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Docetaxel and PROSTVAC for Metastatic Castration-Sensitive Prostate Cancer

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ClinicalTrials.gov Identifier: NCT02649855
Recruitment Status : Recruiting
First Posted : January 8, 2016
Last Update Posted : September 12, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

Metastatic castrate-sensitive prostate cancer is cancer that has spread beyond the prostate area. It can be controlled by lowering the amount of testosterone in the body. This is called androgen deprivation therapy (ADT). The vaccine PROSTVAC might help the immune system kill cancer cells. Researchers want to add PROSTVAC and docetaxel chemotherapy to ADT. They think this may work better against prostate cancer than ADT alone.

Objective:

To test if adding PROSTVAC and docetaxel to ADT works better against prostate cancer than ADT alone.

Eligibility:

Men ages 18 years and over with metastatic castrate-sensitive prostate cancer

Design:

Participants will be screened with:

Physical exam

Medical history

Blood tests

Possible CT, MRI, or bone scan: Participants lie in a machine. The machine takes pictures of the body.

Electrocardiogram: Soft electrodes are stuck to the skin to record heart signals.

Participants will have 2 optional tumor biopsies during the study.

Participants will join 1 of 2 groups. Both groups will get:

ADT

Docetaxel by vein

Steroids by mouth or vein before each docetaxel infusion

PROSTVAC injection

Both groups first have ADT. One to 4 months after, they have:

Group A:

Docetaxel every 3 weeks for 6 cycles

PROSTVAC 3 weeks after the last infusion

Booster injections 2 weeks later and then every 3 weeks, for 6 boosters total

Group B:

PROSTVAC

Booster 2 weeks later

Docetaxel hours later

Docetaxel and the booster every 3 weeks for 6 cycles

Participants will have a visit 4-5 weeks after the last treatment. They will then have visits every 12 weeks.

Participants will be followed for up to 15 years. This includes physical exams every year for 5 years.


Condition or disease Intervention/treatment Phase
Prostate Cancer Prostate Neoplasms Neoplasms, Prostatic Biological: PROSTVAC-V Biological: PROSTVAC-F Drug: Docetaxel Phase 2

Detailed Description:

Background:

  • A phase III trial demonstrated that combining docetaxel and androgen deprivation therapy (ADT) significantly improved survival (57.6 vs 44.0 months (HR=0.56, (0.44-0.70), p <0.0001) for men with metastatic castration sensitive prostate cancer (mCSPC).
  • PROSTVAC (developed by the National Cancer Institute [NCI] and licensed to Bavarian Nordic Immunotherapeutics, Mountain View, CA) is a therapeutic cancer vaccine for prostate cancer.
  • Preclinical and clinical studies support the potential synergy in the combination of docetaxel and PROSTVAC. The potential to combine docetaxel with vaccine in mCSPC could improve upon the survival advantage that has been previously seen.

Objectives:

Primary

-To determine if PROSTVAC combined with docetaxel is able to induce greater antigen spreading (i.e. a broader immune response) with greater associated response score compared to docetaxel alone after 19 weeks.

Key Eligibility Criteria:

  • Must have castrate sensitive prostate cancer (rising PSA and testosterone over 100) or is within 134 days of starting ADT (Arm A or B) or within 28 days of start ADT (Arm C)
  • Histopathological confirmation of prostate cancer
  • Patients must have metastatic disease
  • Patients must have a performance status of 0 to 2 according to the ECOG criteria
  • Patients must have adequate bone marrow, hepatic, and renal function

Design

  • This is a randomized trial of ADT followed by simultaneous docetaxel 75 mg/m(2) q3 weeks x 6 cycles + PROSTVAC q3 weeks x 6 cycles versus ADT followed by sequential docetaxel 75 mg/m(2) q3 weeks x 6 cycles followed by PROSTVAC q3 weeks x 6 cycles in men with newly diagnosed mCSPC.
  • Patients who have not started ADT or who have been on ADT 28 days or fewer will be assigned to treatment with PROSTVAC for 4 - 6 injections followed by docetaxel 75 mg/m2 q3 weeks x 6 cycles.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Docetaxel and Prostvac for Metastatic Castration Sensitive Prostate Cancer
Study Start Date : January 7, 2016
Estimated Primary Completion Date : January 1, 2019
Estimated Study Completion Date : January 1, 2020

Resource links provided by the National Library of Medicine

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

Arm Intervention/treatment
Experimental: A/Sequential docetaxel followed by PROSTVAC
Standard ADT followed by simultaneous docetaxel + prostvac
Biological: PROSTVAC-V
It is a recombinant vaccinia virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules (B7.1, ICAM-1, and LFA-3). It will be given subcutaneously, 2x10(8) infectious units.

Biological: PROSTVAC-F
It is a recombinant fowlpox virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules (B7.1, ICAM-1, and LFA-3). It will be given subcutaneously, 1x10(9) infectious units.

Drug: Docetaxel
It is commercially available. It will be administered at 75 mg/m(2) intravenously.

Experimental: B/ Combined docetaxel with PROSTVAC
Standard ADT followed by sequential docetaxel + prostvac
Biological: PROSTVAC-V
It is a recombinant vaccinia virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules (B7.1, ICAM-1, and LFA-3). It will be given subcutaneously, 2x10(8) infectious units.

Biological: PROSTVAC-F
It is a recombinant fowlpox virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules (B7.1, ICAM-1, and LFA-3). It will be given subcutaneously, 1x10(9) infectious units.

Drug: Docetaxel
It is commercially available. It will be administered at 75 mg/m(2) intravenously.

Experimental: C/ PROSTVAC prior to docetaxel
Standard ADT followed by prostvac, then docetaxel
Biological: PROSTVAC-V
It is a recombinant vaccinia virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules (B7.1, ICAM-1, and LFA-3). It will be given subcutaneously, 2x10(8) infectious units.

Biological: PROSTVAC-F
It is a recombinant fowlpox virus vector vaccine containing the genes for human PSA and three co-stimulatory molecules (B7.1, ICAM-1, and LFA-3). It will be given subcutaneously, 1x10(9) infectious units.

Drug: Docetaxel
It is commercially available. It will be administered at 75 mg/m(2) intravenously.




Primary Outcome Measures :
  1. Determine if PROSTVAC combined with docetaxel is able to induce greater antigen spreading (i.e. a broader immune response) with greater associated response score compared to docetaxel alone after 19 weeks. [ Time Frame: 2 years ]
    Response/efficacy.


Secondary Outcome Measures :
  1. Scores from the subset consisting of previously untreated patients on the superior randomized arm will be tested against the patients on the new PROSTVAC then docetaxel cohort (Arm C). [ Time Frame: 2 years ]
    Response/efficacy.

  2. Patients getting PROSTVAC prior to chemotherapy will be evaluated for antigen specific responses after completing vaccine followed by 6cycles of chemotherapy. [ Time Frame: 2 years ]
    Antigen response to treatment.

  3. Antigen specific responses for patients getting PROSTVAC prior tochemotherapy. [ Time Frame: after completing vaccine followed by 6 cycles of chemotherapy ]
    Antigen response to treatment.

  4. Evaluate immunologic response among immune subsets (flow cytometry). [ Time Frame: 2 years ]
    Immune response.

  5. Evaluate antigen-specific immune responses and response scores at39 weeks in both groups and 1 year in both groups. [ Time Frame: 1 year ]
    Immune response.

  6. Compare antigen-specific immune responses and response scores at19 weeks in the combination arm (docetaxel and PROSTVAC) andcompared to 39 weeks in the sequence arm (docetaxel followedby PROSTVAC) . [ Time Frame: 1 year ]
    Immune response.

  7. Evaluate radiographic and biochemical time to progression in both groups. [ Time Frame: 2 years ]
    Response/efficacy.

  8. Evaluate proportion of patients with PSA >0.2 ng/ml at 6 and 12 months. [ Time Frame: at 6 and 12 months ]
    Response/efficacy.

  9. Evaluate changes in the tumor microenvironment with biopsies preand post (2 cycles of vaccine therapy; alone or combination)when feasible. [ Time Frame: pre and post 2 cycles of vaccine therapy ]
    Response/efficacy.

  10. Evaluate Pharmacogenomic studies to evaluate drug metabolism andtransporters. [ Time Frame: 2 years ]
    Pharmacogenomic effects.

