Sipuleucel-T, CT-011, and Cyclophosphamide for Advanced Prostate Cancer

NCT01420965 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 11C0231
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Sipuleucel-T is a new treatment for advanced stage prostate cancer. It takes cells from a person with prostate cancer and treats them in the laboratory. Then it returns the cells to the person to help the immune system fight the cancer. Sipuleucel-T may be combined with the drug CT-011 to boost its ability to kill cancer cells. The chemotherapy drug cyclophosphamide will also be given, either before or after the cells are collected at the start of the treatment. Objectives: \- To test the effectiveness of Sipuleucel-T, CT-011, and cyclophosphamide for prostate cancer. Eligibility: \- Men at least 18 years of age who have advanced prostate cancer. Design:

• Participants will be screened with a medical history, physical exam, blood and urine tests, and imaging studies.
• This study has two parts, with different participants in each part. All participants will be monitored with frequent blood tests and imaging studies.
• Part I:
• Participants will provide cells for the Sipuleucel-T treatment three times. The first time will be 3 days before the chemotherapy. The second time will be 10 days after chemotherapy. The third time will be 24 days after chemotherapy.
• Participants will have one dose of cyclophosphamide the day before the first dose of Sipuleucel-T.
• Participants will have Sipuleucel-T about 3 days after each cell donation.
• Part II:
• Participants will be in three groups: Sipuleucel-T given alone, given with CT-011, or given with both cyclophosphamide and CT-011.
• Participants will provide cells for the Sipuleucel-T treatment three times, as in Part I.
• Participants will have Sipuleucel-T about 3 days after each cell donation, and will receive treatment with the other drugs as directed by the study doctors.

Conditions

Prostatic Neoplasms

Keywords

Anti PD-1 Monoclonal Antibody; Vaccine; Autologous Cellular Immunotherapy; Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Determine Feasibility of Provenge Plus Low-dose Cyclophosphamide as Well as the Immune Efficacy of Provenge Alone Versus Provenge Plus Low-dose Cyclophosphamide and Anti PD1 Monoclonal Antibodies (CT011) on the Change in Specific Immune Response.

  2 years

Secondary Outcomes (1)

• Determine Whether the Combination of Low Dose-Cyclophosphamide and Anti PD1 Monoclonal Antibodies (CT-011) With Provenge(tm) Lead to Improvement in Increase Progression Free Survival (PFS) and Overall Survival (OS) in Patients With Advanced, Min...

  2 years

Study Arms (3)

Arm A

ACTIVE COMPARATOR

Sipuleucel-T autologous active cellular immunotherapy only for 3 cycles (cycle = 14 days)

Other: Sipuleucel-T (Provenge)

Arm B

EXPERIMENTAL

Sipuleucel-T for 3 cycles (cycle = 14 days) + CT-011 (3mg/kg) IV infusion delivered over approximately 2 hours, 2 days after each Sipuleucel-T infusion

Drug: CT-011 (Anti-PD1 Antibody); Other: Sipuleucel-T (Provenge)

Arm C

EXPERIMENTAL

Sipuleucel-T for 3 cycles (cycle = 14 days)+ cyclophosphamide (125 or 250mg/m2) IV \[first cycle only\] + CT-011 (3mg/kg) IV infusion delivered over approximately 2 hours, 2 days after each Sipuleucel-T infusion

Drug: CT-011 (Anti-PD1 Antibody); Other: Sipuleucel-T (Provenge); Drug: Cyclophosphamide

Interventions

CT-011 (Anti-PD1 Antibody) DRUG

Immune Enhancer

Also known as: Anti-PD1 Antibody

Arm B; Arm C

Sipuleucel-T (Provenge) OTHER

Vaccine

Also known as: Provenge

Arm A; Arm B; Arm C

Cyclophosphamide DRUG

Low dose- Immune Enhancer

Also known as: Cytoxan

Arm C

Eligibility Criteria

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

You may qualify if:

