Prostate Cancer Adenocarcinoma in SituPhase 1/2NCT01696877
A Neoadjuvant Study of Androgen Ablation Combined With Cyclophosphamide and GVAX Vaccine for Localized Prostate Cancer
A Phase 1/2 study testing degarelix acetate, Cyclophosphamide and GVAX in people with Prostate Cancer Adenocarcinoma in Situ, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
This research is being done to see if an investigational prostate cancer vaccine, called GVAX, can safely be given together with a single intravenous injection of a drug called cyclophosphamide to men that will undergo surgery to remove their cancerous prostate glands who have also received standard hormonal therapy. Read more about this study
- Who is it for?
- Ages 21 years and older, men only
- Conditions the study is for
- Prostate Cancer Adenocarcinoma in Situ
- What is being tested?
- degarelix acetate, Cyclophosphamide and GVAX
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jan 2013to 18 Dec 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed adenocarcinoma of the prostate (clinical stage T1c-T3b, N0, M0) without involvement of lymph nodes, bone, or visceral organs
- Initial prostate biopsy is available for central pathologic review, and is confirmed to show at least 2 positive cores and a maximum Gleason sum of ≥ 7
- Radical prostatectomy has been scheduled at Johns Hopkins Hospital
- Age ≥ 21 years
- Eastern Cooperative Oncology Group performance status 0-1, or Karnofsky score ≥ 70%
- Adequate bone marrow, hepatic, and renal function:
Show all 17Show fewer
- White Blood Count > 3,000 cells/mm3
- Absolute neutrophil count > 1,500 cells/mm3
- Hemoglobin > 9.0 g/dL
- Platelet count > 100,000 cells/mm3
- Serum creatinine < 2.0 mg/dL
- Serum bilirubin < 2 mg/dL
- Alanine aminotransferase < 2 × upper limit of normal (ULN)
- Aspartate aminotransferase < 2 × ULN
- Alkaline phosphatase < 2 × ULN
- Willingness to provide written informed consent and HIPAA authorization for the release of personal health information, and the ability to comply with the study requirements (note: HIPAA authorization will be included in the informed consent)
- Willingness to use barrier contraception from the time of cyclophosphamide and/or GVAX administration until the time of prostatectomy.
Who cannot join
- Presence of known lymph node involvement or distant metastases
- Other histologic types of prostate cancers such as ductal, sarcomatous, lymphoma, small cell, and neuroendocrine tumors
- Prior radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for prostate cancer
- Prior immunotherapy/vaccine therapy for prostate cancer
- Previous or concurrent use of cyclophosphamide
- Concomitant treatment with other hormonal therapy or 5a-reductase inhibitors
Show all 14Show fewer
- Current use of systemic corticosteroids or use of corticosteroids within 4 weeks of enrollment (inhaled corticosteroids for asthma or Chronic obstructive pulmonary disease are permitted)
- Use of experimental agents for prostate cancer within the past 3 months
- Known allergy to cyclophosphamide or G-colony stimulating factor /granulocytemacrophage-colony stimulating factor
- Known hypersensitivity to materials of bovine origin (e.g. fetal bovine serum), or other components of GVAX which include Dimethyl sulfoxide and hydroxyethyl starch as well as small amounts of porcine trypsin and DNase
- History or presence of autoimmune disease requiring systemic immunosuppression (including but not limited to: inflammatory bowel disease, systemic lupus erythematosus, vasculitis, rheumatoid arthritis, scleroderma, multiple sclerosis, hemolytic anemia, Sjögren syndrome, and sarcoidosis)
- Other concurrent malignancies, with the exception of non-melanoma skin cancers and superficial bladder cancer
- Uncontrolled major active infectious, cardiovascular, pulmonary, hematologic, or psychiatric illnesses that would make the patient a poor study candidate
- Known prior or current history of HIV and/or hepatitis B/C
Trial locations and contacts
1 site in 1 country.
United States1 site
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231
About this study
Official title: A Neoadjuvant Immunologic Study of Androgen Deprivation Therapy Combined With a Granulocytemacrophage-colony Stimulating Factor F-secreting Allogeneic Prostate Cancer Vaccine and Low-dose Cyclophosphamide in Men With High-risk Localized Prostate Cancer Undergoing Radical Prostatectomy
This research is being done to see if an investigational prostate cancer vaccine, called GVAX, can safely be given together with a single intravenous injection of a drug called cyclophosphamide to men that will undergo surgery to remove their cancerous prostate glands who have also received standard hormonal therapy.
