Status:
COMPLETED
ProSTAR: A Study Evaluating CPI-1205 in Patients With Metastatic Castration Resistant Prostate Cancer
Lead Sponsor:
Constellation Pharmaceuticals
Conditions:
Metastatic Castration Resistant Prostate Cancer (mCRPC)
Eligibility:
MALE
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
This was an open-label Phase 1b/2 study involving oral administration of CPI-1205 in combination with either enzalutamide or abiraterone/prednisone in male patients with metastatic Castration-Resistan...
Detailed Description
Study CPI-1205-201 was a Phase 1b/2, multi-center, open-label study of CPI-1205 alone and with cobicistat in subjects with mCRPC in combination with either enzalutamide or abiraterone/prednisone. The ...
Eligibility Criteria
Inclusion
- PHASE 1b DOSE ESCALATION
- Inclusion Criteria for Phase 1b Dose Escalation
- Patients must meet all the following criteria to be enrolled in this study:
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- Life expectancy of at least 12 weeks
- Histologically or cytologically confirmed adenocarcinoma of the prostate (pure small cell carcinoma excluded)
- Documented metastatic disease
- Must have undergone bilateral orchiectomy (surgical castration) or willing to continue gonadotropin-releasing hormone (GnRH) analog or antagonist (medical castration)
- Serum testosterone \< 50 ng/dL
- Progressive disease in the setting of medical or surgical castration (i.e., Castration-resistant Prostate Cancer \[CRPC\]) as assessed by the investigator and includes at least one of the following:
- Evidence of progression as measured by PSA increase of ≥ 25% and an absolute increase of ≥ 2 ng/mL in \< 6 months from end of last therapy prior to enrollment and/or
- Soft tissue disease progression as per Response Evaluation Criteria in Solid Tumors (RECIST) and/or
- Bone disease progression defined by two or more new lesions on bone scan
- Bisphosphonate or denosumab therapy allowed provided dose has been stable for at least 4 weeks prior to Day 1 of treatment
- Prior treatment:
- Prior treatment for metastatic CRPC (mCRPC) must have included at least one line with a second-generation androgen inhibitor (e.g., abiraterone, enzalutamide, apalutamide, daralutamide)
- Prior chemotherapy permitted when administered in the metastatic hormone-sensitive prostate cancer setting. In addition, up to one line of chemotherapy is allowed in the mCRPC setting.
- Prior treatment with sipuleucel-T, radium-223, or other non-chemotherapy based treatments for mCRPC (e.g., olaparib, pembrolizumab) is allowed.
- Recovery from recent surgery, radiotherapy, chemotherapy or other anti-cancer treatment to baseline or ≤ Grade 1 (other than alopecia)
- Demonstrate adequate organ function as defined in the table below; all Screening labs obtained within 28 days prior to Day 1 of treatment.
- Patients who have not undergone a bilateral orchiectomy and have a female partner of childbearing potential must use an adequate barrier method of contraception during study treatment and for 90 days after receiving the last dose of CPI-1205
- Willing to provide access to archival tumor tissue for research purposes
- Ability to swallow and retain oral medications
- Ability to understand and willingness to sign an IRB approved written informed consent form (ICF) and authorization permitting release of personal health information including genetic testing relevant to cancer.
- Able to comply with study visit schedule and assessments
- Exclusion Criteria for Phase 1b Dose Escalation
- Patients who meet any of the following criteria will not be enrolled in the study:
- Known symptomatic brain metastases
- Treatment with any of the following for prostate cancer within the indicated timeframe prior to Day 1 of treatment
- First generation: AR antagonists (e.g., bicalutamide, nilutamide, flutamide) within 4 weeks
- 5 alpha reductase inhibitors, ketoconazole, estrogens (including diethylstilbesterol \[DES\]), or progesterones within 2 weeks
- Chemotherapy within 3 weeks
- Biologic therapy within 4 weeks
- Investigational therapy within 3 weeks (or within a time interval less than at least 5 half-lives of the investigational agent \[if known\], whichever is longer).
