in combination with erlotinib Time frame: 36 weeks
4. Objective response rate (ORR), tumor assessments according to RECIST criteria Time frame: 200 weeks
5. Disease control rate (SD) Time frame: 200 weeks
6. Duration of response Time frame: 200 weeks
7. Progression-free survival Time frame: 200 weeks
8. IMG Substudy: Target saturation by RO5479599, defined as decrease in tissue uptake of radioactivity concentration Time frame: up to Day 8

Inclusion criteria:

• Adult patients, >/= 18 years of age
• European Cooperative Oncology Group (ECOG) performance status 0-2
• Histologically confirmed metastatic and/or locally advanced malignant HER3-expressing solid tumors of epithelian origin
• Availability of tissue and willingness to perform fresh pretreatment biopsies
• Patients for whom no standard therapy exists
• All acute toxic effects of any prior radiotherapy, chemotherapy or surgical procedure must have resolved to Grade </= 1, except for alopecia and Grade 2 peripheral neuropathy
• Adequate hematological, renal and liver function
• Patient's with Gilbert's syndrome will be eligible for the study
• Part B extension cohort: In addition to the above inclusion criteria, patients will be eligible if they have metastatic and/or locally advanced non-small cell lung cancer or squamous cell carcinoma of the head and neck or colorectal cancer (wild type with positive EGFR expression)
• Part C extension cohort: In addition to the above inclusion criteria, patients will be eligible only if they have metastatic and/or locally advanced non-small cell lung cancer or pancreatic cancer

Exclusion criteria:

• Known or clinically suspected CNS primary tumors or metastases including leptomeningeal metastases, except for previously treated CNS metastases that are asymptomatic and did not require steroids or enzyme-inducing anticonvulsants in the last 14 days
• Evidence of significant uncontrolled concomitant diseases or disorders
• Active or uncontrolled infections
• Known HIV infection
• Therapy with antibody or immunotherapy concurrently or within 14 days prior to first dose of study drug
• Regular immunosuppressive therapy
• Concurrent high dose of systemic corticosteroids (> 20 mg/day dexamethasone or equivalent for > 7 consecutive days)

Gender:

Males or Females

Age limits:

Min: 18 years Max: N/A (No limit)

Accepts healthy volunteers:

No

Anticipated start date:

December, 2011

Trial registration date:

14.07.2011

Date last updated:

06.05.2013

This trial is being conducted at the following locations:

Denmark

• KØBENHAVN

Netherlands

• AMSTERDAM
• GRONINGEN
• ROTTERDAM
• UTRECHT

Spain

• VALENCIA

SPAIN

• Barcelona, BARCE

Link to trial result