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PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer

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ClinicalTrials.gov Identifier: NCT02933255
Recruitment Status : Recruiting
First Posted : October 14, 2016
Last Update Posted : July 6, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

The immune system is the cells and organs in the body that recognize and fight infection and cancer. The PROSTVAC vaccine might teach the immune system to find and kill certain prostate cancer cells. Nivolumab is a drug that allows the immune system to fight tumors. Itmight help PROSTVAC work better.

Objective:

To test the safety and effectiveness of the combination of PROSTVAC and nivolumab. To test this for people with castration resistant prostate cancer and then for other people with localized prostate cancer who are candidates for surgical removal of the prostate.

Eligibility:

Men ages 18 and older with prostate cancer

Design:

Participants will be screened with:

Medical history

Physical exam

Blood and urine tests

Electrocardiogram

Bone scan

CT scan or MRI

Tumor sample. This may be from a previous procedure.

All participants will get a combination of the study drugs over 8 weeks. They will have 1 visit for the initial injection then 3 booster injection / nivolumab infusion visits. Blood will be tested at these visits.

Over the next 4 weeks, some participants will have:

An exam of the large intestine through the rectum.

CT and bone scans

Standard hormonal treatment

Option to continue treatment every 3 weeks if their disease does not get worse. They will be

have scans every 12 weeks.

Other participants will have surgery to remove the prostate in week 9.

Participants will have a safety visit about a month after their last treatment. This will include a physical exam, blood tests, and possibly scans.

If their cancer progresses, participants will leave the study and may enroll in a long-term follow-up study. They will be contacted once a year to ask about their cancer and treatment.


Condition or disease Intervention/treatment Phase
Prostate Cancer Biological: PROSTVAC-V/F Drug: Nivolumab Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 29 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer
Study Start Date : October 13, 2016
Estimated Primary Completion Date : August 1, 2020
Estimated Study Completion Date : August 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Lead-in mCRPC Cohort
PROSTVAC-V on week 0 followed by booster injection called PROSTVAC-F on 2, 4, 6 and 8 weeks. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Patients will undergo sigmoidoscopies on week 9 and restaging scans on week 11. If no PD, option to continue treatment every 3 weeks until intolerance or progression (evaluated radiographically every 12 weeks).
Biological: PROSTVAC-V/F
PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10^8 infectious units; PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10^9 infectious units.

Drug: Nivolumab
Nivolumab is to be administered as a flat dose of 240 mg over approximately 60-minutes via IV infusion.

Experimental: Neoadjuvant Cohort
PROSTVAC-V on week 0 followed by booster injection called PROSTVAC-F on 2, 4 and 8 weeks. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Patients will undergo prostatectomy on week 9.
Biological: PROSTVAC-V/F
PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10^8 infectious units; PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10^9 infectious units.

Drug: Nivolumab
Nivolumab is to be administered as a flat dose of 240 mg over approximately 60-minutes via IV infusion.




Primary Outcome Measures :
  1. Safety - lead-in mCRPC cohort [ Time Frame: After 10 patients ]
  2. Evaluate changes in T-cell infiltration in the tumor after neoadjuvant treatment [ Time Frame: From baseline to 10 weeks ]

Secondary Outcome Measures :
  1. Determine the change in peripheral PSA-specific T cells in patients treated with PROSTVAC and nivolumab [ Time Frame: 3-5 years ]
  2. Document any intraprostatic Treg cell infiltration with CD4+FOX-P3staining [ Time Frame: 3-5 years ]
  3. Document any PSA changes secondary to vaccination, including rate of biochemical recurrence after prostatectomy [ Time Frame: 3-5 Years ]
  4. Document any MRI changes secondary to treatment [ Time Frame: 3-5 years ]
  5. Evaluate changes in PDL-1 expression [ Time Frame: 3-5 years ]
  6. Document pathologic responses (including pathologic CR) [ Time Frame: 3-5 years ]
  7. Evaluate changes in immune cell subsets in the periphery [ Time Frame: 3-5 years ]
  8. Evaluate changes in soluble immune mediating factors (such as cytokines, etc.) in sera [ Time Frame: 3-5 years ]
  9. Evaluate changes in circulating tumor cells levels (for mCRPCcohort only) [ Time Frame: 3-5 years ]
  10. Safety (for localized prostate cancer cohorts) [ Time Frame: 3-5 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

For all cohorts except the CRPC lead in cohort, patients must have histopathological documentation of adenocarcinoma of the prostate prior to starting this study and evaluable biopsy tissue (e.g., unstained slides or blocks) available for analysis. If evaluable tissue is not available, the patient must agree to undergo a pre-vaccination prostate biopsy on study. For the CRPC lead in cohort, if histopathological documentation is unavailable, a rising PSA and a clinical course consistent with prostate cancer would be acceptable.

  • Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of PROSTVAC in combination with nivolumab, ipilimumab or both in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
  • ECOG performance status of 0 or 1.
  • Patients must not have other active invasive malignancies within the past 2 years (with the exception of non-melanoma skin cancers) (for CRPC cohort only).
  • Patients must be willing to travel to the study site for follow-up visits
  • All patients who have received prior vaccination with vaccinia virus (for smallpox immunization) must not have a history of adverse reaction to the vaccine.
  • The effects of PROSTVAC in combination nivolumab, ipilimumab or both on the developing human fetus are unknown. For this reason men must agree to use adequate contraception (abstinence, vasectomy) or female partner must use (intrauterine device (IUD), hormonal [birth control, pills, injections, or implants], tubal ligation] prior to study entry and for up to 5 months after the last dose.
  • Patients must understand and sign informed consent that explains the neoplastic nature of their disease, the procedures to be followed, the experimental nature of the treatment, alternative treatments, potential risks and toxicities, and the voluntary nature of participation.
  • Patients must have normal organ and marrow function as defined below:

    • hemoglobin greater than or equal to 8 g/dL
    • granulocytes greater than or equal to 1,500/mcL
    • platelets greater than or equal to 100,000/mcL
    • total bilirubin < 1.5 mg/dL (or less than or equal to 3.0 mg/dL in patients with Gilbert syndrome)
    • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal
    • creatinine less than or equal to 1.5 X ULN
  • For the lead in cohort:

    • Castrate testosterone level (<50ng/dl or 1.7nmol /L)
    • Progressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone:

      • Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer OR
      • PSA progression defined by sequence of rising values separated by >1 week (2 separate increasing values over a minimum of 2ng/ml (PCWG2 PSA eligibility criteria). If patients had been on flutamide, PSA progression is documented 4 weeks or more after withdrawal. For patients on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal.
    • Patients must agree to continue to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone agonist/antagonist or bilateral orchiectomy
  • For all other cohorts:

    • Patients must be a surgical candidate for radical prostatectomy based on standard workup of PSA, biopsy results, and if necessary supplemental imaging.
    • Patients must have chosen radical prostatectomy as their definitive treatment of choice for management of their prostate cancer.
    • No systemic steroid or steroid eye drop use within 2 weeks prior to initiation of experimental therapy. Limited doses of systemic steroids to prevent IV contrast, allergic reaction or anaphylaxis (in patients who have known contrast allergies) are allowed.

EXCLUSION CRITERIA:

  • Prior splenectomy.
  • The recombinant vaccinia vaccine should not be administered if the following apply to either recipients or, for at least 3 weeks after vaccination, their close household contacts (Close household contacts are those who share housing or have close physical contact):

    • persons with active or a history of eczema or other eczematoid skin disorders
    • those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne or other open rashes or wounds) until condition resolves
    • pregnant or nursing women; children under 3 years of age
  • Patients should have no evidence, as listed below, of being immunocompromised:

    • HIV positivity due to the potential for decreased tolerance and risk for severe side effects.
    • Hepatitis B or C positivity.
  • Concurrent use of systemic steroids or steroid eye drops. This is to avoid immunosuppression which may lead to potential complications with vaccinia (priming vaccination). Nasal, topical or inhaled steroid use is permitted.
  • Patients with known allergy to eggs or to compounds with a similar chemical or biologic composition to PROSTVAC, ipilimumab or nivolumab.
  • No prior immune checkpoint inhibitors (e.g., anti-CTLA4, anti-PD-1 or anti-PDL1) are allowed.
  • Other serious intercurrent illness.
  • Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment) or New York Heart Association class II IV congestive heart failure.
  • Patients with significant autoimmune disease that is active or potentially life threatening if activated.
  • Patients with clinically significant cardiomyopathy requiring treatment.
  • Patients with ongoing toxicities related to prior therapies targeting T cell coregulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody are excluded
  • No transfusion of blood or blood products within 2 weeks and no G-CSF or GM-CSF within 2 weeks prior to initiations of experimental therapy.
  • Contraindication to biopsy or prostatectomy (for sequential neoadjuvant cohorts only):

    • Bleeding disorders
    • Artificial heart valve
    • PT/PTT greater than or equal to 1.5 in patients not taking anticoagulation. Patients on anticoagulation (e.g. enoxaparin, oral anticoagulants) are eligible regardless of PT/PTT. Prior to biopsy, anticoagulation will be held per standard practice.
  • For patients with localized prostate cancer contraindication to MRI:

    • Patients weighing >136 kilograms (weight limit for the scanner tables)
    • Allergy to MR contrast agent
    • Patients with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable electronic devices
  • History of radiation proctitis (for lead-in CRPC cohort only)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02933255


Contacts
Contact: Myrna Rauckhorst, R.N. (240) 760-6069 mrauckhorst@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: James L Gulley, M.D. National Cancer Institute (NCI)

Additional Information:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02933255     History of Changes
Other Study ID Numbers: 170007
17-C-0007
First Posted: October 14, 2016    Key Record Dates
Last Update Posted: July 6, 2018
Last Verified: September 27, 2017

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Safety
Neoadjuvant
Prostatectomy
Immunotherapy
Vaccine

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs