Source: https://www.smartpatients.com/trials/NCT01494688
Timestamp: 2016-12-06 21:54:45
Document Index: 519738253

Matched Legal Cases: ['art 1', 'art 1', 'art 2', 'art 2', 'art 1', 'art 2', 'art 2', 'art 2', 'art 1']

A Study of RO5509554 as Monotherapy and in Combination With Paclitaxel in Participants With Advanced Solid Tumors | Smart Patients
paclitaxel, ro5509554
NCT01494688, 2011-003394-28, BP27772
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.
Part 1 - Dose Escalation: RO5509554
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.
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.
Part 1 - Dose Escalation: RO5509554 + Paclitaxel
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.
Paclitaxel, at a dose of 80 mg/m^2 will be administered QW for up to 12 weeks.
Part 2 - Expansion Cohort: RO5509554
Participants will receive RO5509554 1000 mg Q2W, Q3W or initial biweekly followed by monthly maintenance.
Part 2 - Expansion Cohort: RO5509554 + Paclitaxel
Participants will receive RO5509554 1000 mg Q2W in combination with a fixed dose of QW paclitaxel (80 mg/m^2).
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
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]
Change in Circulating Monocytes Subset in Whole Blood 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; 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
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
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
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
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
Pharmacokinetics of RO5509554: Cmax for Initial Q2W Followed by Monthly Maintenance Schedule
Pharmacokinetics of RO5509554: Half-life (t1/2) for Q2W Schedule
Pharmacokinetics of RO5509554: t1/2 for Q3W Schedule
Pharmacokinetics of RO5509554: t1/2 Initial Q2W Followed by Monthly Maintenance Schedule
Pharmacokinetics of RO5509554: Systemic Clearance (CL) for Q2W Schedule
Pharmacokinetics of RO5509554: CL for Q3W Schedule
Pharmacokinetics of RO5509554: CL for Initial Q2W Followed by Monthly Maintenance Schedule
Change in Pharmacodynamic Markers: Dermal Macrophages Expressing CD68/CD163 and Colony Stimulating Factor-1 Receptor (CSF-1R) in Paired Skin Biopsies
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
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)
Standard Uptake Value of 18F Fluoro-Deoxy-Glucose (FDG), as Assessed Using Positron Emission Tomography (PET) Imaging
Baseline up to Cycle 3 Days 1 or 7 (Cycle length = 14 or 21 days)
Part 1: Recommended Phase II Dose (RP2D) of RO5509554
Percentage of Participants With Objective Response (OR) Assessed According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
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
Progression Free Survival (PFS) Assessed According to RECIST Version 1.1
Duration of Response Assessed According to RECIST Version 1.1
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)
- 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
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
- Prior corticosteroids as anti-cancer therapy within minimum of 14 days of first
- Poorly controlled type 1 or type 2 diabetes mellitus
less than or equal to () 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
Humanized IgG1 mAb targeting colony-stimulating factor 1 receptor (CSF1R; C-FMS; CD115)