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

Study Overview
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Brief Summary
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This study is designed to determine the safety and highest tolerated dose of anti-OX40 in patients with advanced cancer.

Detailed Description
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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.

Official Title
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Phase 1 Trial of a Monoclonal Antibody to OX40 in Patients With Advanced Cancer.

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: Cohort 1 anti-OX40
* Drug: Cohort 2 anti-OX40
* Drug: Cohort 3 anti-OX40
* Biological: Tetanus Day 29
* Biological: Tetanus Day 1
* Biological: KLH Day 1
* Biological: KLH Day 29


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KLH + anti-OX40<br>Day 1: KLH + anti-OX40; Day 3: anti-OX40; Day 4: anti-OX40; Day 29: Tetanus vaccine | Drug: Cohort 1 anti-OX40<br>* 0.1 mg/kg anti-OX40 on days 1, 3, and 5<br>Drug: Cohort 2 anti-OX40<br>* .4 mg/kg anti-OX40 on days 1, 3, and 5<br>Drug: Cohort 3 anti-OX40<br>* 2.0 mg/kg anti-OX40 on days 1, 3, and 5<br>Biological: Tetanus Day 29<br>* Tetanus toxoid vaccine 0.5ml (5 LF/ml tetanus toxoid)on Day 29<br>* Other names: Tetanus Toxoid, Tetanus Toxoid Adsorbed;Biological: KLH Day 1<br>* 1 mg KLH in 1 cc diluent subcutaneously on Day 1.<br>* Other names: Immucothel.;|
| Experimental: Tetanus vaccine + anti-OX40<br>Day 1: Tetanus vaccine + anti-OX40; Day 3: anti-OX40; Day 5: anti-OX40; Day 29: KLH | Drug: Cohort 1 anti-OX40<br>* 0.1 mg/kg anti-OX40 on days 1, 3, and 5<br>Drug: Cohort 2 anti-OX40<br>* .4 mg/kg anti-OX40 on days 1, 3, and 5<br>Drug: Cohort 3 anti-OX40<br>* 2.0 mg/kg anti-OX40 on days 1, 3, and 5<br>Biological: Tetanus Day 1<br>* Tetanus toxoid vaccine 0.5ml (5 LF/ml tetanus toxoid)on Day 1.<br>* Other names: Tetansu Toxoid, Tetanus Toxoid Adsorbed.;Biological: KLH Day 29<br>* 1 mg KLC in 1 cc diluent by subcutaneous injection on Day 29.<br>* Other names: Immucothel.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity | 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. | 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune Response | 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. | Pre-study, Days 5, 8, 15, 29, 36, 43, and 57. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic carcinoma, lymphoma, sarcoma, anti-OX40