Pilot Study of PLX3397 in Patients With Advanced Castration-Resistant Prostate Cancer (CRPC)
Study Details
Study Description
Brief Summary
The main objective of this study is to evaluate the effects of PLX3397 on male subjects with CRPC.
Secondary objectives include evaluating the safety and tolerability of PLX3397 and the anti-tumor effects that PLX3397 has on the the subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PLX3397 Participants will take daily oral dose of PLX3397 for 28 day cycles. Participants will continue to take PLX3397 until disease progression or toxicity. |
Drug: PLX3397
Capsules administered twice daily, continuous dosing. Subjects will take PLX3397 at 1000 mg/day.
|
Outcome Measures
Primary Outcome Measures
- Summary of High Circulating Tumor Cell Count Number In Men With Radiographically Progressive Castration-Resistant Prostate Cancer and High Circulating Tumor Cells [See measure description for time frame.]
Effects of PLX3397 on CTC number in men with radiographically progressive CRPC and high CTC counts (≥10 CTCs/7.5 mL of blood using CellSearch Assay) CTC counts were to be evaluated at the following time points: Screening, Baseline, every 4 weeks after treatment initiation, and at Safety Follow-up. Radiographic tumor evaluation were to be performed every 8 weeks. Progression at the first reassessment required a confirmatory scan at a minimum of 6 weeks later, and treatment with study medication was to continue until the progression had been confirmed.
Secondary Outcome Measures
- Number of Participants Reporting Treatment-Related Adverse Events by System Organ Class and Preferred Term [Assessed from first dose through at least 4 weeks after the last dose.]
- Number of Participants Reporting Treatment-Emergent Adverse Events by Worst Severity Grade [Assessed from first dose through at least 4 weeks after the last dose.]
Adverse events (AEs) were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0, where 1=mild, 2=moderate, 3=severe, 4=life-threatening, and 5=death related to AE.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed prostate cancer, currently with objective progressive disease.
-
Castrate level of testosterone (<50 ng/dL).
-
Baseline circulating tumor cell (CTC) count ≥10/7.5 mL blood.
-
Archival tumor tissue (unstained sections, paraffin block, or frozen tumor tissue) has been requisitioned for shipment to the central laboratory.
-
Karnofsky performance status of 80-100.
-
Adequate organ and marrow function.
Exclusion Criteria:
-
The subject has received:
-
Any systemic chemotherapy (including investigational agents) within 4 weeks (with the exception of nitrosoureas/mitomycin C within 6 weeks), of the first dose of study treatment, OR
-
Biological agents (antibodies, immune modulators, cytokines, or vaccines) within 6 weeks of the first dose of study treatment, OR
-
Hormonal anticancer therapy (not including LHRH agonists or antagonists) within 2 weeks before the first dose of study treatment. Specific restrictions on prior hormonal and other anticancer treatments are detailed in inclusion criterion, OR
-
Small-molecular kinase inhibitors or any other type of investigational agent within 4 weeks before the first dose of study treatment or 5 half-lives of the compound or active metabolite, whichever is shorter.
-
The subject has received drugs used to control loss of bone mass (e.g., bisphosphonates) within 4 weeks prior to the first dose of study treatment.
-
The subject has symptomatic or uncontrolled brain metastasis or epidural disease requiring current treatment including steroids and anti-convulsants.
-
The subject has a corrected QT interval calculated by the Fridericia formula (QTcF)
450 ms at screening.
-
The subject has uncontrolled or significant intercurrent illness including, but not limited to, the following conditions:
-
Cardiovascular disorders such as symptomatic congestive heart failure (CHF), *Uncontrolled hypertension
-
Unstable angina pectoris, clinically-significant cardiac arrhythmias
-
History of stroke (including transient ischemic attack [TIA] or other ischemic event) within 6 months of study treatment
-
Myocardial infarction within 6 months of study treatment
-
History of thromboembolic event requiring therapeutic anticoagulation within 6 months of study treatment or main portal vein or vena cava thrombosis or occlusion.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 2 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Daiichi Sankyo, Inc.
