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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01688206
Recruitment Status : Completed
First Posted : September 19, 2012
Last Update Posted : October 5, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief 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.

Condition or disease Intervention/treatment Phase
Neoplasms Biological: Atezolizumab [TECENTRIQ] Biological: Vanucizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 132 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multi-center, Dose Escalation Phase I Study of Single Agent RO5520985 (Vanucizumab), and in Combination With Atezolizumab, Administered as an Intravenous Infusion in Patients With Locally Advanced or Metastatic Solid Tumors
Actual Study Start Date : October 31, 2012
Actual Primary Completion Date : December 2, 2016
Actual Study Completion Date : March 12, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Vanucizumab
Participants will receive escalating doses of vanucizumab and fixed dose of vanucizumab, intravenously every 2 weeks.
Biological: Vanucizumab
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.
Other Name: RO5520985

Experimental: Vanucizumab + Atezolizumab
Participants will receive fixed dose of vanucizumab along with atezolizumab, intravenously every 2 weeks.
Biological: Atezolizumab [TECENTRIQ]
Participants will receive atezolizumab at a fixed dose of 840 mg, intravenously every 2 weeks.
Other Name: RO5541267

Biological: Vanucizumab
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.
Other Name: RO5520985




Primary Outcome Measures :
  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 Outcome Measures :
  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) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01688206


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

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01688206    
Other Study ID Numbers: BP28179
2011-005877-22 ( EudraCT Number )
RG7221 ( Other Identifier: Roche )
First Posted: September 19, 2012    Key Record Dates
Last Update Posted: October 5, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs