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

NCT01494688 | Completed Phase 1

• 2 other identifiers: BP277722011-003394-28
• Study Type: interventional
• Target: 217
• Locations: 2 countries
• Sites: 7

Brief Summary

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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Adverse Events

  Baseline up to 28 days after last dose (approximately 48 months)

• Part 1: Maximum Tolerated Dose (MTD)/Optimal Biological Dose (OBD) of RO5509554 as a Single Agent and in Combination With Paclitaxel

  Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days

Secondary Outcomes (27)

• Part 2: Change in Colony Stimulating Factor-1 (CSF-1) Serum Level For Every 2 Weeks (Q2W) Schedule

  Pre-dose (0 hour [h]), 2, 5, 24, 72 or 96, 168, 216 and 264 h post-dose Cycles 1 & 4; 0 h & any time on Day 8 Cycle 2; 0 h Cycle 3; 0 h Cycle 5 & any time during 28 days follow-up; 0 h Cycle 6 onward up to 48 months [Each cycle=14 days]

• Part 2: Change in CSF-1 Serum Level For Every 3 Weeks (Q3W) Schedule

  Pre-dose (0 h), 3, 24, 72, 168, 264, 312, 432 & 480 h post-dose Cycles 1 & 4; 0 h Cycles 2 & 3; 0 h Cycle 5 & any time during 28 days follow-up; 0 h Cycle 6 onward up to 48 months [Each cycle=21 days]

• Part 2: Change in CSF-1 Serum Level For Initial Q2W Followed by Monthly Maintenance Schedule

  Pre-dose (0 h), 2, 5, 24, 72 or 96, 168, 216 & 264 h post-dose Cycle 1; 0 h & any time on Day 8 Cycle 2; 0 h & 5, 24, 72 or 96, 168, 264, 336, 432, 504 & 576 h post-dose Cycle 3; 0 h Cycle 4 onward up to 48 months [Each cycle=14 or 30 days]

• Change in Circulating Monocytes Subset in Whole Blood For Q2W Schedule

  0,2,5,24,72 or 96,168,216 & 264 h post-dose Cycle 1; 0 h Day 1, any time Day 8 Cycle 2; 0 h Cycles 3 & 5; 0,5,72 or 96,168,216 & 264 h post-dose Cycle 4 & any time during 28 days follow-up; 0 h Cycle 6 onward up to 48 months [Each cycle=14 days]

• Change in Circulating Monocytes Subset in Whole Blood For Q3W Schedule

  0, 3, 24, 72, 168, 264, 312, 432 & 480 h post-dose Cycle 1; 0 h Cycles 2 & 3; 0, 3, 72, 168, 264, 312, 432 & 480 h post-dose Cycle 4; 0 h Cycle 5 & any time during 28 days follow-up; 0 h Cycle 6 onward up to 48 months [Each cycle=21 days]

Study Arms (4)

Part 1 - Dose Escalation: RO5509554

EXPERIMENTAL

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.

Drug: RO5509554

Part 1 - Dose Escalation: RO5509554 + Paclitaxel

EXPERIMENTAL

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.

Drug: Paclitaxel; Drug: RO5509554

Part 2 - Expansion Cohort: RO5509554

EXPERIMENTAL

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

Drug: RO5509554

Part 2 - Expansion Cohort: RO5509554 + Paclitaxel

EXPERIMENTAL

Participants will receive RO5509554 1000 mg Q2W in combination with a fixed dose of QW paclitaxel (80 mg/m\^2).

Drug: Paclitaxel; Drug: RO5509554

Interventions

Paclitaxel DRUG

Paclitaxel, at a dose of 80 mg/m\^2 will be administered QW for up to 12 weeks.

Part 1 - Dose Escalation: RO5509554 + Paclitaxel; Part 2 - Expansion Cohort: RO5509554 + Paclitaxel

RO5509554 DRUG

RO5509554 will be administered Q2W, Q3W or initial biweekly followed by monthly maintenance as intravenous (IV) infusion until disease progression, unacceptable toxicity, death or participant refusal, whichever occurs first.

Also known as: RG7155

Part 1 - Dose Escalation: RO5509554; Part 1 - Dose Escalation: RO5509554 + Paclitaxel; Part 2 - Expansion Cohort: RO5509554; Part 2 - Expansion Cohort: RO5509554 + Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (7)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Univ of Pennsylvania Med Ctr

Philadelphia, Pennsylvania, 19104, United States

Location

Institut Bergonie; Oncologie

Bordeaux, 33076, France

Location

Centre Leon Berard; Departement Oncologie Medicale

Lyon, 69373, France

Location

Institut Curie; Oncologie Medicale

Paris, 75231, France

Location

Ico Rene Gauducheau; Oncologie

Saint-Herblain, 44805, France

Location

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, 31059, France

Location

Related Publications (4)

• Cassier PA, Italiano A, Gomez-Roca C, Le Tourneau C, Toulmonde M, D'Angelo SP, Weber K, Loirat D, Jacob W, Jegg AM, Michielin F, Christen R, Watson C, Cannarile M, Klaman I, Abiraj K, Ries CH, Weisser M, Ruttinger D, Blay JY, Delord JP. Long-term clinical activity, safety and patient-reported quality of life for emactuzumab-treated patients with diffuse-type tenosynovial giant-cell tumour. Eur J Cancer. 2020 Dec;141:162-170. doi: 10.1016/j.ejca.2020.09.038. Epub 2020 Nov 5.

  PMID: 33161240 DERIVED

• Gomez-Roca CA, Italiano A, Le Tourneau C, Cassier PA, Toulmonde M, D'Angelo SP, Campone M, Weber KL, Loirat D, Cannarile MA, Jegg AM, Ries C, Christen R, Meneses-Lorente G, Jacob W, Klaman I, Ooi CH, Watson C, Wonde K, Reis B, Michielin F, Ruttinger D, Delord JP, Blay JY. Phase I study of emactuzumab single agent or in combination with paclitaxel in patients with advanced/metastatic solid tumors reveals depletion of immunosuppressive M2-like macrophages. Ann Oncol. 2019 Aug 1;30(8):1381-1392. doi: 10.1093/annonc/mdz163.

  PMID: 31114846 DERIVED

• Cassier PA, Italiano A, Gomez-Roca CA, Le Tourneau C, Toulmonde M, Cannarile MA, Ries C, Brillouet A, Muller C, Jegg AM, Broske AM, Dembowski M, Bray-French K, Freilinger C, Meneses-Lorente G, Baehner M, Harding R, Ratnayake J, Abiraj K, Gass N, Noh K, Christen RD, Ukarma L, Bompas E, Delord JP, Blay JY, Ruttinger D. CSF1R inhibition with emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: a dose-escalation and dose-expansion phase 1 study. Lancet Oncol. 2015 Aug;16(8):949-56. doi: 10.1016/S1470-2045(15)00132-1. Epub 2015 Jul 12.

  PMID: 26179200 DERIVED

• Ries CH, Cannarile MA, Hoves S, Benz J, Wartha K, Runza V, Rey-Giraud F, Pradel LP, Feuerhake F, Klaman I, Jones T, Jucknischke U, Scheiblich S, Kaluza K, Gorr IH, Walz A, Abiraj K, Cassier PA, Sica A, Gomez-Roca C, de Visser KE, Italiano A, Le Tourneau C, Delord JP, Levitsky H, Blay JY, Ruttinger D. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell. 2014 Jun 16;25(6):846-59. doi: 10.1016/j.ccr.2014.05.016. Epub 2014 Jun 2.

  PMID: 24898549 DERIVED

MeSH Terms

Interventions

Paclitaxel; emactuzumab

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2011
• First Posted: December 19, 2011
• Study Start: December 20, 2011
• Primary Completion: February 7, 2018
• Study Completion: February 7, 2018
• Last Updated: March 16, 2018

Record last verified: 2018-03

Locations

US (2); FR (5)