Read the detailed description
Cancer immunotherapy refers broadly to approaches which attempt to treat cancer by activating immune responses directed against malignant tissue. Prostate GVAX is an allogeneic cell-based prostate cancer vaccine composed of two irradiated cell lines (PC3 and LNCaP) that have been genetically modified to secrete granulocyte-macrophage colony-stimulating factor (granulocytemacrophage-colony stimulating factor). The release of granulocytemacrophage-colony stimulating factor by these modified tumor cells serves to recruit dendritic cells which then present tumor antigens to T-cells, thus initiating antitumor immune responses.
However, abundant preclinical data show that, when used alone, cell-based immunotherapy is unable to break specific T-cell tolerance in tumor-bearing hosts. Studies in an autochthonous prostate cancer mouse model have shown that giving low-dose cyclophosphamide prior to a cell-based granulocytemacrophage-colony stimulating factor-secreting vaccine abrogates immune tolerance through augmentation of CD8+ T cell infiltration in the prostate, transient depletion of regulatory T cells (Tregs), and increased expression of dendritic cell maturation markers. Enhancement of antitumor immunity has also been observed in other preclinical models where cyclophosphamide was given in sequence with granulocytemacrophage-colony stimulating factor-secreting immunotherapy for the treatment of breast and pancreatic cancers. These preclinical data are supported by early-phase clinical trials combining GVAX with low-dose cyclophosphamide in pancreatic and breast cancers.
Furthermore, emerging evidence suggests that androgen deprivation therapy (ADT) itself has profound effects on the host immune system, resulting in thymic regeneration and enhancement of antitumor immunity. In addition, preclinical and clinical studies demonstrate that ADT augments prostate cancer-specific immune responses induced by immunotherapy, suggesting that ADT may act synergistically with immunotherapy. Based on data from mouse models as well as human clinical trials, it has been suggested that prostate cancer immunotherapy may be most effective when administered in the setting of an androgen-suppressed environment.
Building on these findings, investigators have designed a study to assess the use of ADT given alone or administered following immunization with low-dose cyclophosphamide and prostate GVAX, in patients undergoing radical prostatectomy. Investigators aim (1) to determine whether ADT is immunogenic in men with localized prostate cancer by evaluating T-cell infiltration in harvested prostate glands; (2) to determine whether administering ADT after low-dose cyclophosphamide and prostate GVAX augments immune infiltration into the prostate gland; and (3) to investigate whether this combinatorial immuno-hormonal approach is safe and feasible. Investigators hypothesize that the combination of ADT and cyclophosphamide/GVAX will produce significantly greater antitumor immune responses than would ADT used alone.
- Conditions
- Prostate Cancer Adenocarcinoma in Situ
- Being tested
- degarelix acetate, Cyclophosphamide, GVAX
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
degarelix acetateDrug
Also called Firmagon
Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow.
CyclophosphamideDrug
Also called Cytoxan, Neosar
Cyclophosphamide as a potent enhancer of immune responses to GVAX. cyclophosphamide is used as an immune suppressor in many autoimmune disorders.
GVAXDrug
Also called granulocytemacrophage -colony stimulating factor -secreting cell-based (PC3/LNCaP)immunotherapy
GVAX is granulocytemacrophage -colony stimulating factor -secreting allogeneic cell-based vaccine as immunotherapy for prostate cancer
| Study group | Role | What they receive |
|---|---|---|
| Degarelix | Active comparator | Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg at 14 (±3) days prior to surgery. A telephone follow-up interview (or an in-person clinic visit) to evaluate for adverse events will occur 28 (±21) days after prostatectomy. Patients will then be followed by their urologists according to standard institutional practices, but will require prostate-specific antigen evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3. Receives: Drug: degarelix acetate |
| Cyclophosphamide, GVAX and Degarelix | Experimental | Cyclophosphamide will be given at a dose of 200 mg/m2 as a single intravenous infusion. 1 day later, prostate GVAX will be administered as five 0.8-mL intradermal injections of PC3 (2.5 × 108 cells) and five 0.5-mL intradermal injections of LNCaP (2.5 × 108 cells), for a total dose of 5 × 108 cells. On day 14, Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg. Receives: Drug: degarelix acetate; Drug: Cyclophosphamide; Drug: GVAX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intraprostatic CD8+ T Cell Infiltration
CD8+ T cell infiltration (quantified as log[CD8 density]) into the prostate from harvested prostate glands in men with localized prostate cancer receiving neoadjuvant Androgen deprivation therapy alone (2 weeks prior to surgery), or cyclophosphamide and GVAX followed by Androgen deprivation therapy, (with cyclophosphamide/GVAX administered 4 weeks prior to prostatectomy, and Androgen deprivation therapy administered 2 weeks prior to prostatectomy).
