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

NCT01689870 | Withdrawn Phase 1

• 1 other identifier: LUD2012-005
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Metastatic Melanoma

Keywords

OX40; Anti-OX40; Ipilimumab; Melanoma

Outcome Measures

Primary Outcomes (2)

• Assess safety and tolerability according to the National Cancer Institute CTCAE v4.0 (Phase 1 and 2)

  Laboratory tests, vital sign measurements, physical exams and patient interviews will be performed to detect new abnormalities and deteriorations of any pre-existing conditions

  Up to 16 weeks

• Assess Tumor Response by the Immune-related Response Criteria (Phase 2)

  Tumor Response by irRC is defined as irPR or irCR over a period of at least 4 weeks

  Baseline, Week 12 & week 16

Secondary Outcomes (2)

• Determine Anti-OX40 serum concentrations

  Baseline, on days 1, 3 & 5 30 minutes after Anti-OX40 end of infusion, and on days 8 and 15

• Assess the biological activity of anti-OX40 in combination with ipilimumab

  Baseline, Day1, day 3, day 5 day8, day 15, day 22 day 43, day 64, day 85 & 113

Study Arms (4)

Phase 1 Cohort 1

EXPERIMENTAL

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; Drug: Ipilimumab

Phase 1 Cohort 2

EXPERIMENTAL

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; Drug: Ipilimumab

Phase 1 Cohort 3

EXPERIMENTAL

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; Drug: Ipilimumab

Phase 2 Cohort 4

EXPERIMENTAL

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; Drug: Ipilimumab

Interventions

Anti-OX40 DRUG

Anti-OX40 will be administered i.v. over 60 minutes only in the first week on Days 1, 3 and 5

Also known as: CD134 mab

Phase 1 Cohort 1; Phase 1 Cohort 2; Phase 1 Cohort 3; Phase 2 Cohort 4

Ipilimumab DRUG

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

Also known as: YERVOY

Phase 1 Cohort 1; Phase 1 Cohort 2; Phase 1 Cohort 3; Phase 2 Cohort 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ludwig Institute for Cancer Research: lead
• AgonOx: collaborator

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jedd Wolchok, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• Brendan D Curti, MD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2012
• First Posted: September 21, 2012
• Study Start: March 1, 2014
• Primary Completion: June 1, 2014
• Study Completion: August 1, 2014
• Last Updated: April 1, 2014

Record last verified: 2014-03