Castration Levels of TestosteronePhase 2NCT03406858
Pembro and HER2Bi-Armed Activated T Cells in Treating Patients With Metastatic Castration Resistant Prostate Cancer
A Phase 2 study testing HER2Bi-Armed Activated T Cells, Laboratory Biomarker Analysis and Pembrolizumab in people with Castration Levels of Testosterone and Castration-Resistant Prostate Carcinoma, run by Barbara Ann Karmanos Cancer Institute at 1 site in United States.
Trial summary
This phase II trial studies how well pembrolizumab and HER2Bi-armed activated T cells work in treating patients with castration resistant prostate cancer that has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma, Prostate Carcinoma Metastatic in the Bone
- What is being tested?
- HER2Bi-Armed Activated T Cells, Laboratory Biomarker Analysis and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Jun 2018to 7 Nov 2022
- Phase
- Phase 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be willing and able to provide written informed consent/assent for the trial
- Have histologically confirmed prostate adenocarcinoma, with metastases
- Progression by either PSA, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for measurable disease or new areas of metastases on bone scan or symptom progression related to prostate cancer despite castrate levels of testosterone; (level < 50 ng/ml)
- Be agreeable to continue to maintain castrate levels of testosterone
- At least 2 weeks should have elapsed since any immunosuppressive therapy
- At least 4 weeks since prior chemotherapy for metastatic disease or at least 2 weeks since prior androgen targeting agents such as ketoconazole, abiraterone, enzalutamide, etc.
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- Discontinue anti-androgens prior to therapy; at least 6 weeks since last dose of bicalutamide or nilutamide and at least 4 weeks from last dose of flutamide
- Have normal bone marrow, renal and hepatic function as deemed by the treating physician and approved by the clinical principal investigator (PI) Dr. Vaishampayan
- Not have concurrent anti-cancer therapy
- Not have concurrent immunosuppressive therapy or medical condition likely to cause immunosuppression
- Have life expectancy > 6 months
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)/Zubrod performance scale
- Agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
- Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
- Within 10 days of treatment registration: Absolute neutrophil count (ANC) >= 1,500 /mcL
- Within 10 days of treatment registration: Platelets >= 100,000 / mcL
- Within 10 days of treatment registration: Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
- Within 10 days of treatment registration: Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
- Within 10 days of treatment registration: Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
- Within 10 days of treatment registration: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT] =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases
- Within 10 days of treatment registration: Albumin >= 2.5 mg/dL
- Within 10 days of treatment registration: International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
- Within 10 days of treatment registration: Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (> 10 mg of prednisone daily or equivalent steroid doses) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Has a known history of active TB (Bacillus tuberculosis)
- Has hypersensitivity to pembrolizumab or any of its excipients
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or has not recovered (i.e. =< grade 1 or at baseline) from adverse events due to agents administered earlier; Note: Subjects with =<grade 2 neuropathy are an exception to this criterion and may qualify for the study
- Has received major surgery, subject must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
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- Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Has known history of, or any evidence of active, non-infectious pneumonitis
- Has an active infection requiring systemic therapy
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject?s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Has known active hepatitis B (e.g. hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g. hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
- Has received a live vaccine within 30 days of planned start of study therapy; Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated vaccines, and are not allowed
- Has history of cardiac or pulmonary impairment either by clinical history or symptoms or cardiac ejection fraction < 40%
Trial locations and contacts
1 site in 1 country.
United States1 site
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
About this study
Official title: Phase II Trial of Immune Checkpoint Inhibitor With Anti-CD3 x Anti-HER2 Bispecific Antibody Armed Activated T Cells in Metastatic Castrate Resistant Prostate Cancer
This phase II trial studies how well pembrolizumab and HER2Bi-armed activated T cells work in treating patients with castration resistant prostate cancer that has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. HER2Bi-armed activated T cells are made using T cells and may target and kill cancer cells. Giving pembrolizumab and HER2Bi-armed activated T cells may work better in treating patients with castration resistant prostate cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the clinical efficacy of 8 infusions of HER2 HER2Bi-armed activated T cells (BATs) (up to 10^10/infusion) twice per week for 4 weeks in combination with pembrolizumab once every 3 weeks starting with one dose 3 weeks before the 1st BATs infusion, by assessing the percentage of patients free of clinical progression at 6 months after registration.
