A Study of RO5509554 as Monotherapy and in Combination With Paclitaxel in Participants With Advanced Solid Tumors

Roche

Status and phase

Completed

Phase 1

Conditions

Advanced Solid Tumors

Treatments

Drug: RO5509554

Drug: Paclitaxel

Study type

Interventional

Funder types

Industry

Identifiers

NCT01494688

BP27772

2011-003394-28 (EudraCT Number)

Details and patient eligibility

About

This open-label, multicenter, dose-escalation study will assess the safety, tolerability, pharmacokinetics and pharmacodynamics of RO5509554 in participants with advanced solid tumors which are not amenable to standard treatment. In Part I (Dose Escalation), multiple ascending doses of RO5509554 will be administered as monotherapy in participants with solid tumors. Participants with locally advanced and/or metastatic ovarian (including fallopian tube) and breast carcinoma will receive multiple ascending doses of RO5509554 in combination with paclitaxel. In Part II (Expansion Cohort), RO5509554 will be administered as monotherapy to participants with locally advanced and/or metastatic Pigmented Villonodular Synovitis (PVNS)/Tenosynovial Giant Cell Tumor (TGCT), soft tissue sarcoma or malignant mesothelioma, ovarian (including fallopian tube), endometrial or breast cancer and pancreatic cancer. Participants with Human Epidermal Growth Factor Receptor 2 (HER2)/neu negative breast cancer will receive RO5509554 in combination with paclitaxel. Anticipated time on study treatment is until disease progression, unacceptable toxicity, death or participant refusal, whichever occurs first.

Enrollment

217 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically confirmed advanced and/or metastatic solid tumors which are not amenable to standard therapy, with exceptions as defined in exclusion criteria
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Measurable disease according to RECIST criteria version 1.1
Adequate bone marrow, cardiac, liver and renal function

Exclusion criteria

Participants with histologically proven Hepatocellular Carcinoma (HC), Non Small Cell Lung Cancer (NSCLC), Small Cell Lung Cancer (SCLC), gastric cancer, malignant melanoma, nonmetastatic and locally controlled PVNS/TGCT
Participants with known auto-immune disease
Known or suspected central nervous system (CNS) metastases including leptomeningeal metastasis; participants with radiologically stable, asymptomatic previously irradiated lesion are eligible provided participant is greater than or equal to (>/=) 4 weeks beyond completing cranial irradiation and >/= 3 weeks of corticosteroid therapy
Significant, uncontrolled concomitant diseases, including significant cardiovascular or pulmonary disease
Prior chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy for bone pain), any investigational agent or immunotherapy within 28 days of first receipt of study drug
Prior corticosteroids as anti-cancer therapy within minimum of 14 days of first receipt of study drug
Poorly controlled type 1 or type 2 diabetes mellitus
Prior toxicities from chemotherapy or radiotherapy which have not regressed to Grade less than or equal to (</=) 1 severity National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 or later versions
Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection
Pulmonary embolism or any other thrombo-embolic event within 6 months prior to study entry
History of hematological malignancy within the last 5 years prior to study entry
Participant requires high dose corticosteroid treatment ( i.e. greater than (>) 20 mg dexamethasone a day or equivalent for > 7 consecutive days)
Any surgical procedure, including the required baseline tumor biopsy, within less than 14 days of first receipt of study drug. Major surgery within 28 days of first receipt of study drug
Pregnant or lactating women

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

217 participants in 4 patient groups

Part 1 - Dose Escalation: RO5509554

Experimental group

Description:

Participants will receive a single, low dose of 100 milligrams (mg) RO5509554 in 7-day PK run-in period (Cycle 0), followed by dose escalation from Day 1 of Cycle 1. RO5509554 will be escalated as monotherapy in approximately 6 cohorts with dose increments between cohorts of up to 100 percent (%). The doses will be escalated further until MTD/OBD as single agent is reached.

Treatment:

Drug: RO5509554

Part 1 - Dose Escalation: RO5509554 + Paclitaxel

Experimental group

Description:

RO5509554 will be administered in combination with a fixed dose of weekly (QW) paclitaxel (80 milligrams per square meter \[mg/m\^2\]). The starting dose for RO5509554 in combination with paclitaxel will be 2 dose levels below to that of the highest dose of monotherapy RO5509554. Escalation of RO5509554 in combination with QW paclitaxel will start in a standard 3 + 3 design until MTD/OBD as combination dose is reached. If the initial combination is not tolerated, further cohorts will be dosed with the same dose of paclitaxel and lower dose of RO5509554. If insufficient safety, pharmacokinetic or pharmacodynamic data have been collected at the MTD/OBD, up to an additional 4 participants may be enrolled at that dose level.

Treatment:

Drug: Paclitaxel

Drug: RO5509554

Part 2 - Expansion Cohort: RO5509554

Experimental group

Description:

Participants will receive RO5509554 1000 mg Q2W, Q3W or initial biweekly followed by monthly maintenance.

Treatment:

Drug: RO5509554

Part 2 - Expansion Cohort: RO5509554 + Paclitaxel

Experimental group

Description: