Advanced Solid TumorsPhase 1NCT01494688
A Study of RO5509554 as Monotherapy and in Combination With Paclitaxel in Participants With Advanced Solid Tumors
A Phase 1 study testing Paclitaxel and RO5509554 in people with Advanced Solid Tumors, run by Hoffmann-La Roche at 7 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- Paclitaxel and RO5509554
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 217 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 20 Dec 2011to 7 Feb 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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 locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
France5 sites
Institut Bergonie; Oncologie
Bordeaux, 33076
Centre Leon Berard; Departement Oncologie Medicale
Lyon, 69373
Institut Curie; Oncologie Medicale
Paris, 75231
Ico Rene Gauducheau; Oncologie
Saint-Herblain, 44805
Institut Claudius Regaud; Departement Oncologie Medicale
Toulouse, 31059
United States2 sites
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Univ of Pennsylvania Med Ctr
Philadelphia, Pennsylvania, 19104
About this study
Official title: Open-Label, Multicenter, Dose Escalation Phase Ia/Ib Study With Expansion Phase to Evaluate Safety, Pharmacokinetics and Activity of RO5509554, Administered as an Intravenous Infusion as Monotherapy and in Combination With Paclitaxel in Patients With Advanced Solid Tumors
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
- Being tested
- Paclitaxel, RO5509554
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
Paclitaxel, at a dose of 80 mg/m^2 will be administered QW for up to 12 weeks.
RO5509554Drug
Also called RG7155
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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). Receives: Drug: Paclitaxel; Drug: RO5509554 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Adverse Events
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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]
Change in Circulating Monocytes Subset in Whole Blood For Initial Q2W Followed by Monthly Maintenance Schedule
Measured: 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; 0h & 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]
Pharmacokinetics of RO5509554: Area Under the Plasma concentration-Time Curve (AUC) for Q2W Schedule
Measured: Pre-dose(0 h),end of infusion(EOI)(over 1.5 h)& 3,4,5,6,24,72 or 96,168,216&264 h post-dose Cycle 1;0 h & EOI Cycles 2,3&5; 0 h,EOI &2,3,4,5,6,24,72 or 96,168,216&264 h post-dose at Cycle 4;0 h,EOI Cycle 6 onward up to 48 months [Each cycle=14 days]
Pharmacokinetics of RO5509554: AUC for Q3W Schedule
Measured: Pre-dose (0 h), EOI (over 1.5 h) and 3, 24, 72, 168, 264, 312, 432 and 480 h post-dose Cycles 1 and 4; pre-dose (0 h) and EOI Cycles 2, 3 and 5; pre-dose (0 h), EOI Cycle 6 onwards up to 48 months [Each cycle=21 days]
Pharmacokinetics of RO5509554: AUC for Initial Q2W Followed by Monthly Maintenance Schedule
Measured: Pre-dose(0 h),EOI(over 1.5 h), 3, 5, 24, 72 or 96, 168, 216, 264 h post-dose Cycle 1; 0 h & EOI Cycle 2; 0 h, EOI & 3, 5, 24, 72 or 96, 168, 264, 336, 432, 504, 576 h post-dose Cycle 3; 0 h & EOI Cycle 4 onward up to 48 months [Each cycle=14 or 30 days]
Pharmacokinetics of RO5509554: Maximum Observed Plasma concentration (Cmax) for Q2W Schedule
Measured: Pre-dose(0 h), EOI (over 1.5 h) & 3,4,5,6,24,72 or 96,168,216&264 h post-dose Cycle 1;0 h & EOI Cycles 2,3&5; 0 h,EOI &2,3,4,5,6,24,72 or 96,168,216&264 h post-dose at Cycle 4;0 h,EOI Cycle 6 onward up to 48 months [Each cycle=14 days]
Pharmacokinetics of RO5509554: Cmax for Q3W Schedule
Measured: Pre-dose (0 h), EOI (over 1.5 h) and 3, 24, 72, 168, 264, 312, 432 and 480 h post-dose Cycles 1 and 4; pre-dose (0 h) and EOI Cycles 2, 3 and 5; pre-dose (0 h), EOI Cycle 6 onwards up to 48 months [Each cycle=21 days]
Pharmacokinetics of RO5509554: Cmax for Initial Q2W Followed by Monthly Maintenance Schedule
Measured: Pre-dose(0 h),EOI(over 1.5 h), 3, 5, 24, 72 or 96, 168, 216, 264 h post-dose Cycle 1; 0 h & EOI Cycle 2; 0 h, EOI & 3, 5, 24, 72 or 96, 168, 264, 336, 432, 504, 576 h post-dose Cycle 3; 0 h & EOI Cycle 4 onward up to 48 months [Each cycle=14 or 30 days]
Pharmacokinetics of RO5509554: Half-life (t1/2) for Q2W Schedule
Measured: Pre-dose(0 h), EOI (over 1.5 h) & 3,4,5,6,24,72 or 96,168,216&264 h post-dose Cycle 1;0 h & EOI Cycles 2,3&5; 0 h,EOI &2,3,4,5,6,24,72 or 96,168,216&264 h post-dose at Cycle 4;0 h,EOI Cycle 6 onward up to 48 months [Each cycle=14 days]
Pharmacokinetics of RO5509554: t1/2 for Q3W Schedule
Measured: Pre-dose (0 h), EOI (over 1.5 h) and 3, 24, 72, 168, 264, 312, 432 and 480 h post-dose Cycles 1 and 4; pre-dose (0 h) and EOI Cycles 2, 3 and 5; pre-dose (0 h), EOI Cycle 6 onwards up to 48 months [Each cycle=21 days]
Pharmacokinetics of RO5509554: t1/2 Initial Q2W Followed by Monthly Maintenance Schedule
Measured: Pre-dose(0 h),EOI(over 1.5 h), 3, 5, 24, 72 or 96, 168, 216, 264 h post-dose Cycle 1; 0 h & EOI Cycle 2; 0 h, EOI & 3, 5, 24, 72 or 96, 168, 264, 336, 432, 504, 576 h post-dose Cycle 3; 0 h & EOI Cycle 4 onward up to 48 months [Each cycle=14 or 30 days]
Pharmacokinetics of RO5509554: Systemic Clearance (CL) for Q2W Schedule
Measured: Pre-dose(0 h), EOI (over 1.5 h) & 3,4,5,6,24,72 or 96,168,216&264 h post-dose Cycle 1;0 h & EOI Cycles 2,3&5; 0 h,EOI &2,3,4,5,6,24,72 or 96,168,216&264 h post-dose at Cycle 4;0 h,EOI Cycle 6 onward up to 48 months [Each cycle=14 days]
Pharmacokinetics of RO5509554: CL for Q3W Schedule
Measured: Pre-dose (0 h), EOI (over 1.5 h) and 3, 24, 72, 168, 264, 312, 432 and 480 h post-dose Cycles 1 and 4; pre-dose (0 h) and EOI Cycles 2, 3 and 5; pre-dose (0 h), EOI Cycle 6 onwards up to 48 months [Each cycle=21 days]
Pharmacokinetics of RO5509554: CL for Initial Q2W Followed by Monthly Maintenance Schedule
Measured: Pre-dose(0 h),EOI(over 1.5 h), 3, 5, 24, 72 or 96, 168, 216, 264 h post-dose Cycle 1; 0 h & EOI Cycle 2; 0 h, EOI & 3, 5, 24, 72 or 96, 168, 264, 336, 432, 504, 576 h post-dose Cycle 3; 0 h & EOI Cycle 4 onward up to 48 months [Each cycle=14 or 30 days]
Change in Pharmacodynamic Markers: Dermal Macrophages Expressing CD68/CD163 and Colony Stimulating Factor-1 Receptor (CSF-1R) in Paired Skin Biopsies
Measured: Baseline, Day 1 Cycle 2 pre-dose (0 h), Day 8 Cycle 2 [Each Cycle = 14 or 21 days]
Change in Pharmacodynamic Markers: Dermal Macrophages Expressing CD68/CD163 and CSF-1R in Paired Tumor Biopsies
Measured: Day -21 to -14, pre-dose (0 h) Day 1 Cycle 3 [Each Cycle = 14 or 21 days]
Change in Pharmacodynamic Markers: Tumor associated Macrophages (TAM) expressing Cells in Surrogate/Tumor Tissue (in Paired Tumor Biopsies)
Measured: Day -21 to -14, pre-dose (0 h) Day 1 Cycle 3 [Each Cycle = 14 or 21 days]
Standard Uptake Value of 18F Fluoro-Deoxy-Glucose (FDG), as Assessed Using Positron Emission Tomography (PET) Imaging
Measured: Baseline up to Cycle 3 Days 1 or 7 (Cycle length = 14 or 21 days)
Part 1: Recommended Phase II Dose (RP2D) of RO5509554
Measured: Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days
Percentage of Participants With Objective Response (OR) Assessed According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Measured: From screening to disease progression, death, withdrawal, or end of study; assessed at screening (within 3 weeks before first dose of study drug) then Day 1 of every third cycle (Each Cycle=14 or 21 days) until end of treatment (approximately 48 months)
Percentage of Participants With Clinical Benefit Assessed According to RECIST Version 1.1
Measured: From screening to disease progression, death, withdrawal, or end of study; assessed at screening (within 3 weeks before first dose of study drug) then Day 1 of every third cycle (Each Cycle=14 or 21 days) until end of treatment (approximately 48 months)
Progression Free Survival (PFS) Assessed According to RECIST Version 1.1
Measured: From screening to disease progression, death, withdrawal, or end of study; assessed at screening (within 3 weeks before first dose of study drug) then Day 1 of every third cycle (Each Cycle=14 or 21 days) until end of treatment (approximately 48 months)
Duration of Response Assessed According to RECIST Version 1.1
Measured: From screening to disease progression, death, withdrawal, or end of study; assessed at screening (within 3 weeks before first dose of study drug) then Day 1 of every third cycle (Each Cycle=14 or 21 days)) until end of treatment (approximately 48 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2011 (estimated)
- Study start20 Dec 2011
- Primary completion7 Feb 2018
- Study completion7 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 217 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01494688
- Sponsor's protocol ID
- BP27772
- Other IDs
- 2011-003394-28
- Status last verified
- Mar 2018
- First submitted
- 2 Dec 2011
- Last updated
- 16 Mar 2018
- Results posted
- No
Publications
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.
PubMed 33161240Gomez-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.
PubMed 31114846Cassier 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.
PubMed 26179200Ries 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.
PubMed 24898549
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-Label, Multicenter, Dose Escalation Phase Ia/Ib Study With Expansion Phase to Evaluate Safety, Pharmacokinetics and Activity of RO5509554, Administered as an Intravenous Infusion as Monotherapy and in Combination With Paclitaxel in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01494688
- Acronym / sponsor ID
- BP27772
- Conditions
- Advanced Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 217 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 20 Dec 2011 (actual)
- Primary completion
- 7 Feb 2018 (actual)
- Study completion
- 7 Feb 2018 (actual)
- First posted
- 19 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1 - Dose Escalation: RO5509554 | Experimental | Drug: RO5509554Participants 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. |
| Part 1 - Dose Escalation: RO5509554 + Paclitaxel | Experimental | Drug: Paclitaxel, Drug: RO5509554RO5509554 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. |
| Part 2 - Expansion Cohort: RO5509554 | Experimental | Drug: RO5509554Participants will receive RO5509554 1000 mg Q2W, Q3W or initial biweekly followed by monthly maintenance. |
| Part 2 - Expansion Cohort: RO5509554 + Paclitaxel | Experimental | Drug: Paclitaxel, Drug: RO5509554Participants will receive RO5509554 1000 mg Q2W in combination with a fixed dose of QW paclitaxel (80 mg/m^2). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PaclitaxelPaclitaxel, at a dose of 80 mg/m^2 will be administered QW for up to 12 weeks. | Drug | Part 1 - Dose Escalation: RO5509554 + Paclitaxel, Part 2 - Expansion Cohort: RO5509554 + Paclitaxel |
| RO5509554Also: RG7155RO5509554 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. | Drug | Part 1 - Dose Escalation: RO5509554, Part 1 - Dose Escalation: RO5509554 + Paclitaxel, Part 2 - Expansion Cohort: RO5509554, Part 2 - Expansion Cohort: RO5509554 + Paclitaxel |
Primary outcome
Percentage of Participants With Adverse Events
Time frame: 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
Time frame: Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days
27 secondary outcomes
Part 2: Change in Colony Stimulating Factor-1 (CSF-1) Serum Level For Every 2 Weeks (Q2W) Schedule
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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]
Change in Circulating Monocytes Subset in Whole Blood For Initial Q2W Followed by Monthly Maintenance Schedule
Time frame: 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; 0h & 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]
Pharmacokinetics of RO5509554: Area Under the Plasma concentration-Time Curve (AUC) for Q2W Schedule
Time frame: Pre-dose(0 h),end of infusion(EOI)(over 1.5 h)& 3,4,5,6,24,72 or 96,168,216&264 h post-dose Cycle 1;0 h & EOI Cycles 2,3&5; 0 h,EOI &2,3,4,5,6,24,72 or 96,168,216&264 h post-dose at Cycle 4;0 h,EOI Cycle 6 onward up to 48 months [Each cycle=14 days]
Pharmacokinetics of RO5509554: AUC for Q3W Schedule
Time frame: Pre-dose (0 h), EOI (over 1.5 h) and 3, 24, 72, 168, 264, 312, 432 and 480 h post-dose Cycles 1 and 4; pre-dose (0 h) and EOI Cycles 2, 3 and 5; pre-dose (0 h), EOI Cycle 6 onwards up to 48 months [Each cycle=21 days]
Pharmacokinetics of RO5509554: AUC for Initial Q2W Followed by Monthly Maintenance Schedule
Time frame: Pre-dose(0 h),EOI(over 1.5 h), 3, 5, 24, 72 or 96, 168, 216, 264 h post-dose Cycle 1; 0 h & EOI Cycle 2; 0 h, EOI & 3, 5, 24, 72 or 96, 168, 264, 336, 432, 504, 576 h post-dose Cycle 3; 0 h & EOI Cycle 4 onward up to 48 months [Each cycle=14 or 30 days]
Pharmacokinetics of RO5509554: Maximum Observed Plasma concentration (Cmax) for Q2W Schedule
Time frame: Pre-dose(0 h), EOI (over 1.5 h) & 3,4,5,6,24,72 or 96,168,216&264 h post-dose Cycle 1;0 h & EOI Cycles 2,3&5; 0 h,EOI &2,3,4,5,6,24,72 or 96,168,216&264 h post-dose at Cycle 4;0 h,EOI Cycle 6 onward up to 48 months [Each cycle=14 days]
Pharmacokinetics of RO5509554: Cmax for Q3W Schedule
Time frame: Pre-dose (0 h), EOI (over 1.5 h) and 3, 24, 72, 168, 264, 312, 432 and 480 h post-dose Cycles 1 and 4; pre-dose (0 h) and EOI Cycles 2, 3 and 5; pre-dose (0 h), EOI Cycle 6 onwards up to 48 months [Each cycle=21 days]
Pharmacokinetics of RO5509554: Cmax for Initial Q2W Followed by Monthly Maintenance Schedule
Time frame: Pre-dose(0 h),EOI(over 1.5 h), 3, 5, 24, 72 or 96, 168, 216, 264 h post-dose Cycle 1; 0 h & EOI Cycle 2; 0 h, EOI & 3, 5, 24, 72 or 96, 168, 264, 336, 432, 504, 576 h post-dose Cycle 3; 0 h & EOI Cycle 4 onward up to 48 months [Each cycle=14 or 30 days]
Pharmacokinetics of RO5509554: Half-life (t1/2) for Q2W Schedule
Time frame: Pre-dose(0 h), EOI (over 1.5 h) & 3,4,5,6,24,72 or 96,168,216&264 h post-dose Cycle 1;0 h & EOI Cycles 2,3&5; 0 h,EOI &2,3,4,5,6,24,72 or 96,168,216&264 h post-dose at Cycle 4;0 h,EOI Cycle 6 onward up to 48 months [Each cycle=14 days]
Pharmacokinetics of RO5509554: t1/2 for Q3W Schedule
Time frame: Pre-dose (0 h), EOI (over 1.5 h) and 3, 24, 72, 168, 264, 312, 432 and 480 h post-dose Cycles 1 and 4; pre-dose (0 h) and EOI Cycles 2, 3 and 5; pre-dose (0 h), EOI Cycle 6 onwards up to 48 months [Each cycle=21 days]
Pharmacokinetics of RO5509554: t1/2 Initial Q2W Followed by Monthly Maintenance Schedule
Time frame: Pre-dose(0 h),EOI(over 1.5 h), 3, 5, 24, 72 or 96, 168, 216, 264 h post-dose Cycle 1; 0 h & EOI Cycle 2; 0 h, EOI & 3, 5, 24, 72 or 96, 168, 264, 336, 432, 504, 576 h post-dose Cycle 3; 0 h & EOI Cycle 4 onward up to 48 months [Each cycle=14 or 30 days]
Pharmacokinetics of RO5509554: Systemic Clearance (CL) for Q2W Schedule
Time frame: Pre-dose(0 h), EOI (over 1.5 h) & 3,4,5,6,24,72 or 96,168,216&264 h post-dose Cycle 1;0 h & EOI Cycles 2,3&5; 0 h,EOI &2,3,4,5,6,24,72 or 96,168,216&264 h post-dose at Cycle 4;0 h,EOI Cycle 6 onward up to 48 months [Each cycle=14 days]
Pharmacokinetics of RO5509554: CL for Q3W Schedule
Time frame: Pre-dose (0 h), EOI (over 1.5 h) and 3, 24, 72, 168, 264, 312, 432 and 480 h post-dose Cycles 1 and 4; pre-dose (0 h) and EOI Cycles 2, 3 and 5; pre-dose (0 h), EOI Cycle 6 onwards up to 48 months [Each cycle=21 days]
Pharmacokinetics of RO5509554: CL for Initial Q2W Followed by Monthly Maintenance Schedule
Time frame: Pre-dose(0 h),EOI(over 1.5 h), 3, 5, 24, 72 or 96, 168, 216, 264 h post-dose Cycle 1; 0 h & EOI Cycle 2; 0 h, EOI & 3, 5, 24, 72 or 96, 168, 264, 336, 432, 504, 576 h post-dose Cycle 3; 0 h & EOI Cycle 4 onward up to 48 months [Each cycle=14 or 30 days]
Change in Pharmacodynamic Markers: Dermal Macrophages Expressing CD68/CD163 and Colony Stimulating Factor-1 Receptor (CSF-1R) in Paired Skin Biopsies
Time frame: Baseline, Day 1 Cycle 2 pre-dose (0 h), Day 8 Cycle 2 [Each Cycle = 14 or 21 days]
Change in Pharmacodynamic Markers: Dermal Macrophages Expressing CD68/CD163 and CSF-1R in Paired Tumor Biopsies
Time frame: Day -21 to -14, pre-dose (0 h) Day 1 Cycle 3 [Each Cycle = 14 or 21 days]
Change in Pharmacodynamic Markers: Tumor associated Macrophages (TAM) expressing Cells in Surrogate/Tumor Tissue (in Paired Tumor Biopsies)
Time frame: Day -21 to -14, pre-dose (0 h) Day 1 Cycle 3 [Each Cycle = 14 or 21 days]
Standard Uptake Value of 18F Fluoro-Deoxy-Glucose (FDG), as Assessed Using Positron Emission Tomography (PET) Imaging
Time frame: Baseline up to Cycle 3 Days 1 or 7 (Cycle length = 14 or 21 days)
Part 1: Recommended Phase II Dose (RP2D) of RO5509554
Time frame: Cycle 1 Day 1 (cycle length = 14 or 21 days) up to 28 days
Percentage of Participants With Objective Response (OR) Assessed According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time frame: From screening to disease progression, death, withdrawal, or end of study; assessed at screening (within 3 weeks before first dose of study drug) then Day 1 of every third cycle (Each Cycle=14 or 21 days) until end of treatment (approximately 48 months)
Percentage of Participants With Clinical Benefit Assessed According to RECIST Version 1.1
Time frame: From screening to disease progression, death, withdrawal, or end of study; assessed at screening (within 3 weeks before first dose of study drug) then Day 1 of every third cycle (Each Cycle=14 or 21 days) until end of treatment (approximately 48 months)
Progression Free Survival (PFS) Assessed According to RECIST Version 1.1
Time frame: From screening to disease progression, death, withdrawal, or end of study; assessed at screening (within 3 weeks before first dose of study drug) then Day 1 of every third cycle (Each Cycle=14 or 21 days) until end of treatment (approximately 48 months)
Duration of Response Assessed According to RECIST Version 1.1
Time frame: From screening to disease progression, death, withdrawal, or end of study; assessed at screening (within 3 weeks before first dose of study drug) then Day 1 of every third cycle (Each Cycle=14 or 21 days)) until end of treatment (approximately 48 months)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2018.
- Derived from this study: PubMed 33161240Cassier 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.
- Derived from this study: PubMed 31114846Gomez-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.
- Derived from this study: PubMed 26179200Cassier 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.
- Derived from this study: PubMed 24898549Ries 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Paclitaxel and RO5509554 in people with Advanced Solid Tumors, run by Hoffmann-La Roche at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in France, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Adverse Events (time frame: Baseline up to 28 days after last dose (approximately 48 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01494688, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2018.