Stage I Prostate AdenocarcinomaPhase 1NCT02472275
PLX3397, Radiation Therapy, and Antihormone Therapy in Treating Patients With Intermediate- or High-Risk Prostate Cancer
A Phase 1 study testing Antiandrogen Therapy, Laboratory Biomarker Analysis and Multitargeted Tyrosine Kinase Inhibitor PLX3397 in people with Stage I Prostate Adenocarcinoma and Stage II Prostate Adenocarcinoma, run by Barbara Ann Karmanos Cancer Institute at 3 sites in United States.
Trial summary
This phase I trial studies the side effects and best dose of multitargeted tyrosine kinase inhibitor PLX3397 (PLX3397) when given together with radiation therapy and antihormone therapy in treating patients with prostate cancer that is at intermediate or high risk of spreading. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Stage I Prostate Adenocarcinoma, Stage II Prostate Adenocarcinoma, Stage III Prostate Adenocarcinoma
- What is being tested?
- Antiandrogen Therapy, Laboratory Biomarker Analysis and Multitargeted Tyrosine Kinase Inhibitor PLX3397
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 3 sitesUnited States
- Study dates
- Jun 2015to 5 Aug 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically confirmed diagnosis of prostate adenocarcinoma
- Must have confirmed viable archival prostate biopsy tissue available as per Section 8.1 (this will be collected for patients going on study after the MTD has been reached
- Intermediate or high risk prostate cancer patients who are candidates for radiation therapy:
- Gleason >7 or
- Clinical or pathological > T2b disease or
- PSA > 10 ng/mL
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- No evidence of metastatic disease by clinical and radiological staging
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
- No standard contraindications to radiation therapy including prior significant radiation therapy, inflammatory bowel disease, irritable bowel syndrome or collagen vascular disease
- Prior history of up to 8 weeks of androgen deprivation therapy defined as lutenizing-hormone releasing hormone (LHRH) or other medical castration therapy prior to registration is acceptable. This will be in addition to the 6 months of ADT on study.
- Life expectancy of at least 3 months
- Adequate hematologic, hepatic, and renal function as defined by:
- Absolute neutrophil count ≥ 1.5 × 109/L
- Hemoglobin > 10 g/dL
- Platelet count ≥ 100 × 109/L
- AST and ALT ≤ upper limit of normal (ULN)
- TBil and DBil ≤ ULN with an exception of patients with confirmed Gilbert's syndrome. For patients with confirmed Gilbert's syndrome, the TBil should be ≤ 1.5 × ULN
- Serum creatinine ≤ 1.5 × ULN
- Must have ability to take oral medication
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
- Ability to understand and willingness to sign a written informed consent document
- Willingness to be treated with radiation therapy and androgen deprivation Therapy
Who cannot join
- Investigational drug use within 28 days of the first dose of PLX3397 or concurrently
- At Screening QTcF ≥450 msec
- Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results
- Refractory nausea and vomiting, malabsorption, biliary shunt, or significant bowel resection that would preclude adequate absorption of study drug
- Known active or chronic human immunodeficiency virus (HIV) or hepatitis C virus (HCV) infection, or positive hepatitis B (Hep B) surface antigen. Prior hepatitis infection that has been treated with highly effective therapy with no evidence of residual infection and with normal liver function (ALT, AST, total and direct bilirubin ≤ ULN) is allowed.
- Hepatobiliary diseases including biliary tract diseases, autoimmune hepatitis, inflammation, fibrosis, cirrhosis of liver caused by viral, alcohol, or genetic reasons. Gilbert's disease is allowed if TBil is ≤ 1.5 × ULN.
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- Active cancer (either concurrent or within the last 3 years) that requires nonsurgical therapy (e.g. chemotherapy or radiation therapy), with the exception of surgically treated basal or squamous cell carcinoma of the skin, or melanoma insitu.
- AST/ALT > 2.5X ULN or >5X ULN in the presence of liver metastases.
- Current treatment with anti-androgen is allowed for a maximum of one month to prevent flare response with ADT
- Concomitant use of acid reducing agents (e.g., proton pump inhibitors, H2 receptor antagonists, antacids)
- Concomitant use of strong and moderate CYP3A4 inhibitors and inducers
- Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of the study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Karmanos Cancer Institute at McLaren Northern Michigan - Petoskey Radiation Oncology
Petoskey, Michigan, 49770
Karmanos Cancer Institute at McLaren Northern Michigan- Petoskey Medical Oncology
Petoskey, Michigan, 49770
About this study
Official title: Targeting the Prostatic Tumor Microenvironment With PLX3397, a Tumor-Associated Macrophage Inhibitor in Men With Unfavorable Risk Prostate Cancer Undergoing Radiation Therapy and Androgen Deprivation Therapy
This phase I trial studies the side effects and best dose of multitargeted tyrosine kinase inhibitor PLX3397 (PLX3397) when given together with radiation therapy and antihormone therapy in treating patients with prostate cancer that is at intermediate or high risk of spreading. Multitargeted tyrosine kinase inhibitor PLX3397 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth, and may also help the radiation therapy work better. Radiation therapy uses high-energy x-rays to kill tumor cells. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as leuprolide acetate, goserelin acetate, or degarelix, may lessen the amount of androgens made by the body. Giving multitargeted tyrosine kinase inhibitor PLX3397 with radiation therapy and antihormone therapy may be a better treatment for prostate cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To conduct a phase I, dose escalation trial with a primary objective of establishing the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT).
