Pilot Study of SBRT and CDX-1127 in Prostate Cancer

NCT02284971 | Terminated Phase 1 DMC

• 1 other identifier: 17456
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the combination of stereotactic body radiation therapy (SBRT) and CDX-1127 in subjects with castration resistant prostate cancer. Subjects will be randomized to one of three arms to receive SBRT prior to, after, or in conjunction with the first dose of CDX-1127.

Conditions

Prostatic Neoplasms; Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Number of adverse events

  Up to day 270

• Immunologic (CD8+ T cell and T regulatory cell (Treg) infiltration)

  • Estimate the effect of SBRT, CDX-1127 and the combination of SBRT and CDX- 1127 on CD8+ T cell and T regulatory cell (Treg) infiltration in prostate tumors.

  Up to day 43

Secondary Outcomes (1)

• Immunologic (lymphocyte composition of blood over time).

  Up to day 270

Study Arms (3)

Arm A: CDX1127 & SBRT Concurrent

EXPERIMENTAL

SBRT will be administered to the primary tumor and/or site of metastatic disease over a period of 5 days (Days 1-5) at a constant dose for 1-4 sites of prostate cancer involvement:30 Gy in 5 fractions of 6 Gy each for prostate gland; 25 Gy in 5 fractions for bone and/or soft tissue metastases). Subjects will receive four doses of CDX-1127(3 mg/kg) (Days 1, 43, 64, 85). The study drug will be administered intravenously over a 90-minute time period and will be followed by a 2-hour observation period. A subject's dose of CDX-1127 will be calculated based on their actual body weight at the time of screening. A subject's dose of CDX-1127 will remain constant at each time point, unless they experience a greater than 10% change in body weight.

Biological: CDX1127; Radiation: SBRT

Arm B: CDX1127 & SBRT Sequential; CDX1127 upfront

EXPERIMENTAL

SBRT will be administered to the primary tumor and/or sites of metastatic disease over a period of 5 days (Days 22-26) at a constant dose for 1-4 sites of prostate cancer involvement:30 Gy in 5 fractions of 6 Gy each for prostate gland; 25 Gy in 5 fractions for bone and/or soft tissue metastases). Subjects will receive four doses of CDX-1127(3 mg/kg) (Days 1, 43, 64, 85). The study drug will be administered intravenously over a 90-minute time period and will be followed by a 2-hour observation period. A subject's dose of CDX-1127 will be calculated based on their actual body weight at the time of screening. A subject's dose of CDX-1127 will remain constant at each time point, unless they experience a greater than 10% change in body weight.

Biological: CDX1127; Radiation: SBRT

Arm C: CDX1127 & SBRT Sequential; SBRT upfront

EXPERIMENTAL

SBRT will be administered to the primary tumor and/or sites of metastatic disease over a period of 5 days (Days 1-5) at a constant dose for 1-4 sites of prostate cancer involvement:30 Gy in 5 fractions of 6 Gy each for prostate gland; 25 Gy in 5 fractions for bone and/or soft tissue metastases). Subjects will receive four doses of CDX-1127(3 mg/kg) (Days 22, 43, 64, 85). The study drug will be administered intravenously over a 90-minute time period and will be followed by a 2-hour observation period. A subject's dose of CDX-1127 will be calculated based on their actual body weight at the time of screening. A subject's dose of CDX-1127 will remain constant at each time point, unless they experience a greater than 10% change in body weight.

Biological: CDX1127; Radiation: SBRT

Interventions

CDX1127 BIOLOGICAL

Also known as: Varlilumab

Arm A: CDX1127 & SBRT Concurrent; Arm B: CDX1127 & SBRT Sequential; CDX1127 upfront; Arm C: CDX1127 & SBRT Sequential; SBRT upfront

SBRT RADIATION

Arm A: CDX1127 & SBRT Concurrent; Arm B: CDX1127 & SBRT Sequential; CDX1127 upfront; Arm C: CDX1127 & SBRT Sequential; SBRT upfront

Eligibility Criteria

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

You may qualify if:

• Males, Age ≥ 18 years.
• Participants must have histologically-proven prostrate adenocarcinoma that is castrate-resistant. Progressive disease is defined by one or more of the following:
• A rise in PSA on two successive determinations at least one week apart and PSA level ≥2ng/ml.
• Soft-tissue progression defined by RECIST 1.1.
• Bone disease progression defined by PCWG2 with two or more new lesions on bone scan.
• Patients must have castrate levels of testosterone (\<50 ng/dl \[1.74 nmol/l\]).
• Patients must have undergone orchiectomy, or have been on LHRH agonists or antagonists, for at least 3 months prior to drug initiation. Patients on LHRH agonists/antagonists must remain on these agents for the duration of the study.
• Clinical metastases must be present and confirmed on imaging studies.
• Participants for whom radiation therapy is recommended for the prostate gland (or prostate bed nodule) and/or bone or soft tissue metastases.
• SBRT may be administered to 1-4 sites and the treatment sites can include prostate gland (or prostate bed nodule for post-prostatectomy patients), bone metastases, and soft tissue metastases. Participants must have at least one site of disease that will be both irradiated with SBRT and biopsied to evaluate immunological outcomes.
• ECOG performance status 0-2.
• Adequate hepatic and renal function.

You may not qualify if:

• Prior malignancies, that will affect the completion and interpretation of the study.
• Patients with active CNS metastases from prostate cancer.
• Patients who are currently receiving systemic cytotoxic chemotherapy, radiation, or other experimental therapy, or who have received this therapy within the preceding 4 weeks. Patients who are currently receiving nitrosoureas or who have received this therapy within the preceding 6 weeks are excluded.
• Patients who are currently receiving systemic cytotoxic chemotherapy, radiation, or other experimental therapy, or who have received this therapy within the preceding 4 weeks.
• Major surgery within 4 weeks prior to the start of study treatment.
• Patients who are receiving or have previously been treated CDX-1127.
• HIV positivity
• Evidence of active Hepatitis B virus or Hepatitis C virus.
• Patients receiving the following medications at study entry or within the preceding 4 weeks (or longer, if otherwise specified) are excluded:
• Checkpoint inhibitors (within the preceding12 weeks)
• Allergy desensitization injections
• Systemic corticosteroids of more than 10 mg per day of prednisone (or equivalent), administered parenterally or orally, except for physiologic replacement. Inhaled steroids (e.g. Advair®, Flovent®, Azmacort®) are not permitted. Topical corticosteroids are acceptable, including steroids with very low solubility administered nasally for local effects only (e.g. Nasonex®)
• Any growth factors (e.g. GM-CSF, G-CSF, erythropoietin).
• Interferon or interleukin therapy
• Other Agents with putative immunomodulating activity. (e.g. sipuleucel-T (Provenge ®))

Sponsors & Collaborators

• James Larner, MD: lead
• Celldex Therapeutics: collaborator

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

varlilumab

Condition Hierarchy (Ancestors)

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

Study Officials

• James Larner, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Radiation Oncology

Study Record Dates

• First Submitted: October 29, 2014
• First Posted: November 6, 2014
• Study Start: November 1, 2014
• Primary Completion: April 7, 2016
• Study Completion: April 7, 2016
• Last Updated: May 17, 2018

Record last verified: 2018-05

Locations

US (1)