Anti-OX40, Cyclophosphamide (CTX) and Radiation in Patients With Progressive Metastatic Prostate Cancer

NCT01303705 | Completed Phase 1

• 1 other identifier: PH&S IRB 10-088
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial will examine a novel combination of anti-OX40 to induce proliferation of memory and effector T cells in conjunction with cyclophosphamide (CTX) and radiation to induce tumor antigen release with the overall goal of promoting an immune response against prostate cancer.

Conditions

Metastatic Prostate Cancer; Cancer of the Prostate; Prostate Cancer

Keywords

progressive metastatic prostate cancer; cancer of the prostate; prostate cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  The primary objective of this trial is to determine the maximum tolerated dose (within the range expected to induce anti-tumor and immunological effects) of CTX administered in combination with radiation and anti-OX40 in men with metastatic castrate- and chemotherapy-resistant prostate cancer.

  The MTD will be assessed according to the dose escalation schema (timeframe is not specific for MTD assessment - it is based on enrollment)*

Secondary Outcomes (1)

• Immune and Clinical Responses

  Days 11, 18, 25 and 39

Study Arms (3)

Cyclophosphamide - Cohort 1

EXPERIMENTAL

Cyclophosphamide 300 mg/m2 IV on Day 1; Radiation Therapy 8.0 Gy in 1 fraction to a maximum of three bone metastatic deposits will be administered on Day 4 of treatment; Anti-OX40 will be administered intravenously at 0.4 mg/kg on days 4, 6 and 8.

Drug: Anti-OX40; Radiation: Radiation; Drug: Cyclophosphamide

Cyclophosphamide - Cohort 2

EXPERIMENTAL

Cyclophosphamide 600 mg/m2 IV on Day 1; Radiation Therapy 8.0 Gy in 1 fraction to a maximum of three bone metastatic deposits will be administered on Day 4 of treatment; Anti-OX40 will be administered intravenously at 0.4 mg/kg on days 4, 6 and 8.

Drug: Anti-OX40; Radiation: Radiation; Drug: Cyclophosphamide

Cyclophosphamide - Cohort 3

EXPERIMENTAL

Cyclophosphamide 900 mg/m2 IV on Day 1; Radiation Therapy 8.0 Gy in 1 fraction to a maximum of three bone metastatic deposits will be administered on Day 4 of treatment; Anti-OX40 will be administered intravenously at 0.4 mg/kg on days 4, 6 and 8.

Drug: Anti-OX40; Radiation: Radiation; Drug: Cyclophosphamide

Interventions

Anti-OX40 DRUG

Anti-OX40 will be administered intravenously at 0.4 mg/kg on days 4, 6 and 8 of the study. The total anti-OX40 dose will be reconstituted in 100 ml 0.9% saline and infused over no more than 60 minutes intravenously. A single-use non-pyrogenic durapore membrane low protein binding filter (e.g.: Braun 1.2 micron air eliminating filter or equivalent) shall be used to filter the study product in the line between infusion bag and patient.

Also known as: MEDI6469

Cyclophosphamide - Cohort 1; Cyclophosphamide - Cohort 2; Cyclophosphamide - Cohort 3

Radiation RADIATION

8.0 Gy in 1 fraction to a maximum of three bone metastatic deposits will be administered on Day 4 of treatment. Imaging such as bone scan, MRI, CT scan, or radiograph must identify the target lesion as consistent with metastatic disease. Any bone lesion that is inducing pain or where there may be a clinical concern for potential pathological fracture will be selected over asymptomatic lesions.

Also known as: Rx

Cyclophosphamide - Cohort 1; Cyclophosphamide - Cohort 2; Cyclophosphamide - Cohort 3

Cyclophosphamide DRUG

CTX will be administered on day 1 (Friday only) at a dose determined by cohort assignment. The drug should be diluted per institutional standards. An added dose of IV fluids may help prevent bladder toxicity. In this protocol, CTX will be administered intravenously over 30 - 60 minutes.

Also known as: CTX, Cytoxan

Cyclophosphamide - Cohort 1; Cyclophosphamide - Cohort 2; Cyclophosphamide - Cohort 3

Eligibility Criteria

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

You may qualify if:

• Patients with measurable or evaluable metastatic adenocarcinoma of the prostate. Either histologic or cytologic diagnosis is acceptable
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 (Appendix A.)
• Age 18 years old or above
• Laboratory values (performed within 28 days prior to enrollment) as follows:
• WBC ≥ 2000/microlitre
• Serum creatinine \< 1.5 X upper limit of laboratory normal
• Hgb \> 8g/dl (patients may be transfused to reach this level)
• Platelets \> 100,000 cells/mm3
• Total bilirubin \< 1.5 X upper limit of laboratory normal, unless due to Gilbert's disease
• AST (SGOT) and ALT (SGPT) \< 2.5 X upper limit of laboratory normal
• Alkaline phosphatase \< 2.5 X upper limit of laboratory normal (If alkaline phosphatase \> 2.5 X upper limit of laboratory normal due to bone metastases, then patient is eligible.)
• HIV 1 and 2 antibody Negative
• Hepatitis B surface antigen Negative
• Hepatitis C antibody Negative
• PSA \> 2 ng/ml

You may not qualify if:

• Active infection.
• Active autoimmune disease.
• Previous treatment with mouse monoclonal antibodies
• Need for chronic maintenance oral steroids.
• Active brain metastatic disease. Patients with treated brain metastases with surgery, gamma-knife radiosurgery or radiation and stable for at least 4 weeks and off steroids are eligible.
• Any medical or psychiatric condition that in the opinion of the PI would preclude compliance with study procedures.

Sponsors & Collaborators

• Providence Health & Services: lead
• MedImmune LLC: collaborator

Study Sites (1)

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radiation; Cyclophosphamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• 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: November 9, 2010
• First Posted: February 25, 2011
• Study Start: October 14, 2010
• Primary Completion: July 5, 2016
• Study Completion: July 5, 2016
• Last Updated: August 29, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)