SECONDARY OBJECTIVES:
- To assess the effects of radiation therapy (RT), androgen deprivation therapy (ADT), and PLX3397 (at its MTD) on tumor-associated macrophages (TAMs) in the prostate biopsy after treatment.
OUTLINE: This is a dose-escalation study of multitargeted tyrosine kinase inhibitor PLX3397.
Patients receive multitargeted tyrosine kinase inhibitor PLX3397 orally (PO) twice daily (BID) for 6 months, undergo radiation therapy for 2 months daily (Monday-Friday) beginning at month 3, and undergo ADT with leuprolide acetate, goserelin acetate, or degarelix injections in any month.
After completion of study treatment, patients are followed up at 20-30 days and then every 12 weeks thereafter.
- Conditions
- Stage I Prostate Adenocarcinoma, Stage II Prostate Adenocarcinoma, Stage III Prostate Adenocarcinoma
- Being tested
- Antiandrogen Therapy, Laboratory Biomarker Analysis, Multitargeted Tyrosine Kinase Inhibitor PLX3397, Radiation Therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antiandrogen TherapyDrug
Also called ADT, Androgen Deprivation Therapy, Anti-androgen Therapy, Anti-androgen Treatment
Undergo ADT with leuprolide acetate, goserelin acetate, or degarelix
Laboratory Biomarker AnalysisOther
Correlative studies
Multitargeted Tyrosine Kinase Inhibitor PLX3397Drug
Also called PLX3397
Given PO
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Irradiate, Irradiated, Irradiation
Undergo radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| Treatment (PLX3397, radiation therapy, ADT) | Experimental | Patients receive multitargeted tyrosine kinase inhibitor PLX3397 PO BID for 6 months, undergo radiation therapy for 2 months daily (Monday-Friday) beginning at month 3, and undergo ADT with leuprolide acetate, goserelin acetate, or degarelix injections in any month. Receives: Drug: Antiandrogen Therapy; Other: Laboratory Biomarker Analysis; Drug: Multitargeted Tyrosine Kinase Inhibitor PLX3397; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Grade of specific types of toxicity
Frequency distributions will be generated by dose level, and overall.
Measured: Up to 30 days after end of study treatment
MTD of multitargeted tyrosine kinase inhibitor PLX3397, determined according to incidence of DLT
Measured: 4 months
Secondary outcomes (3)
Change in metabolic syndrome parameters
Descriptive statistics will be used to summarize the 7 metabolic syndrome parameters), and changes in them. These statistics will be calculated only for patients treated at the MTD, where the correlatives are measured, and will be generated for all 12 MTD patients combined, and separately by MTD randomization arm.
Measured: Baseline to month 7
Change in PSA levels
PSA levels (and their change) will be tabulated for individual patients, regardless of dose level. Descriptive statistics will be used to summarize PSA, and changes in it. Serial PSA levels will be displayed using spaghetti plots, and changes in PSA using waterfall plots.
Measured: Baseline to up to month 7
Change TAM levels as measured by immunohistochemistry
Frequency distributions will be generated for patients treated at the MTD. Descriptive statistics will be used to summarize all markers, and changes in them.
Measured: Baseline to month 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2015 (estimated)
- Study startJun 2015
- Primary completion5 Aug 2019
- Study completion5 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage I Prostate AdenocarcinomaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 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, Elisabeth Heath, Barbara Ann Karmanos Cancer Institute
- Investigators
- Elisabeth I. Heath, M.D., Principal investigator, Barbara Ann Karmanos Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02472275
- Sponsor's protocol ID
- 2014-075
- Other IDs
- NCI-2015-00742, 1501013723, 2014-075, P30CA022453
- Status last verified
- Oct 2020
- First submitted
- 11 Jun 2015
- Last updated
- 6 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting the Prostatic Tumor Microenvironment With PLX3397, a Tumor-Associated Macrophage Inhibitor in Men With Unfavorable Risk Prostate Cancer Undergoing Radiation Therapy and Androgen Deprivation Therapy
- ClinicalTrials.gov ID
- NCT02472275
- Acronym / sponsor ID
- 2014-075
- Conditions
- Stage I Prostate Adenocarcinoma, Stage II Prostate Adenocarcinoma, Stage III Prostate Adenocarcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Barbara Ann Karmanos Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 2015
- Primary completion
- 5 Aug 2019 (actual)
- Study completion
- 5 Aug 2019 (actual)
- First posted
- 15 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and best dose of multitargeted tyrosine kinase inhibitor PLX3397 (PLX3397) when given together with radiation therapy and antihormone therapy in treating patients with prostate cancer that is at intermediate or high risk of spreading. Multitargeted tyrosine kinase inhibitor PLX3397 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth, and may also help the radiation therapy work better. Radiation therapy uses high-energy x-rays to kill tumor cells. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as leuprolide acetate, goserelin acetate, or degarelix, may lessen the amount of androgens made by the body. Giving multitargeted tyrosine kinase inhibitor PLX3397 with radiation therapy and antihormone therapy may be a better treatment for prostate cancer.