Measured: 2 years
Secondary outcomes (7)
Intraprostatic CD4+ T Cell and Treg Infiltration
Number of participants with CD4+ T cell and Treg infiltration into the prostate.
Measured: 2 years
Quantification of Tissue Androgen Concentrations
Tissue androgen concentrations (testosterone, dihydrotestosterone), and androgen receptor (AR) protein expression in prostate specimens
Measured: 2 years
Quantification of Markers of Apoptosis
Amount of apoptosis (activated caspase 3) and proliferation (Ki-67) in prostate tumor specimens
Measured: 2 years
Pathological Complete Responses
Number of participants with pathological complete response (pCR)
Measured: 2 years
Serum Antibodies to Prostate-associated Antigens
Number of participants with generation of novel antibodies to prostate-associated antigens in the serum of patients, after the initiation of protocol therapy
Measured: 2 years
Prostate-specific Antigen Response Rate
Number of participants with Prostate-specific antigen response
Measured: 2 years
Percentage of Participants Without Prostate Specific Antigen Recurrence at 24 Months After Surgery
Percentage of participants in each arm who were free of prostate specific antigen recurrence (i.e. prostate specific antigen remained undetectable after prostatectomy) at 24 months after undergoing surgery.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2012 (estimated)
- Study start18 Jan 2013
- Primary completionAug 2017
- Study completion18 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostate Cancer Adenocarcinoma in SituStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- David H. Koch Charitable Foundation, BioSante Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Emmanual Antonarakis, M.D, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01696877
- Sponsor's protocol ID
- J1265
- Other IDs
- NA_00073453
- Status last verified
- Mar 2019
- First submitted
- 14 Sep 2012
- Last updated
- 28 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Neoadjuvant Immunologic Study of Androgen Deprivation Therapy Combined With a Granulocytemacrophage-colony Stimulating Factor F-secreting Allogeneic Prostate Cancer Vaccine and Low-dose Cyclophosphamide in Men With High-risk Localized Prostate Cancer Undergoing Radical Prostatectomy
- ClinicalTrials.gov ID
- NCT01696877
- Acronym / sponsor ID
- J1265
- Conditions
- Prostate Cancer Adenocarcinoma in Situ
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- David H. Koch Charitable Foundation, BioSante Pharmaceuticals
- Study start
- 18 Jan 2013 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- 18 Dec 2018 (actual)
- First posted
- 1 Oct 2012 (estimated)
- Results
- Posted 1 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research is being done to see if an investigational prostate cancer vaccine, called GVAX, can safely be given together with a single intravenous injection of a drug called cyclophosphamide to men that will undergo surgery to remove their cancerous prostate glands who have also received standard hormonal therapy.
Detailed description
Cancer immunotherapy refers broadly to approaches which attempt to treat cancer by activating immune responses directed against malignant tissue. Prostate GVAX is an allogeneic cell-based prostate cancer vaccine composed of two irradiated cell lines (PC3 and LNCaP) that have been genetically modified to secrete granulocyte-macrophage colony-stimulating factor (granulocytemacrophage-colony stimulating factor). The release of granulocytemacrophage-colony stimulating factor by these modified tumor cells serves to recruit dendritic cells which then present tumor antigens to T-cells, thus initiating antitumor immune responses.
However, abundant preclinical data show that, when used alone, cell-based immunotherapy is unable to break specific T-cell tolerance in tumor-bearing hosts. Studies in an autochthonous prostate cancer mouse model have shown that giving low-dose cyclophosphamide prior to a cell-based granulocytemacrophage-colony stimulating factor-secreting vaccine abrogates immune tolerance through augmentation of CD8+ T cell infiltration in the prostate, transient depletion of regulatory T cells (Tregs), and increased expression of dendritic cell maturation markers. Enhancement of antitumor immunity has also been observed in other preclinical models where cyclophosphamide was given in sequence with granulocytemacrophage-colony stimulating factor-secreting immunotherapy for the treatment of breast and pancreatic cancers. These preclinical data are supported by early-phase clinical trials combining GVAX with low-dose cyclophosphamide in pancreatic and breast cancers.
Furthermore, emerging evidence suggests that androgen deprivation therapy (ADT) itself has profound effects on the host immune system, resulting in thymic regeneration and enhancement of antitumor immunity. In addition, preclinical and clinical studies demonstrate that ADT augments prostate cancer-specific immune responses induced by immunotherapy, suggesting that ADT may act synergistically with immunotherapy. Based on data from mouse models as well as human clinical trials, it has been suggested that prostate cancer immunotherapy may be most effective when administered in the setting of an androgen-suppressed environment.