- Immunotherapy within 4 weeks
- Radionuclide therapy within 4 weeks
- Radiation therapy for the treatment of metastasis within 1 week prior to Day 1 of treatment
- Herbal products that may decrease PSA levels within 4 weeks prior to day 1 of treatment
- Systemic steroids greater than 10 mg of prednisone/prednisolone per day within 4 weeks prior to day 1 of treatment
- Major surgery within 4 weeks prior to Day 1 of treatment
- Planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery
- Structurally unstable bone lesions concerning for impending fracture
- Clinically significant cardiovascular disease including:
- Myocardial infarction (MI)/Stroke within 6 months prior to Day 1 of treatment
- Uncontrolled angina within 3 months
- Congestive heart failure (CHF) with New York Heart Association (NYHA) Class 3 or 4
- History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
- Uncontrolled hypertension (systolic blood pressure (BP) \> 170 mmHg or diastolic BP \> 105 mmHg at screening) despite 2 concomitant antihypertensive therapies
- QT interval corrected by the Fridericia correction formula (QTcF) \> 500 msec on the screening ECG
- Active or symptomatic viral hepatitis or chronic liver disease
- History of unresolved adrenal dysfunction
- GI disorder that negatively affects absorption
- Required treatment with one of the prohibited concomitant medications;
- Achlorhydria, either documented or suspected on the basis of an associated disease (e.g., pernicious anemia, atrophic gastritis, or certain gastric surgical procedures)
- History of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within 12 months prior to Day 1 of treatment, cerebral vascular accident or brain arteriovenous malformation
- Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ bladder cancer, or other cancer for which the patient has been disease-free for at least two years
- Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant psychiatric or neurological disorder, active or uncontrolled infection)
- Patient unwilling or unable to comply with this study protocol
- PHASE 1b: HEAVILY PRETREATED EXPANSION COHORT (HPEC)
- Inclusion Criteria for Phase 1b HPEC
- Patients must meet all the following criteria to be enrolled in this study:
- Age ≥ 18 years
- ECOG Performance Status 0-1
- Life expectancy of at least 12 weeks
- Histologically or cytologically confirmed adenocarcinoma of the prostate (pure small cell carcinoma excluded)
- Documented metastatic disease
- At least 1 measurable lymph node per Prostate Cancer Clinical Trials Working Group 3 (PCWG3)
- Must have undergone bilateral orchiectomy (surgical castration) or willing to continue GnRH analog or antagonist (medical castration)
- Serum testosterone \< 50 ng/dL
- Progressive disease in the setting of medical or surgical castration (i.e., CRPC) as assessed by the investigator and that includes at least 1 of the following:
- Evidence of progression as measured by PSA defined as: PSA at least 2 ng/mL (or PSA at least 1 ng/mL if PSA progression is the only manifestation of progressive disease) and rising PSA by at least 2 consecutive measurements a minimum of 1-week apart and/or
- Soft tissue disease progression as per RECIST 1.1 and/or
- Bone disease progression defined by two or more new lesions on bone scan
- Prior treatment:
- Only 1 prior line of a second-generation androgen inhibitor from a different class than the one chosen for the applicable phase 2 study (the 2 classes are CYP17 inhibitors \[e.g., abiraterone, orteronel\] and AR inhibitors \[e.g., enzalutamide, apalutamide\]). Patient must have progressed after ≥ 24 weeks of treatment with this second generation angrogen inhibitor.
- The last second-generation androgen inhibitor treatment received must not be from the same class as that incorporated in the applicable HPEC; i.e., if the HPEC incorporates enzalutamide, the last second generation androgen inhibitor therapy cannot be enzalutamide, apalutamide, etc.
- Prior chemotherapy for mCRPC must have included at least 1 and no more than 2 prior lines of taxane-based chemotherapy administered in the metastatic hormone-sensitive prostate cancer setting is allowed
- Prior treatment with sipuleucel-T, radium-223, or other non-chemotherapy-based treatments for mCRPC (e.g., olaparib, pembrolizumab, nivolumab) is allowed.
- Recovery from recent surgery, radiotherapy, chemotherapy or other anti-cancer treatment to baseline or ≤ Grade 1 (other than alopecia)
- Demonstrate adequate organ function as defined in the table below; all Screening labs to be obtained within 28 days prior to Day 1 of treatment
- Patients who had not undergone a bilateral orchiectomy and have a female partner of childbearing potential must use an adequate barrier method of contraception during study treatment and for 90 days after receiving the last dose of CPI-1205
- Willing to provide access to archival tumor tissue for research purposes
- Ability to swallow and retain oral medications
- Ability to understand and willingness to sign an IRB approved written ICF and authorization permitting release of personal health information including genetic testing relevant to cancer.
- Able to comply with study visit schedule and assessments
- Exclusion Criteria for Phase 1b HPEC
- Patients meeting any of the following criteria will not be enrolled in the study:
- Known symptomatic brain metastases
- Treatment with any of the following for prostate cancer within the indicated timeframe prior to Day 1 of treatment
- First-generation: AR antagonists (e.g., bicalutamide, nilutamide, flutamide) within 4 weeks
- 5-alpha reductase inhibitors, ketoconazole, estrogens (including DES), or progesterones within 2 weeks
- Chemotherapy within 3 weeks
- Biologic therapy within 4 weeks
- Investigational therapy within 3 weeks (or within a time interval less than at least 5 half-lives of the investigational agent \[if known\], whichever is longer).
- Immunotherapy within 4 weeks
- Radionuclide therapy within 4 weeks
- Radiation therapy for the treatment of metastasis within 1 week prior to Day 1 of treatment
- Herbal products that may decrease PSA levels within 4 weeks prior to Day 1 of treatment
- Systemic steroids greater than 10 mg of prednisone/prednisolone per day within 4 weeks prior to Day 1 of treatment
- Major surgery within 4 weeks prior to Day 1 of treatment
- Structurally unstable bone lesions concerning for impending fracture
- Clinically significant cardiovascular disease including:
- MI/Stroke within 6 months prior to Day 1 of treatment
- Uncontrolled angina within 3 months
- CHF with NYHA Class 3 or 4
- History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
- Uncontrolled hypertension (systolic BP \> 170 mmHg or diastolic BP \> 105 mmHg at screening) despite two concomitant antihypertensive therapies
- QTcF \>500 msec on the screening ECG
- Active or symptomatic viral hepatitis or chronic liver disease
- History of unresolved adrenal dysfunction
- GI disorder that negatively affects absorption
- Required treatment with one of the prohibited concomitant medications
- Achlorhydria, either documented or suspected on the basis of an associated disease (e.g., pernicious anemia, atrophic gastritis, or certain gastric surgical procedures)
- History of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within 12 months prior to day 1 of treatment, cerebral vascular accident or brain arteriovenous malformation
- Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ bladder cancer, or other cancer for which the patient has been disease-free for at least 2 years
- Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant psychiatric or neurological disorder, active or uncontrolled infection)
- Patient unwilling or unable to comply with this study protocol
- PHASE 2
- Phase 2 Inclusion Criteria
- Patients must meet all of the following criteria to be enrolled in this study:
- Age ≥ 18 years
- ECOG Performance Status 0-1
- Life expectancy of at least 12 weeks
- Histologically or cytologically confirmed adenocarcinoma of the prostate (pure small cell carcinoma excluded)
- Documented metastatic disease
- Must have undergone bilateral orchiectomy (surgical castration) or willing to continue GnRH analog or antagonist (medical castration).
- Serum testosterone \<5 0 ng/dL
- Progressive disease in the setting of medical or surgical castration (i.e., CRPC) as assessed by the investigator and that includes at least 1 of the following:
- Evidence of progression as measured by PSA defined as: PSA greater than or equal to 2 ng/mL (or PSA greater than or equal to 1 ng/mL if PSA progression is the only manifestation of progressive disease) and rising PSA by at least 2 consecutive measurements a minimum of 1-week apart and/or
- Soft tissue disease progression as per RECIST 1.1 and/or
- Bone disease progression defined by two or more new lesions on bone scan
- Bisphosphonate or denosumab therapy allowed provided dose has been stable for ≥ 4 weeks prior to Day 1 of treatment.