• Patients must have histopathological documentation of prostate cancer prior to starting this study.
• Patients must have metastatic progressive castrate-resistant prostate cancer defined as progressive disease (see below) despite surgical castration or ongoing use of gonadotropin-releasing hormone agonists with confirmed castrate levels of testosterone. Criteria of progression for trial eligibility are defined from the Prostate Cancer Clinical Trials Working Group-253. Clinically progressive prostate cancer must be evidenced and documented by any of the following parameters:
• Two consecutively rising PSA values at a minimum of 1-week intervals (2.0 ng/mL is the minimum starting value for PSA)
• Appearance of one or more new lesions on bone scans
• Progressive measurable disease by RECIST 1.1
• Patients on flutamide for at least 6 months must have disease progression at least 4 weeks after withdrawal. Patients on bicalutamide or nilutamide for at least 6 months must have progression at least 6 weeks after withdrawal.2.1.1.4 Performance Status: ECOG 0-1 or Karnofsky 80-100% (asymptomatic or minimally symptomatic from metastatic disease).
• No previous chemotherapy use.
• No therapeutic immunosuppression or immunomodulation altering bone marrow function within 6 weeks prior to study entry e.g. G-CSF, GM-CSF, EPO, prednisone etc.
• Must have adequate:
• Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl. Platelets greater than or equal to 100,000/mcl.
• Renal function: Creatinine less than or equal to 1.5 times institutional upper limit normal (ULN)
• Hepatic function: Bilirubin less than or equal to 1.5 x ULN (CTCAE v4.0 grade 1) except patients with Gilbert's disease (up to 5.0 mg/dL). SGOT and alkaline phosphatase less than or equal to 2.5 x ULN.
• Normal Cardiac function: ECG with no evidence of arrhythmia, conduction abnormality or ischemia. No active coronary artery disease; no New York Heart Association class II, III or IV disease; no arrhythmia requiring treatment.
• Must willing and able to sign an informed consent document that explains the neoplastic nature of the disease, the procedures to be followed, the experimental nature of the treatment, alternative treatment and potential risks and toxicities.

You may not qualify if:

• Concurrent treatment with any other cancer therapies including radiation (except palliative radiation therapy for bone metastases), chemotherapy or other investigational agent(s). Androgen suppression therapy will be allowed.
• History of a second active malignancy in the last 2 years other than non-melanoma skin cancers.
• Patients being chronically treated with immunosuppressive drugs such as cyclosporin, adrenocorticotropic hormone (ACTH).
• Concurrent use of systemic glucocorticoids within 4 weeks prior to trial entry
• Patients who have acquired, hereditary, or congenital immunodeficiencies including cellular immunodeficiencies, hypogammaglobulinemia and dysgammaglobulinemia.
• CNS, lung, or liver metastasis, because of the poor prognosis, and potential inability to meet study endpoints.
• Serious active infection at the time of pre-study screening.
• Positive HIV or Hepatitis C antibodies or Hepatitis B anti-core antibodies, because immunotherapies rely on intact immune systems, and toxicities may be exacerbated by the presence of infection.

Sponsors & Collaborators

• Augusta University: lead

Study Sites (1)

Georgia Regents University

Augusta, Georgia, 30912, United States

Location

Related Publications (3)

• Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010 Aug;19(8):1893-907. doi: 10.1158/1055-9965.EPI-10-0437. Epub 2010 Jul 20.

  PMID: 20647400 BACKGROUND

• Gittes RF. Carcinoma of the prostate. N Engl J Med. 1991 Jan 24;324(4):236-45. doi: 10.1056/NEJM199101243240406. No abstract available.

  PMID: 1985245 BACKGROUND

• Crawford ED, Eisenberger MA, McLeod DG, Spaulding JT, Benson R, Dorr FA, Blumenstein BA, Davis MA, Goodman PJ. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med. 1989 Aug 17;321(7):419-24. doi: 10.1056/NEJM198908173210702.

  PMID: 2503724 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

pidilizumab; spartalizumab; sipuleucel-T; 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)

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

Results Point of Contact

• Title: Dr. Samir Khleif
• Organization: Georgetown University

snk48@georgetown.edu

(202) 687-0100

Study Officials

• Samir N. Khleif, MD

  Augusta University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cancer Center Director

Study Record Dates

• First Submitted: August 19, 2011
• First Posted: August 22, 2011
• Study Start: September 1, 2012
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: July 10, 2019
• Results First Posted: July 10, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)