Building on these findings, investigators have designed a study to assess the use of ADT given alone or administered following immunization with low-dose cyclophosphamide and prostate GVAX, in patients undergoing radical prostatectomy. Investigators aim (1) to determine whether ADT is immunogenic in men with localized prostate cancer by evaluating T-cell infiltration in harvested prostate glands; (2) to determine whether administering ADT after low-dose cyclophosphamide and prostate GVAX augments immune infiltration into the prostate gland; and (3) to investigate whether this combinatorial immuno-hormonal approach is safe and feasible. Investigators hypothesize that the combination of ADT and cyclophosphamide/GVAX will produce significantly greater antitumor immune responses than would ADT used alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Degarelix | Active comparator | Drug: degarelix acetateDegarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg at 14 (±3) days prior to surgery. A telephone follow-up interview (or an in-person clinic visit) to evaluate for adverse events will occur 28 (±21) days after prostatectomy. Patients will then be followed by their urologists according to standard institutional practices, but will require prostate-specific antigen evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3. |
| Cyclophosphamide, GVAX and Degarelix | Experimental | Drug: degarelix acetate, Drug: Cyclophosphamide, Drug: GVAXCyclophosphamide will be given at a dose of 200 mg/m2 as a single intravenous infusion. 1 day later, prostate GVAX will be administered as five 0.8-mL intradermal injections of PC3 (2.5 × 108 cells) and five 0.5-mL intradermal injections of LNCaP (2.5 × 108 cells), for a total dose of 5 × 108 cells. On day 14, Degarelix will be administered as three 80 mg subcutaneous injections, for a total dose of 240 mg. |
Who may qualify
- Ages
- 21 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically confirmed adenocarcinoma of the prostate (clinical stage T1c-T3b, N0, M0) without involvement of lymph nodes, bone, or visceral organs
- Initial prostate biopsy is available for central pathologic review, and is confirmed to show at least 2 positive cores and a maximum Gleason sum of ≥ 7
- Radical prostatectomy has been scheduled at Johns Hopkins Hospital
- Age ≥ 21 years
- Eastern Cooperative Oncology Group performance status 0-1, or Karnofsky score ≥ 70%
Key exclusion criteria (14 listed)
- Presence of known lymph node involvement or distant metastases
- Other histologic types of prostate cancers such as ductal, sarcomatous, lymphoma, small cell, and neuroendocrine tumors
- Prior radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for prostate cancer
- Prior immunotherapy/vaccine therapy for prostate cancer
- Previous or concurrent use of cyclophosphamide
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| degarelix acetateAlso: FirmagonDegarelix Acetate is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It works by decreasing the amount of testosterone in the body,which the tumor needs to grow. | Drug | Cyclophosphamide, GVAX and Degarelix, Degarelix |
| CyclophosphamideAlso: Cytoxan, NeosarCyclophosphamide as a potent enhancer of immune responses to GVAX. cyclophosphamide is used as an immune suppressor in many autoimmune disorders. | Drug | Cyclophosphamide, GVAX and Degarelix |
| GVAXAlso: granulocytemacrophage -colony stimulating factor -secreting cell-based (PC3/LNCaP)immunotherapyGVAX is granulocytemacrophage -colony stimulating factor -secreting allogeneic cell-based vaccine as immunotherapy for prostate cancer | Drug | Cyclophosphamide, GVAX and Degarelix |
Primary outcome
Intraprostatic CD8+ T Cell Infiltration
Time frame: 2 years
CD8+ T cell infiltration (quantified as log[CD8 density]) into the prostate from harvested prostate glands in men with localized prostate cancer receiving neoadjuvant Androgen deprivation therapy alone (2 weeks prior to surgery), or cyclophosphamide and GVAX followed by Androgen deprivation therapy, (with cyclophosphamide/GVAX administered 4 weeks prior to prostatectomy, and Androgen deprivation therapy administered 2 weeks prior to prostatectomy).
7 secondary outcomes
Intraprostatic CD4+ T Cell and Treg Infiltration
Time frame: 2 years
Quantification of Tissue Androgen Concentrations
Time frame: 2 years
Quantification of Markers of Apoptosis
Time frame: 2 years
Pathological Complete Responses
Time frame: 2 years
Serum Antibodies to Prostate-associated Antigens
Time frame: 2 years
Prostate-specific Antigen Response Rate
Time frame: 2 years
Percentage of Participants Without Prostate Specific Antigen Recurrence at 24 Months After Surgery
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emmanual Antonarakis, M.D principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing degarelix acetate, Cyclophosphamide and GVAX in people with Prostate Cancer Adenocarcinoma in Situ, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intraprostatic CD8+ T Cell Infiltration (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2019.