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CompletedNCT01688206Updated Oct 5, 2018

A Study of Vanucizumab (RO5520985) Alone or in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors

A Phase 1 interventional study of Atezolizumab [TECENTRIQ] and Vanucizumab in Neoplasms, sponsored by Hoffmann-La Roche. Completed at 14 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-10-05.

Sponsored by Hoffmann-La Roche · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
132
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

This multi-center, open-label study will evaluate the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of vanucizumab as a single agent or in combination with atezolizumab in participants with locally advanced or metastatic solid tumors. Cohorts of participants will receive escalating doses of vanucizumab, fixed dose of vanucizumab (MTD and/or recommended phase two dose [RP2D]), and fixed dose of vanucizumab in combination with atezolizumab, intravenously every 2 weeks.

02

Conditions studied

  • Neoplasms
03

In context

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Participants with histologically confirmed epithelial ovarian, fallopian tube or primary peritoneal cancer
  • Participants must have platinum resistant disease defined as progression within \<6 months from completion of a minimum of 4 platinum therapy cycles OR Participants must have platinum refractory disease, which is defined as progression during platinum based chemotherapy
  • Less than or equal to (\<=) 2 prior lines of systemic therapy
  • The participant is willing to consent to and undergo a pre-treatment and on treatment core or excisional biopsy of the tumor
  • Measurable disease as determined by RECIST 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Adequate hematological function
  • Adequate liver function
  • Adequate renal function
  • Adequate coagulation
  • Adequate cardiovascular function
  • Recovery from all reversible adverse events of previous anti-cancer therapies to baseline or Common Terminology Criteria for Adverse Events (CTCAE) Grade (G) 1, except for alopecia (any grade) and \<= G 2 sensory peripheral neuropathy

Exclusion criteria

Exclusion Criteria:

  • Participants with primary central nervous system (CNS) tumors or CNS tumor involvement. Participants with metastatic CNS tumors may participate in this trial under conditions defined by protocol
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1, or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to Day 1 of Cycle 1 or anticipation of the need for major surgical procedure during the course of the study or non-recovery from side effects of any such procedure
  • Significant cardiovascular/cerebrovascular disease within 6 months prior to study drug administration
  • Known human immuno deficiency virus (HIV) infection or known active hepatitis B or hepatitis C virus infection or active tuberculosis
  • Participants previously treated with vascular endothelial growth factor (VEGF)-A inhibitors and with agents targeting Angiopoietin (Ang)-1/2 and/or Tyrosine-protein kinase receptor2
  • History of intra-abdominal inflammatory process within the last 12 months such as, but not limited to, diverticulitis, peptic ulcer disease, or colitis
  • Any prior radiotherapy to the pelvis or abdomen
  • Treatment with systemic immunostimulatory agents, including but not limited to, interferon (IFN)-alpha, IFN-beta, interleukin (IL)-2, conjugated IL-2 cytokines within 6 weeks or five half-lives of the drug, whichever is longer, prior to screening
  • History of bowel obstruction and/or clinical signs or symptoms of gastro-intestinal obstruction, including sub-occlusive disease related to the underlying disease (however, participants with signs/symptoms of sub/occlusive syndrome/bowel obstruction at the time of initial diagnosis may be enrolled if they had received definitive [surgical] treatment for symptom resolution). History of abdominal fistula or tracheo-oesophageal fistula, gastrointestinal perforation or intra-abdominal abscess, unless occurred and resolved before initial diagnosis and unrelated to the underlying cancer disease. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on Computed tomography (CT)
  • Chronic daily treatment with non-steroidal anti-inflammatory drug (NSAID) (occasional use for the symptomatic relief of medical conditions, for example, headache, fever is allowed)
  • Treatment with systemic immunosuppressive medications including, but not limited, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to study drug administration
  • Previous treatment with checkpoint inhibitors (e.g. anti Programmed death [PD]-1, anti-PD-ligand 1, anti Cytotoxic T-lymphocyte-associated molecule-4) or prior treatment with cluster of differentiation (CD) 137 agonists or any other antibody or drug targeting T cell co-stimulation or other immune checkpoint blockade therapies
  • History of autoimmune disease including, but not limited to systemic lupus erythematosus (SLE), Sjögren's syndrome, glomerulonephritis, multiple sclerosis, rheumatoid arthritis, vasculitis, systemic immune activation, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Guillain-Barré syndrome, Bell's palsy
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
  • Prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle1 Day1 or anticipation that such a live attenuated vaccine will be required during the study
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
132 participants (actual)

Study arms

  • Experimental
    Vanucizumab

    Participants will receive escalating doses of vanucizumab and fixed dose of vanucizumab, intravenously every 2 weeks.

    Biological: Vanucizumab

  • Experimental
    Vanucizumab + Atezolizumab

    Participants will receive fixed dose of vanucizumab along with atezolizumab, intravenously every 2 weeks.

    Biological: Atezolizumab [TECENTRIQ] · Biological: Vanucizumab

Interventions

  • BiologicalAtezolizumab [TECENTRIQ]

    Participants will receive atezolizumab at a fixed dose of 840 mg, intravenously every 2 weeks.