- Prior treatment:
- Only one prior line of a second-generation androgen inhibitor from a different class than the one chosen for the applicable phase 2 study (the 2 classes are CYP17 inhibitors \[e.g., abiraterone, orteronel\] and AR inhibitors \[e.g., enzalutamide, apalutamide\]). Patient must have progressed after ≥ 24 weeks of treatment with this second generation angrogen inhibitor
- No prior chemotherapy for mCRPC allowed; chemotherapy (including taxane-based) administered in the metastatic hormone-sensitive prostate cancer setting is allowed.
- Prior treatment with sipuleucel-T, radium-223, or other non-chemotherapy based treatments approved by the US FDA for the treatment of mCRPC is allowed; prior treatment with non-chemotherapy based treatments that are not approved for the treatment of mCRPC (e.g., pembrolizumab, ipilimumab, olaparib) are not allowed.
- Recovery from recent surgery, radiotherapy, chemotherapy or other anti-cancer treatment to baseline or ≤ Grade 1 (other than alopecia)
- Demonstrate adequate organ function
- Patients who have not undergone a bilateral orchiectomy and have a female partner of childbearing potential must use an adequate barrier method of contraception during study treatment and for 90 days after receiving the last dose of CPI-1205 (or partner drug in the control arm of any randomized phase 2 trial if the patient does not participate in the crossover).
- Willing to provide access to archival tumor tissue for research purposes, if available
- Ability to swallow and retain oral medications.
- Ability to understand and willingness to sign an IRB approved written ICF and authorization permitting release of personal health information including genetic testing relevant to cancer.
- Able to comply with study visit schedule and assessments
- Phase 2 Exclusion Criteria
- Patients who meet any of the following criteria will not be enrolled in the study:
- Known symptomatic brain metastases
- Treatment with any of the following for prostate cancer within the indicated timeframe prior to Day 1 of treatment
- First-generation AR antagonists (e.g., bicalutamide, nilutamide, flutamide) within 4 weeks
- 5-alpha reductase inhibitors, ketoconazole, estrogens (including DES), or progesterones within 2 weeks
- Chemotherapy within 3 weeks
- Biologic therapy within 4 weeks
- Radionuclide therapy within 4 weeks
- Radiation therapy for the treatment of metastasis within 1 week prior to Day 1 of treatment
- Herbal products that may decrease PSA levels within 4 weeks prior to Day 1 of treatment
- Systemic steroids \> 10 mg of prednisone/prednisolone per day within 4 weeks prior to Day 1 of treatment
- Major surgery within 4 weeks prior to Day 1 of treatment
- Planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery
- Structurally unstable bone lesions concerning for impending fracture
- Clinically significant cardiovascular disease including:
- MI/stroke within 6 months prior to day 1 of treatment
- Unstable angina within 3 months
- CHF with NYHA Class 3 or 4
- History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
- Uncontrolled hypertension (systolic BP \> 170 mmHg or diastolic BP \> 105 mmHg at screening) despite two concomitant antihypertensive therapies
- QTcF \> 500 msec on the screening ECG
- Active or symptomatic viral hepatitis or chronic liver disease
- History of unresolved adrenal dysfunction
- GI disorder that negatively affects absorption
- Required treatment with one of the prohibited concomitant medications
- Achlorhydria, either documented or suspected on the basis of an associated disease (e.g., pernicious anemia, atrophic gastritis, or certain gastric surgical procedures)
- History of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within 12 months prior to Day 1 of treatment, cerebral vascular accident or brain arteriovenous malformation
- Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ bladder cancer, or other cancer for which the patient has been disease-free for at least two years
- Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant psychiatric or neurological disorder, active or uncontrolled infection)
- Patient unwilling or unable to comply with this study protocol
Exclusion
Key Trial Info
Start Date :
November 15 2017
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
February 3 2021
Estimated Enrollment :
175 Patients enrolled
Trial Details
Trial ID
NCT03480646
Start Date
November 15 2017
End Date
February 3 2021
Last Update
October 29 2025
Active Locations (41)
Enter a location and click search to find clinical trials sorted by distance.
1
Alaska Urological Institute
Anchorage, Alaska, United States, 99503
2
Beverly Hills Cancer Center (BHCC)
Beverly Hills, California, United States, 90211
3
John Wayne Cancer Inst.
Duarte, California, United States, 91010
4
UCLA
Los Angeles, California, United States, 90095