- Plexxikon
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PLX108-06
Study Results
Participant Flow
| Recruitment Details | A total of 6 participants received study drug at 2 clinic sites. |
|---|---|
| Pre-assignment Detail | A total of 20 participants were planned to be enrolled at approximately 2 to 4 clinic sites. |
| Arm/Group Title | PLX3397 |
|---|---|
| Arm/Group Description | Participants who received a daily oral dose of PLX3397 for 28 day cycles and continued on therapy until disease progression or toxicity. |
| Period Title: Overall Study | |
| STARTED | 6 |
| COMPLETED | 0 |
| NOT COMPLETED | 6 |
Baseline Characteristics
| Arm/Group Title | PLX3397 |
|---|---|
| Arm/Group Description | Participants who received a daily oral dose of PLX3397 for 28 day cycles and continued on therapy until disease progression or toxicity. |
| Overall Participants | 6 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
71.0
(7.24)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
6
100%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
2
33.3%
|
| White |
4
66.7%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
6
100%
|
Outcome Measures
| Title | Summary of High Circulating Tumor Cell Count Number In Men With Radiographically Progressive Castration-Resistant Prostate Cancer and High Circulating Tumor Cells |
|---|---|
| Description | Effects of PLX3397 on CTC number in men with radiographically progressive CRPC and high CTC counts (≥10 CTCs/7.5 mL of blood using CellSearch Assay) CTC counts were to be evaluated at the following time points: Screening, Baseline, every 4 weeks after treatment initiation, and at Safety Follow-up. Radiographic tumor evaluation were to be performed every 8 weeks. Progression at the first reassessment required a confirmatory scan at a minimum of 6 weeks later, and treatment with study medication was to continue until the progression had been confirmed. |
| Time Frame | See measure description for time frame. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The study was discontinued and the primary outcome measure was not evaluated. Consequently, no efficacy was evaluated and only safety results are reported. Raw data collected but no efficacy analysis was performed/reported. |
| Arm/Group Title | PLX3397 |
|---|---|
| Arm/Group Description | Participants who received a daily oral dose of PLX3397 for 28 day cycles and continued on therapy until disease progression or toxicity. |
| Measure Participants | 0 |
| Title | Number of Participants Reporting Treatment-Related Adverse Events by System Organ Class and Preferred Term |
|---|---|
| Description | |
| Time Frame | Assessed from first dose through at least 4 weeks after the last dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Adverse events were assessed in the Safety Population. |
| Arm/Group Title | PLX3397 |
|---|---|
| Arm/Group Description | Participants who received a daily oral dose of PLX3397 for 28 day cycles and continued on therapy until disease progression or toxicity. |
| Measure Participants | 6 |
| Anaemia |
1
16.7%
|
| Thrombocytopenia |
1
16.7%
|
| Constipation |
2
33.3%
|
| Diarrhoea |
2
33.3%
|
| Nausea |
4
66.7%
|
| Fatigue |
3
50%
|
| Mucosal inflammation |
1
16.7%
|
| Alanine aminotransferase increased |
1
16.7%
|
| Aspartate aminotransferase increased |
1
16.7%
|
| Blood creatinine phosphokinase increased |
1
16.7%
|
| Blood glucose increased |
1
16.7%
|
| Blood sodium increased |
1
16.7%
|
| Lipase increased |
1
16.7%
|
| Decreased appetite |
3
50%
|
| Pain in extremity |
1
16.7%
|
| Dyspnoea |
1
16.7%
|
| Title | Number of Participants Reporting Treatment-Emergent Adverse Events by Worst Severity Grade |
|---|---|
| Description | Adverse events (AEs) were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0, where 1=mild, 2=moderate, 3=severe, 4=life-threatening, and 5=death related to AE. |
| Time Frame | Assessed from first dose through at least 4 weeks after the last dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Adverse events were assessed in the Safety Population. |
| Arm/Group Title | NCI CTCAE Grade 1 | NCI CTCAE Grade 2 | NCI CTCAE Grade 3 | NCI CTCAE Grade 4 | NCI CTCAE Grade 5 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received PLX3397 and experienced a Grade 1 treatment-emergent adverse event. | Participants who received PLX3397 and experienced a Grade 2 treatment-emergent adverse event. | Participants who received PLX3397 and experienced a Grade 3 treatment-emergent adverse event. | Participants who received PLX3397 and experienced a Grade 4 treatment-emergent adverse event. | Participants who received PLX3397 and experienced a Grade 5 treatment-emergent adverse event. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Anaemia |
