Trial record 3 of 12 for:    Ox40

Study of the Combination of Anti-OX40 and Ipilimumab in Patients With Metastatic Melanoma

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
AgonOx
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier:
NCT01689870
First received: September 18, 2012
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

This is an open label, two-phase study combining a dose escalation Phase 1 with a proof-of-concept Phase 2 in patients with unresectable or metastatic melanoma, for whom treatment with ipilimumab is indicated.

The purpose of the Phase 1 is to determine the Anti-OX40 Maximum Tolerated Dose (MTD) and the secondary objectives are anti-OX40 pharmacokinetics, biological activity and the tumor response assessed by the Immune-related Response Criteria.

The purpose of Phase 2 is to determine tumor response (by irRC) and the secondary objectives are anti-OX40 pharmacokinetics, biological activity and Safety/Tolerability.


Condition Intervention Phase
Metastatic Melanoma
Drug: Anti-OX40
Drug: Ipilimumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1/2 Study of the Combination of a Mouse Monoclonal Antibody to OX40 and Ipilimumab in Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Ludwig Institute for Cancer Research:

Primary Outcome Measures:
  • Assess safety and tolerability according to the National Cancer Institute CTCAE v4.0 (Phase 1 and 2) [ Time Frame: Up to 16 weeks ] [ Designated as safety issue: Yes ]
    Laboratory tests, vital sign measurements, physical exams and patient interviews will be performed to detect new abnormalities and deteriorations of any pre-existing conditions

  • Assess Tumor Response by the Immune-related Response Criteria (Phase 2) [ Time Frame: Baseline, Week 12 & week 16 ] [ Designated as safety issue: No ]
    Tumor Response by irRC is defined as irPR or irCR over a period of at least 4 weeks


Secondary Outcome Measures:
  • Determine Anti-OX40 serum concentrations [ Time Frame: Baseline, on days 1, 3 & 5 30 minutes after Anti-OX40 end of infusion, and on days 8 and 15 ] [ Designated as safety issue: Yes ]
    The serum concentration of Anti-OX40 (CD134) will be determined from its binding to OX40 as measured by ELISA

  • Assess the biological activity of anti-OX40 in combination with ipilimumab [ Time Frame: Baseline, Day1, day 3, day 5 day8, day 15, day 22 day 43, day 64, day 85 & 113 ] [ Designated as safety issue: No ]

    The biological activity of anti-OX40 in combination with ipilimumab will be assessed by:

    • Determining immunologic changes in the tumor microenvironment by characterization of tumor-infiltrating lymphocytes (TILs), assessment of antigen-specific T cell responses and immunohistochemical (IHC) characterization of tumor and peri-tumoral tissue
    • Characterizing circulating T-cell subsets by flow cytometry
    • Assessing antigen specific immune responses by ELISA
    • Characterizing surface markers on lymphocytes and peripheral blood cells by flow cytometry
    • Measuring serum level of soluble factors (cytokine profiling)
    • mRNA/miRNA profiling to analyse gene transcription and/or miRNA expression


Enrollment: 0
Study Start Date: March 2014
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1 Cohort 1
Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1. Anti-OX40 will be administered at 0.1 mg/kg over 60 minutes only in the first week on Days 1, 3 and 5.
Drug: Anti-OX40
Anti-OX40 will be administered i.v. over 60 minutes only in the first week on Days 1, 3 and 5
Other Name: CD134 mab
Drug: Ipilimumab
Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1
Other Name: YERVOY
Experimental: Phase 1 Cohort 2
Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1. Anti-OX40 will be administered at 0.2 mg/kg over 60 minutes only in the first week on Days 1, 3 and 5.
Drug: Anti-OX40
Anti-OX40 will be administered i.v. over 60 minutes only in the first week on Days 1, 3 and 5
Other Name: CD134 mab
Drug: Ipilimumab
Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1
Other Name: YERVOY
Experimental: Phase 1 Cohort 3
Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1. Anti-OX40 will be administered at 0.4 mg/kg over 60 minutes only in the first week on Days 1, 3 and 5.
Drug: Anti-OX40
Anti-OX40 will be administered i.v. over 60 minutes only in the first week on Days 1, 3 and 5
Other Name: CD134 mab
Drug: Ipilimumab
Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1
Other Name: YERVOY
Experimental: Phase 2 Cohort 4
Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1. Anti-OX40 will be administered i.v. at the Phase 1 Maximum Tolerated Dose over 60 minutes only in the first week on Days 1, 3 and 5.
Drug: Anti-OX40
Anti-OX40 will be administered i.v. over 60 minutes only in the first week on Days 1, 3 and 5
Other Name: CD134 mab
Drug: Ipilimumab
Ipilimumab will be administered at 3 mg/kg i.v. over 90 minutes every 3 weeks for a total of 4 doses, starting on Day 1
Other Name: YERVOY

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with unresectable or metastatic melanoma, for whom treatment with Ipilimumab is indicated
  • Radiologically measurable disease by immune-related Response Criteria
  • ECOG performance status of 0-1.
  • Anticipated lifespan greater than 12 weeks.
  • At the time of day 1 of the study, patients must be at least 3 weeks since surgery
  • At the time of day 1 of the study, patients with brain metastases must be asymptomatic and, at least 8 weeks without tumor progression after any whole brain radiotherapy, at least 4 weeks since craniotomy and resection or stereotactic radiosurgery, at least 3 weeks without new brain metastases as evidenced by MRI/CT
  • The following laboratory parameters must be within the ranges specified: Hemoglobin-≥ 9 g/dL, WBC-≥ 3.0 x 109/L, INR-≤ 1.5, Total Bilirubin-≤ 1.9 g/dL & AST/ALT-≤ 3 x ULN
  • Have been informed of other treatment options.
  • At least 18 years. Able and willing to give valid written informed consent.

Exclusion Criteria:

  • Any contraindications for ipilimumab/Yervoy®.
  • Prior exposure to ipilimumab/Yervoy®
  • Prior exposure to Anti-OX40 or a mouse monoclonal antibody.
  • History of severe allergic reactions to any unknown allergens or anti-OX40 Autoimmune disease except for autoimmune thyroiditis or vitiligo.
  • Unresolved immune related adverse events following prior biological therapy.
  • Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available.
  • Known immunodeficiency or HIV, Hepatitis B or Hepatitis C positivity.
  • Other serious illnesses (e.g., serious infections requiring antibiotics).
  • Participation in any other clinical trial involving another investigational agent within 4 weeks prior to day 1 of the study.
  • Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
  • Lack of availability for immunological and clinical follow-up assessments.
  • Women who are breast feeding or pregnant as evidenced by positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) done within 72 hours of first dosing.
  • Women of childbearing potential not using a medically acceptable means of contraception for the duration of the study.
  • Any condition that, in the clinical judgment of the treating physician, is likely to prevent the patient from complying with any aspect of the protocol or that may put the patient at unacceptable risk.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01689870

Sponsors and Collaborators
Ludwig Institute for Cancer Research
AgonOx
Investigators
Principal Investigator: Jedd Wolchok, MD, PhD Memorial Sloan-Kettering Cancer Center
Principal Investigator: Brendan D Curti, MD Providence Health & Services
  More Information

No publications provided

Responsible Party: Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier: NCT01689870     History of Changes
Other Study ID Numbers: LUD2012-005
Study First Received: September 18, 2012
Last Updated: March 31, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Ludwig Institute for Cancer Research:
OX40
Anti-OX40
Ipilimumab
Melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014