  11. Evaluate overall survival. [ Time Frame: 2 years ]
    Response/efficacy.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Documented histopathological confirmation of prostate cancer-from a CLIA certified laboratory.
  • Patients must have metastatic disease, defined as at least one lesion on bone scan or at least one lesion that are measurable per RECIST 1.1. (Patients who have metastatic disease by these criteria prior to ADT, but then have changes after ADT that diminish the size of these lesions or changes on bone scan are still eligible.)
  • Patients must have a performance status of 0 to 2 according to the ECOG criteria
  • Patients must have adequate bone marrow, hepatic, and renal function with:

    • ANC greater than or equal to 1500/microL, without CSF support
    • Platelets greater than or equal to 100,000/microL
    • AST(SGOT) less than or equal to 2.5 times upper limit of normal (ULN);
    • ALT(SGPT) less than or equal to 2.5 times upper limit of normal (ULN);
    • Total serum bilirubin less than or equal to 1.5 times upper limit of normal (ULN), OR in patients with Gilbert s syndrome, a total bilirubin less than or equal to 3.0)
    • Serum albumin greater than or equal to 2.8 g/dL
    • Lipase < 2.0 times the upper limit of normal and no radiologic or clinical evidence of pancreatitis
    • Creatinine less than or equal to 1.5 times institutional upper limits of normal

OR

Creatinine clearance of greater than or equal to 50 ml/min/1.73 m(2) for patients with creatinine levels above institutional normal by 24-hour urine.

  • Willing to travel to the NIH for follow-up visits
  • 18 years of age or older.
  • Able to understand and sign informed consent.
  • May have had up to 24 months of ADT (testosterone suppression therapy in the nonmetastatic setting) and are at least 12 months removed from treatment
  • Men treated or enrolled on this protocol must also agree to use adequate contraception, prior to the study, for the duration of study participation, and 4 months after completion. Sexually active subjects and their female partners must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must also agree to use both a barrier method and a second method of birth control during the course on the study and for 4 months after the last dose of study drug(s). Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.
  • Must have started ADT for metastatic disease within 134 days (for Arm A and B) or within 28 days (for Arm C).

EXCLUSION CRITERIA:

  • Immunocompromised status due to:

    • Human immunodeficiency virus (HIV) positivity.
    • Active autoimmune diseases such as Addison s disease, Hashimoto s thyroiditis, systemic lupus erythematosus, Sj(SqrRoot)(Delta)gren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave s disease. Patients with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including CNS, heart, lungs, kidneys, skin, and GI tract will be allowed.
    • Other immunodeficiency diseases
  • Chronic administration (defined as daily or every other day for continued use > 14 days) of corticosteroids deemed systemic by investigator within 28 days before the first planned dose of PROSTVAC. Use of inhaled steroids, nasal sprays, and topical creams for small body areas is allowed.
  • Evidence of rising PSA on ADT
  • Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with patient s ability to carry out the treatment program.
  • Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to poxviral vaccines (e.g., vaccinia vaccine)
  • Known allergy to eggs, egg products, aminoglycoside antibiotics (for example, gentamicin or tobramycin).
  • History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that disrupts the epidermis
  • Previous serious adverse reactions to smallpox vaccination
  • Unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the Day 1 vaccination: (a) children less than or equal to 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with HIV.
  • Receipt of an investigational agent within 28 days (or 60 days for an antibody-based therapy) before the first planned dose of study drugs.
  • Patients who test positive for HBV or HCV
  • Uncontrolled hypertension (SBP>170/ DBP>105)
  • Patients who have had prior chemotherapy for prostate cancer.
  • The subject has had evidence within 2 years of the start of study treatment of another malignancy which required systemic treatment (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder).
  • The subject has active brain metastases or epidural disease.
  • Patients with greater than or equal to grade 2 peripheral neuropathy at baseline.
  • Patients with history of splenectomy

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): NCT02649855


Contacts
Contact: Anna C Couvillon, C.R.N.P. (301) 443-6211 couvilla@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike 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: Ravi A Madan, M.D. National Cancer Institute (NCI)

Additional Information:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02649855     History of Changes
Other Study ID Numbers: 160048
16-C-0048
First Posted: January 8, 2016    Key Record Dates
Last Update Posted: September 12, 2018
Last Verified: September 6, 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
PSA
Vaccine
Immunotherapy
Immune Response
Androgen Deprivation Therapy

Additional relevant MeSH terms:
Prostatic Neoplasms
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Vaccines
Docetaxel
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action