0
0%
|
1
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Thrombocytopenia |
1
16.7%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Constipation |
2
33.3%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Diarrhoea |
2
33.3%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Nausea |
4
66.7%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Fatigue |
1
16.7%
|
2
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Mucosal inflammation |
1
16.7%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Pyrexia |
0
0%
|
1
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Oedema |
1
16.7%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Oedema peripheral |
1
16.7%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Pain |
2
33.3%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Influenza |
0
0%
|
0
NaN
|
1
NaN
|
0
NaN
|
0
NaN
|
| Pneumonia |
0
0%
|
0
NaN
|
1
NaN
|
0
NaN
|
0
NaN
|
| Fall |
0
0%
|
0
NaN
|
1
NaN
|
0
NaN
|
0
NaN
|
| ALT increased |
0
0%
|
0
NaN
|
1
NaN
|
0
NaN
|
0
NaN
|
| AST increased |
0
0%
|
0
NaN
|
1
NaN
|
0
NaN
|
0
NaN
|
| Blood CPK increased |
0
0%
|
0
NaN
|
1
NaN
|
0
NaN
|
0
NaN
|
| Lipase increased |
0
0%
|
0
NaN
|
1
NaN
|
0
NaN
|
0
NaN
|
| Blood glucose increased |
1
16.7%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Blood sodium increased |
1
16.7%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Decreased appetite |
3
50%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Musculoskeletal pain |
1
16.7%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Pain in extremity |
0
0%
|
0
NaN
|
1
NaN
|
0
NaN
|
0
NaN
|
| Peripheral sensory neuropathy |
1
16.7%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Spinal cord disorder |
1
16.7%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Nocturia |
1
16.7%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Urinary retention |
0
0%
|
1
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Pollakiuria |
2
33.3%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Dyspnoea |
1
16.7%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
Adverse Events
| Time Frame | Adverse events were collected from after first dose to 28 days after last dose. | |
|---|---|---|
| Adverse Event Reporting Description | Adverse events that emerge (or worsen) from after the first dose of study drug and within 28 days after last dose. | |
| Arm/Group Title | PLX3397 | |
| Arm/Group Description | Participants who received a daily oral dose of PLX3397 for 28 day cycles and continued on therapy until disease progression or toxicity. | |
All Cause Mortality |
||
| PLX3397 | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | |
Serious Adverse Events |
||
| PLX3397 | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/6 (33.3%) | |
| Infections and infestations | ||
| Influenza | 1/6 (16.7%) | |
| Pneumonia | 1/6 (16.7%) | |
| Injury, poisoning and procedural complications | ||
| Fall | 1/6 (16.7%) | |
| Musculoskeletal and connective tissue disorders | ||
| Pain in extremity | 1/6 (16.7%) | |
| Renal and urinary disorders | ||
| Urinary retention | 1/6 (16.7%) | |
Other (Not Including Serious) Adverse Events |
||
| PLX3397 | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 1/6 (16.7%) | |
| Thrombocytopenia | 1/6 (16.7%) | |
| Gastrointestinal disorders | ||
| Constipation | 2/6 (33.3%) | |
| Diarrhoea | 2/6 (33.3%) | |
| Nausea | 4/6 (66.7%) | |
| General disorders | ||
| Fatigue | 3/6 (50%) | |
| Mucosal inflammation | 1/6 (16.7%) | |
| Oedema | 1/6 (16.7%) | |
| Oedema peripheral | 1/6 (16.7%) | |
| Pain | 2/6 (33.3%) | |
| Pyrexia | 1/6 (16.7%) | |
| Infections and infestations | ||
| Influenza | 1/6 (16.7%) | |
| Pneumonia | 1/6 (16.7%) | |
| Injury, poisoning and procedural complications | ||
| Fall | 1/6 (16.7%) | |
| Investigations | ||
| Alanine aminotransferase increased | 1/6 (16.7%) | |
| Aspartate aminotransferase increased | 1/6 (16.7%) | |
| Blood creatinine phosphokinase increased | 1/6 (16.7%) | |
| Blood glucose increased | 1/6 (16.7%) | |
| Blood sodium increased | 1/6 (16.7%) | |
| Lipase increased | 1/6 (16.7%) | |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 3/6 (50%) | |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal pain | 1/6 (16.7%) | |
| Pain in extremity | 1/6 (16.7%) | |
| Nervous system disorders | ||
| Peripheral sensory neuropathy | 1/6 (16.7%) | |
| Spinal cord disorder | 1/6 (16.7%) | |
| Renal and urinary disorders | ||
| Nocturia | 1/6 (16.7%) | |
| Pollakiuria | 2/6 (33.3%) | |
| Urinary retention | 1/6 (16.7%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnoea | 1/6 (16.7%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Daiichi Sankyo Inc. |
| Phone | 908-992-6400 |
| CTRinfo@dsi.com |
- PLX108-06