Provenge Followed by Docetaxel in Castration-Resistant Prostate Cancer

NCT02793219 | Withdrawn Phase 2 DMC

• 2 other identifiers: GU-15-103HSC-MS-15-0882
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical study will evaluate the role of combination therapy of Provenge followed by docetaxel for patients with metastatic castration-resistant prostate cancer (CRPC, (prostate cancer that is resistant to medical or surgical treatments that lower testosterone). The purpose of this study is to look at the combination therapy of Provenge followed by docetaxel to correlate the immunological biomarkers with clinical results for therapy. Biomarkers are genes, proteins and other molecules that affect how cancer cells grow, multiply, die and respond to other compounds in the body. The study drugs are approved by the Food and Drug Administration (FDA). Treatment will be administered on an outpatient basis. Patients will receive Provenge followed by 6 cycles of docetaxel. Provenge is an immunotherapy (vaccine made from patient's own blood cells) that reprograms immune cells to attack cancer. A course of therapy consists of three doses of Provenge administered at 2-week intervals. Docetaxel is an antineoplastic (chemotherapy that affects cancer cell growth) agent. Docetaxel dose of 75 mg/m2 will be given intravenously as a 1-hour infusion every 21 days on Day 1 for 6 cycles (21 days). The strategy aims to determine whether cytokine production and T cell infiltration of tumor cells could favor regression using a combination of vaccine plus chemotherapy. Tissue endpoints will include biopsies prior to vaccine therapy and chemotherapy and at the end of therapy. Prostate cancer tissue infiltrates will be studied for expression of CD3, CD4, CD8, CD25/FOX3P, CD56, CTLA-4, PD-1, and Ki67. Additional immunological endpoints will be secondary antigen spread and various cytokine biomarkers.

Conditions

Prostate Cancer

Keywords

Advanced Prostate Cancer; Castration-Resistant Prostate Cancer; CRPC; Adenocarcinoma of the prostate; Metastatic disease

Outcome Measures

Primary Outcomes (5)

• Cytokine Activity

  measured by staining assays

  18 months

• T-cell Proliferation

  measured by flow cytometry

  18 months

• Levels of Serum

  measured by staining assays

  18 months

• Tissue Infiltration

  measured by staining assays

  18 months

• Secondary Antigen Spread

  measured by flow cytometry

  18 months

Secondary Outcomes (6)

• Radiographic progression-free survival

  18 months

• PSA response rate

  18 months

• Time to PSA progression

  18 months

• Measure CTCs and characterize response

  18 months

• Objective tumor response rate

  18 months

Study Arms (1)

Sipuleucel-T then Docetaxel

EXPERIMENTAL

Sipuleucel-T IV over 1-hour every 14 days for 3 doses; 28 day rest; 75 mg/m2 docetaxel IV over 1-hour every 21 days for 6 cycles

Biological: Sipuleucel-T; Drug: Docetaxel

Interventions

Sipuleucel-T BIOLOGICAL

Also known as: Provenge

Sipuleucel-T then Docetaxel

Docetaxel DRUG

Also known as: Taxotere, Docefrez

Sipuleucel-T then Docetaxel

Eligibility Criteria

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

You may qualify if:

• Male 18 years and older.
• Pathologic confirmation of prostate adenocarcinoma.
• Asymptomatic or minimally symptomatic disease.
• Presence of skeletal or visceral/nodal metastasis confirmed by MRI, scintigraphy, or CT scan
• Disease progression as indicated by:
• PSA increase indicated by two consecutive higher values over baseline at assessments performed at least 7 days apart from each other in the previous 28 days with the absolute value ≥5 ng/ml; OR
• Progression of measurable lymph nodes (≥15 mm) measureable per RECIST v1.1 criteria; OR
• New bone lesions appearing on imaging compared with a prior bone scan. (Bone scan to be performed at screening or within the previous 28 days.)
• Maintenance of castrate conditions: Patients who have not had a surgical orchiectomy must continue with hormone therapy (GnRH/LHRH agonists or antagonists) to maintain levels of serum testosterone of \<50 ng/dl.
• Patient is clinically immunocompetent. Clinical immunocompetence will be assumed unless a subject has been diagnosed as being immunosuppressed, is receiving oral steroids (nasal sprays and inhalers are permitted), or is receiving immunosuppressive therapy following transplant, in which case they will be excluded.
• Peripheral neuropathy grade ≤1.
• Laboratory criteria:
• Adequate bone marrow function:
• White blood cells ≥4000/mm3
• Absolute neutrophil count ≥1500/mm3

You may not qualify if:

• Patient's disease burden is greater than the prognostic criteria defined earlier, including the presence of visceral or bone metastases.
• Patient has "currently active" second malignancy, other than non-melanoma skin cancer. Patients are not considered to have a "currently active" malignancy if they have completed therapy \>5 years previously and have no known evidence of residual or recurrent disease.
• Current symptomatic cord compression requiring surgery or radiation therapy
• Prior chemotherapy for prostate cancer
• Patient is using supplements or complementary medicines/botanicals. Patients should review the label with their doctor prior to enrolment. The following exceptions are permitted at screening and during the course of the study.
• Conventional multivitamin supplements
• Selenium
• Lycopene
• Soy supplements
• Vitamin E
• Fish oil supplements
• Vitamin D
• Glucosamine supplements
• Age-related eye disease vitamins
• Ginkgo biloba

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

UTHealth Memorial Hermann Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

sipuleucel-T; Docetaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Robert J Amato, DO

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director and Professor, Department of Internal Medicine, Division of Oncology

Study Record Dates

• First Submitted: May 19, 2016
• First Posted: June 8, 2016
• Study Start: December 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2021
• Last Updated: October 30, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)