Phase 1 Study of Anti-OX40 in Patients With Advanced Cancer

• ClinicalTrials.gov Identifier: NCT01644968
• Recruitment Status: Completed
• Last Update Posted: June 15, 2017
• Sponsor: Providence Health & Services
• Information provided by (Responsible Party): Providence Health & Services

Tracking Information

• First Submitted Date: July 17, 2012
• First Posted Date: July 19, 2012
• Last Update Posted Date: June 15, 2017
• Actual Study Start Date: November 2003
• Actual Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 18, 2012)

Dose limiting toxicity [ Time Frame: 28 Days ]

A dose limiting toxicity is defined as any grade >=3 hematologic (except lymphopenia) or non-hematologic toxicity (except hypothyroidism or vitiligo) that, in the opinion of the investigator is considered at lease possibly related to the study treatment. If DLT is observed in greater than two patient in any cohort, then the previous cohort will be the maximal tolerated dose.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 18, 2012)

Immune Response [ Time Frame: Pre-study, Days 5, 8, 15, 29, 36, 43, and 57. ]

Blood tests and leukapheresis product will be collected to determine the response to three types of reporter antigens: (1) new antigen (keyhole limpet hemocyanin (KLH)), (2) recall protein antigen (tetanus), and (3) viral antigen (cytomegalovirus (CMV)). Changes in the number of antigens will be used to determine immune response.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 1 Study of Anti-OX40 in Patients With Advanced Cancer
• Official Title: Phase 1 Trial of a Monoclonal Antibody to OX40 in Patients With Advanced Cancer.
• Brief Summary: This study is designed to determine the safety and highest tolerated dose of anti-OX40 in patients with advanced cancer.
• Detailed Description: This study will evaluate the safety and determine the maximal tolerated dose of anti-OX40; evaluated the immune response to the study treatment; measure the pharmacokinetics of anti-OX40; monitor tumor regression, and identify the most biologically active dose of anti-OX40 to induce antigen-specific responses to a variety of immunogens.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Cancer

Intervention

• Drug: Cohort 1 anti-OX40
  0.1 mg/kg anti-OX40 on days 1, 3, and 5
• Drug: Cohort 2 anti-OX40
  .4 mg/kg anti-OX40 on days 1, 3, and 5
• Drug: Cohort 3 anti-OX40
  2.0 mg/kg anti-OX40 on days 1, 3, and 5
• Biological: Tetanus Day 29
  Tetanus toxoid vaccine 0.5ml (5 LF/ml tetanus toxoid)on Day 29
  Other Name: Tetanus Toxoid, Tetanus Toxoid Adsorbed
• Biological: Tetanus Day 1
  Tetanus toxoid vaccine 0.5ml (5 LF/ml tetanus toxoid)on Day 1.
  Other Name: Tetansu Toxoid, Tetanus Toxoid Adsorbed.
• Biological: KLH Day 1
  1 mg KLH in 1 cc diluent subcutaneously on Day 1.
  Other Name: Immucothel.
• Biological: KLH Day 29
  1 mg KLC in 1 cc diluent by subcutaneous injection on Day 29.
  Other Name: Immucothel.

Study Arms

• Experimental: KLH + anti-OX40
  Day 1: KLH + anti-OX40; Day 3: anti-OX40; Day 4: anti-OX40; Day 29: Tetanus vaccine
  Interventions:

  • Drug: Cohort 1 anti-OX40
  • Drug: Cohort 2 anti-OX40
  • Drug: Cohort 3 anti-OX40
  • Biological: Tetanus Day 29
  • Biological: KLH Day 1
• Experimental: Tetanus vaccine + anti-OX40
  Day 1: Tetanus vaccine + anti-OX40; Day 3: anti-OX40; Day 5: anti-OX40; Day 29: KLH
  Interventions:

  • Drug: Cohort 1 anti-OX40
  • Drug: Cohort 2 anti-OX40
  • Drug: Cohort 3 anti-OX40
  • Biological: Tetanus Day 1
  • Biological: KLH Day 29

• Publications *: Curti BD, Kovacsovics-Bankowski M, Morris N, Walker E, Chisholm L, Floyd K, Walker J, Gonzalez I, Meeuwsen T, Fox BA, Moudgil T, Miller W, Haley D, Coffey T, Fisher B, Delanty-Miller L, Rymarchyk N, Kelly T, Crocenzi T, Bernstein E, Sanborn R, Urba WJ, Weinberg AD. OX40 is a potent immune-stimulating target in late-stage cancer patients. Cancer Res. 2013 Dec 15;73(24):7189-7198. doi: 10.1158/0008-5472.CAN-12-4174. Epub 2013 Oct 31.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 18, 2012): 30
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: April 2017
• Actual Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients with uncurable metastatic carcinoma, lymphoma, or sarcoma.
• ECOG performance status 0, 1, 2
• No active bleeding
• No clinical coagulopathy
• Anticipated lifespan greater than 12 weeks

Exclusion Criteria:

• Active residual toxicity from prior therapies
• Active Infection
• HIV positive
• Hepatitis B or C positive
• Pregnant or nursing women
• Requirement for oral steroids
• Brain metastases
• Presence or history of autoimmune disease
• Shellfish or tetanus allergy
• Splenomegaly
• Lymph nodes greater than 10 cm in maximal diameter
• Uncontrolled angina or class II or IV heart failure

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01644968
• Other Study ID Numbers: 03-066A
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Providence Health & Services
• Study Sponsor: Providence Health & Services
• Collaborators: Not Provided

Investigators

• Principal Investigator: Brendan Curti, MD; Providence Health & Services

• PRS Account: Providence Health & Services
• Verification Date: June 2017