Detailed description
PRIMARY OBJECTIVES:
- To conduct a phase I, dose escalation trial with a primary objective of establishing the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT).
SECONDARY OBJECTIVES:
- To assess the effects of radiation therapy (RT), androgen deprivation therapy (ADT), and PLX3397 (at its MTD) on tumor-associated macrophages (TAMs) in the prostate biopsy after treatment.
OUTLINE: This is a dose-escalation study of multitargeted tyrosine kinase inhibitor PLX3397.
Patients receive multitargeted tyrosine kinase inhibitor PLX3397 orally (PO) twice daily (BID) for 6 months, undergo radiation therapy for 2 months daily (Monday-Friday) beginning at month 3, and undergo ADT with leuprolide acetate, goserelin acetate, or degarelix injections in any month.
After completion of study treatment, patients are followed up at 20-30 days and then every 12 weeks thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (PLX3397, radiation therapy, ADT) | Experimental | Drug: Antiandrogen Therapy, Other: Laboratory Biomarker Analysis, Drug: Multitargeted Tyrosine Kinase Inhibitor PLX3397, Radiation: Radiation TherapyPatients receive multitargeted tyrosine kinase inhibitor PLX3397 PO BID for 6 months, undergo radiation therapy for 2 months daily (Monday-Friday) beginning at month 3, and undergo ADT with leuprolide acetate, goserelin acetate, or degarelix injections in any month. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Pathologically confirmed diagnosis of prostate adenocarcinoma
- Must have confirmed viable archival prostate biopsy tissue available as per Section 8.1 (this will be collected for patients going on study after the MTD has been reached
- Intermediate or high risk prostate cancer patients who are candidates for radiation therapy:
- Gleason >7 or
- Clinical or pathological > T2b disease or
Key exclusion criteria (12 listed)
- Investigational drug use within 28 days of the first dose of PLX3397 or concurrently
- At Screening QTcF ≥450 msec
- Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results
- Refractory nausea and vomiting, malabsorption, biliary shunt, or significant bowel resection that would preclude adequate absorption of study drug
- Known active or chronic human immunodeficiency virus (HIV) or hepatitis C virus (HCV) infection, or positive hepatitis B (Hep B) surface antigen. Prior hepatitis infection that has been treated with highly effective therapy with no evidence of residual infection and with normal liver function (ALT, AST, total and direct bilirubin ≤ ULN) is allowed.
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 |
|---|---|---|
| Antiandrogen TherapyAlso: ADT, Androgen Deprivation Therapy, Anti-androgen Therapy, Anti-androgen TreatmentUndergo ADT with leuprolide acetate, goserelin acetate, or degarelix | Drug | Treatment (PLX3397, radiation therapy, ADT) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (PLX3397, radiation therapy, ADT) |
| Multitargeted Tyrosine Kinase Inhibitor PLX3397Also: PLX3397Given PO | Drug | Treatment (PLX3397, radiation therapy, ADT) |
| Radiation TherapyAlso: Cancer Radiotherapy, Irradiate, Irradiated, IrradiationUndergo radiation therapy | Radiation | Treatment (PLX3397, radiation therapy, ADT) |
Primary outcome
Grade of specific types of toxicity
Time frame: Up to 30 days after end of study treatment
Frequency distributions will be generated by dose level, and overall.
MTD of multitargeted tyrosine kinase inhibitor PLX3397, determined according to incidence of DLT
Time frame: 4 months
3 secondary outcomes
Change in metabolic syndrome parameters
Time frame: Baseline to month 7
Change in PSA levels
Time frame: Baseline to up to month 7
Change TAM levels as measured by immunohistochemistry
Time frame: Baseline to month 2
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2020.
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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.
Elisabeth I. Heath, M.D. principal investigator
Barbara Ann Karmanos Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Antiandrogen Therapy, Laboratory Biomarker Analysis and Multitargeted Tyrosine Kinase Inhibitor PLX3397 in people with Stage I Prostate Adenocarcinoma and Stage II Prostate Adenocarcinoma, run by Barbara Ann Karmanos Cancer Institute at 3 sites 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 22 inclusion and 12 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 6 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Grade of specific types of toxicity (time frame: Up to 30 days after end of study treatment). The study lists 2 primary outcomes in all. 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 6 Oct 2020.