SECONDARY OBJECTIVES:
- Evaluate phenotype, cytokine profiles and IFN-gamma enzyme-linked immunosorbent spots (ELISpots), cytotoxicity and antibodies directed at laboratory prostate cancer cell lines for proof of principle of immune system activation and to correlate with clinical outcomes of response, progression free survival (PFS), and overall survival (OS).
II. Evaluate the magnitude of change in tumor infiltrating T cells, PD-1 expression, and the Th1/Th2 ratio in prostate cancer tumor tissue before and after immunotherapy and correlate it with the clinical outcomes of response, PFS, and OS.
OUTLINE:
Patients receive pembrolizumab intravenously (IV) over 30 minutes every 3 weeks. Treatment repeats every 3 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity. Beginning at least 1 week after pembrolizumab, patients receive HER2Bi-armed activated T cells IV over 5-15 minutes 2 times a week for 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
- Conditions
- Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma, Prostate Carcinoma Metastatic in the Bone, PSA Progression, Stage IV Prostate Adenocarcinoma AJCC v7
- Being tested
- HER2Bi-Armed Activated T Cells, Laboratory Biomarker Analysis, Pembrolizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HER2Bi-Armed Activated T CellsBiological
Also called Anti-CD3 x Anti-Her2/neu Bispecific Antibody-Armed Activated T Cells, HER2Bi-Armed ATCs
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (pembrolizumab, HER2Bi-armed activated T cells) | Experimental | Patients receive pembrolizumab IV over 30 minutes every 3 weeks. Treatment repeats every 3 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity. Beginning at least 1 week after pembrolizumab, patients receive HER2Bi-armed activated T cells IV over 5-15 minutes 2 times a week for 4 weeks in the absence of disease progression or unacceptable toxicity. Receives: Biological: HER2Bi-Armed Activated T Cells; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
Percentage of patients achieving clinical progression-free interval at 6 months from study registration
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2018
- Study start7 Jun 2018
- Primary completion20 Jan 2021
- Study completion7 Nov 2022
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Castration Levels of TestosteroneStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barbara Ann Karmanos Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Abhinav Deol, Barbara Ann Karmanos Cancer Institute
- Investigators
- Abhinav Deol, M.D., Principal investigator, Barbara Ann Karmanos Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03406858
- Sponsor's protocol ID
- 2015-135
- Other IDs
- NCI-2017-02156, 2015-135, P30CA022453
- Status last verified
- Apr 2023
- First submitted
- 8 Dec 2017
- Last updated
- 3 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Vaishampayan UN, Heilbrun L, Vaishampayan N, Harper FWK, Shi D, Smith D, Green K, Guru K, Li Q, Kuettel M, Chatta G, Maier J, Dickow B, Moore TF, George S. Phase II Trial of Concurrent Nivolumab and Radiation Therapy for Muscle-Invasive Bladder Cancer of Older or Chemotherapy-Ineligible Patients. Int J Radiat Oncol Biol Phys. 2024 Apr 1;118(5):1472-1480. doi: 10.1016/j.ijrobp.2023.11.024. Epub 2023 Nov 18.
PubMed 37981040
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Immune Checkpoint Inhibitor With Anti-CD3 x Anti-HER2 Bispecific Antibody Armed Activated T Cells in Metastatic Castrate Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT03406858
- Acronym / sponsor ID
- 2015-135
- Conditions
- Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma, Prostate Carcinoma Metastatic in the Bone, PSA Progression, Stage IV Prostate Adenocarcinoma AJCC v7
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Barbara Ann Karmanos Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 7 Jun 2018 (actual)
- Primary completion
- 20 Jan 2021 (actual)
- Study completion
- 7 Nov 2022 (actual)
- First posted
- 23 Jan 2018 (actual)
- Results
- Posted 15 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well pembrolizumab and HER2Bi-armed activated T cells work in treating patients with castration resistant prostate cancer that has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. HER2Bi-armed activated T cells are made using T cells and may target and kill cancer cells. Giving pembrolizumab and HER2Bi-armed activated T cells may work better in treating patients with castration resistant prostate cancer.
Detailed description
PRIMARY OBJECTIVES:
- To estimate the clinical efficacy of 8 infusions of HER2 HER2Bi-armed activated T cells (BATs) (up to 10^10/infusion) twice per week for 4 weeks in combination with pembrolizumab once every 3 weeks starting with one dose 3 weeks before the 1st BATs infusion, by assessing the percentage of patients free of clinical progression at 6 months after registration.
SECONDARY OBJECTIVES:
- Evaluate phenotype, cytokine profiles and IFN-gamma enzyme-linked immunosorbent spots (ELISpots), cytotoxicity and antibodies directed at laboratory prostate cancer cell lines for proof of principle of immune system activation and to correlate with clinical outcomes of response, progression free survival (PFS), and overall survival (OS).
II. Evaluate the magnitude of change in tumor infiltrating T cells, PD-1 expression, and the Th1/Th2 ratio in prostate cancer tumor tissue before and after immunotherapy and correlate it with the clinical outcomes of response, PFS, and OS.
OUTLINE:
Patients receive pembrolizumab intravenously (IV) over 30 minutes every 3 weeks. Treatment repeats every 3 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity. Beginning at least 1 week after pembrolizumab, patients receive HER2Bi-armed activated T cells IV over 5-15 minutes 2 times a week for 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (pembrolizumab, HER2Bi-armed activated T cells) | Experimental | Biological: HER2Bi-Armed Activated T Cells, Other: Laboratory Biomarker Analysis, Biological: PembrolizumabPatients receive pembrolizumab IV over 30 minutes every 3 weeks. Treatment repeats every 3 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity. Beginning at least 1 week after pembrolizumab, patients receive HER2Bi-armed activated T cells IV over 5-15 minutes 2 times a week for 4 weeks in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Be willing and able to provide written informed consent/assent for the trial
- Have histologically confirmed prostate adenocarcinoma, with metastases
- Progression by either PSA, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for measurable disease or new areas of metastases on bone scan or symptom progression related to prostate cancer despite castrate levels of testosterone; (level < 50 ng/ml)
- Be agreeable to continue to maintain castrate levels of testosterone
- At least 2 weeks should have elapsed since any immunosuppressive therapy
Key exclusion criteria (19 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (> 10 mg of prednisone daily or equivalent steroid doses) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Has a known history of active TB (Bacillus tuberculosis)
- Has hypersensitivity to pembrolizumab or any of its excipients
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or has not recovered (i.e. =< grade 1 or at baseline) from adverse events due to agents administered earlier; Note: Subjects with =<grade 2 neuropathy are an exception to this criterion and may qualify for the study
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 |
|---|---|---|
| HER2Bi-Armed Activated T CellsAlso: Anti-CD3 x Anti-Her2/neu Bispecific Antibody-Armed Activated T Cells, HER2Bi-Armed ATCsGiven IV | Biological | Treatment (pembrolizumab, HER2Bi-armed activated T cells) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (pembrolizumab, HER2Bi-armed activated T cells) |
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Biological | Treatment (pembrolizumab, HER2Bi-armed activated T cells) |
Primary outcome
Progression-free Survival
Time frame: Up to 6 months
Percentage of patients achieving clinical progression-free interval at 6 months from study registration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37981040Vaishampayan UN, Heilbrun L, Vaishampayan N, Harper FWK, Shi D, Smith D, Green K, Guru K, Li Q, Kuettel M, Chatta G, Maier J, Dickow B, Moore TF, George S. Phase II Trial of Concurrent Nivolumab and Radiation Therapy for Muscle-Invasive Bladder Cancer of Older or Chemotherapy-Ineligible Patients. Int J Radiat Oncol Biol Phys. 2024 Apr 1;118(5):1472-1480. doi: 10.1016/j.ijrobp.2023.11.024. Epub 2023 Nov 18.
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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.
Abhinav Deol, M.D. principal investigator
Barbara Ann Karmanos Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HER2Bi-Armed Activated T Cells, Laboratory Biomarker Analysis and Pembrolizumab in people with Castration Levels of Testosterone and Castration-Resistant Prostate Carcinoma, run by Barbara Ann Karmanos Cancer Institute 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 23 inclusion and 19 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 3 May 2023. 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 phase mean?
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 15 Nov 2022). 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?
Progression-free Survival (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03406858, which also lists 1 linked publication.
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 3 May 2023.