    Also known as: RO5541267

  • BiologicalVanucizumab

    Participants will receive escalating doses of vanucizumab (starting dose: 3 milligram \[mg\] per kilogram) and fixed dose of vanucizumab (MTD/RP2D: 30 mg/kg), intravenously every 2 weeks.

    Also known as: RO5520985

06

What researchers measure

Primary outcomes

  1. Maximum Tolerated Dose (MTD) of Vanucizumab

    Time frame: approximately 28 days

  2. Number of Participants With Objective Response According to RECIST 1.1 Criteria

    Time frame: approximately 3 years

  3. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time frame: approximately 3 years

  4. Number of Participants With Dose-limiting Toxicities (DLTs)

    Time frame: approximately 28 days

Secondary outcomes

  1. Elimination Half-life (t1/2) of Vanucizumab

    Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)

  2. Area Under the Plasma Concentration-time Curve During one Dosing Interval (AUCtau) of Vanucizumab

    Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)

  3. Clearance of Study Drug From the Body (CL)

    Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)

  4. Volume of Distribution at Steady-State (Vss) of Vanucizumab

    Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)

  5. Accumulation Ratio (RA) of Vanucizumab

    Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)

  6. Number of Participants With Objective Response According to RECIST 1.1 Criteria, CA-125 Response Criteria, and Immune-modified RECIST Criteria

    Time frame: approximately 3 years

  7. Number of Participants With Disease Control According to RECIST 1.1 Criteria

    Time frame: approximately 3 years

  8. Progression Free Survival (PFS) According to RECIST 1.1 Criteria

    Time frame: Baseline until disease progression or death (up to approximately 3 years)

  9. Biological Progression-free Interval (PFIbio) According to RECIST 1.1 Criteria

    Time frame: Baseline until biologic progression or death (up to approximately 3 years)

  10. Overall Survival (OS)

    Time frame: Baseline until death (up to approximately 3 years)

  11. Change From Baseline in Micro Vessel Density (MVD) Assessed by Paired Tumor Biopsies

    Time frame: approximately 2 years

  12. Change From Baseline in Proliferation and Apoptosis of Endothelial cells and Tumor Cells Assessed by Paired Tumor Biopsies

    Time frame: approximately 2 years

  13. Change From Baseline in Maturity of Blood Vessels Assessed by Paired Tumor Biopsies

    Time frame: approximately 2 years

  14. Change From Baseline in Targets and Receptors Assessed by Paired Tumor Biopsies

    Time frame: approximately 2 years

  15. Change From Baseline in Blood Plasma Volume (Vp), Extracellular Extravascular Space Volume (Ve), and Volume Transfer Coefficient, Assessed by Bio-Imaging

    Time frame: approximately 2 years

  16. Change From Baseline in Apparent Diffusion Coefficient (ADC) Assessed by Bio-Imaging

    Time frame: approximately 2 years

  17. Percentage of Participants With Human Anti-Human Antibodies (HAHA) to Vanucizumab and Atezolizumab (ATA)

    Time frame: 0 hours (pre-dose) in Part I, II, and III (Cycle 1, 5, 6, end of study [EoS] visit) Part IV (Cycle 1, 3, 4, 8, every 8 weeks after cycle 8, EoS visit)

  18. Area under the Concentration-time Curve (AUC) of Vanucizumab

    Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)

  19. Maximum Observed Plasma Concentration (Cmax) of Vanucizumab

    Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)

  20. Minimum Observed Plasma Concentration (Cmin) of Vanucizumab

    Time frame: Cycle 1 & 4: 0 hour (pre-dose); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)

  21. Time of Observed Maximum Plasma Concentration (Tmax)

    Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)

07

Study locations

14 sites
  • Cliniques Universitaires St-Luc
    Bruxelles, 1200, Belgium
  • UZ Leuven Gasthuisberg
    Leuven, 3000, Belgium
  • Institut Bergonie; Oncologie
    Bordeaux, 33076, France
  • Centre Francois Baclesse; Oncologie
    Caen, 14076, France
  • Centre Leon Berard; Departement Oncologie Medicale
    Lyon, 69373, France
  • Institut Curie; Oncologie Medicale
    Paris, 75231, France
  • ICO - Site René Gauducheau
    Saint Herblain, 44805, France
  • Institut Gustave Roussy; Sitep
    VILLEJUIF Cedex, 94805, France
  • Clinica Universitaria de Navarra; Servicio de Oncologia
    Pamplona, Navarra 31008, Spain
  • Hospital del Mar; Servicio de Oncologia
    Barcelona, 08003, Spain
  • Hospital Univ Vall d'Hebron; Servicio de Oncologia
    Barcelona, 08035, Spain
  • Hospital Universitario 12 de Octubre; Servicio de Oncologia
    Madrid, 28041, Spain
  • Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
    Madrid, 28050, Spain
  • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
    Valencia, 46010, Spain
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 5, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT01688206
Lead sponsor
Hoffmann-La Roche
Responsible party
Sponsor
First posted
Sep 19, 2012
Start date
Oct 31, 2012
Primary completion
Dec 2, 2016
Completion
Mar 12, 2018
Last update
Oct 5, 2018

Study contacts

Clinical Trials
study director · Hoffmann-La Roche

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Oct 2018. You cannot join it, but the record below documents what was studied.

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