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Metastatic Castration Resistant Prostate Cancer (mCRPC)Phase 1/2NCT03480646

ProSTAR: A Study Evaluating CPI-1205 in Patients With Metastatic Castration Resistant Prostate Cancer

A Phase 1/2 study testing CPI-1205, Cobicistat and Enzalutamide in people with Metastatic Castration Resistant Prostate Cancer (mCRPC), run by Constellation Pharmaceuticals at 41 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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-Resistant Prostate Cancer. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
CPI-1205, Cobicistat and Enzalutamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
175 participants
Where
41 sitesUnited States
Study dates
15 Nov 2017to 3 Feb 2021
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 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 49Show fewer
  • 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
  • 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

Who cannot join

  • 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
Show all 121Show fewer
  • 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)
  • 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

Trial locations and contacts

41 sites in 1 country.

41 sites in 1 country

United States41 sites

  • New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • Alaska Urological Institute

    Anchorage, Alaska, 99503

  • Rocky Mountain Cancer Centers

    Aurora, Colorado, 80045

  • University of Colorado Hospital - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • Texas Oncology - Central Austin Cancer Center

    Austin, Texas, 78731

  • University of Maryland

    Baltimore, Maryland, 21201

  • John Hopkins Kimmel Cancer Center

    Baltimore, Maryland, 21205

  • St. Luke's University

    Bethlehem, Pennsylvania, 18015

  • Beverly Hills Cancer Center (BHCC)

    Beverly Hills, California, 90211

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14263

  • University of North Carolina-Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Illinois Hospital and Health Systems

    Chicago, Illinois, 60612

  • Ohio State University - James Cancer Hospital and Solove Research Institute

    Columbus, Ohio, 43210

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • John Wayne Cancer Inst.

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 22710

  • North Shore Hematology Oncology Associates

    East Setauket, New York, 11733

  • Williamette Valley Cancer Institute and Research Center

    Eugene, Oregon, 97401

  • Texas Oncology- Fort Worth

    Fort Worth, Texas, 76104

  • Gettysburg Cancer Center

    Gettysburg, Pennsylvania, 17331

  • Greenville Hospital System, Institute for Translational Oncology Research

    Greenville, South Carolina, 29605

  • Virginia Oncology Associates

    Hampton, Virginia, 23666

  • Indiana University- Simon Cancer Center

    Indianapolis, Indiana, 46202

  • University of Florida

    Jacksonville, Florida, 32209

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89135

  • UCLA

    Los Angeles, California, 90095

  • Mount Sinai Comprehensive Cancer Center

    Miami, Florida, 33140

  • Carolina Urologic Research Center

    Myrtle Beach, South Carolina, 29572

  • Tulane University Health Sciences Center

    New Orleans, Louisiana, 70112

  • NYU Langone Medical Center Laura and Isaac Permlutter Cancer Center

    New York, New York, 10016

  • Icahn School of Medicine at Mt. Sinai

    New York, New York, 10029

  • GU Research Network

    Omaha, Nebraska, 68130

  • Maryland Oncology Hematology

    Rockville, Maryland, 20850

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612

  • Eastchester Center for Cancer Care

    The Bronx, New York, 10469

  • Toledo Clinic Cancer Center

    Toledo, Ohio, 43623

  • Compass Oncology - East

    Tualatin, Oregon, 97062

  • Texas Oncology- Tyler

    Tyler, Texas, 75702

Other trials in United States

About this study

Official title: A Phase 1b/2 Study of CPI-1205, a Small Molecule Inhibitor of EZH2, Combined With Enzalutamide or Abiraterone/Prednisone in Patients With Metastatic Castration Resistant Prostate Cancer

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-Resistant Prostate Cancer. The study was designed to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D) based on the safety, tolerability, pharmacokinetic, and efficacy profiles of CPI-1205 in combination with either enzalutamide or abiraterone/prednisone.

Following the determination of the MTD and RP2D, the study proceeded to Phase 2. Patients in Phase 2 received CPI-1205 at the RP2D in combination with either enzalutamide or abiraterone/prednisone versus either enzalutamide or abiraterone/prednisone as a control arm.

Read the 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 study initially had two phases: a Phase 1 dose-finding, dose-escalation study intended to establish the Recommended Phase 2 Dose (RP2D) of CPI-1205 for the Phase 2 portion.

The study underwent three amendments.

PHASE 1b In the Phase 1b dose-escalation phase and prior to Amendment 2, subjects were enrolled into Phase 1b dose level CPI-1205 PO three times daily (TID) + enzalutamide or abiraterone/prednisone.

In Amendment 2, new subjects were enrolled into cohorts including:

Dose-escalating CPI-1205 PO twice daily (BID) + fixed-dose cobicistat PO BID + enzalutamide Dose-escalating CPI-1205 PO BID + fixed-dose cobicistat PO BID + abiraterone/prednisone In Amendment 3, Phase 1b expansion cohort(s) were added in the heavily pretreated population (HPEC). An HPEC began enrollment if 0 out of 3 or 1 out of 6 subjects treated with a specific regimen (i.e., CPI-1205 with or without cobicistat, in combination with enzalutamide or abiraterone) at a given dose level during Phase 1b dose escalation experienced a dose-limiting toxicity (DLT).

Following determination of the maximum tolerated dose (MTD) in each of the CPI-1205 BID + cobicistat combinations (and possibly in the CPI-1205 TID combination) and after evaluation of the BID cohorts without cobicistat (if applicable), only one of the CPI-1205 dosing schedules was selected as the RP2D for each combination. One or both combinations proceeded to Phase 2 after consideration of pharmacokinetic (PK) and pharmacodynamic (PD) results, data from the HPEC(s), and safety data.

PHASE 2 If only one partner product was chosen for Phase 2, the study proceeded as an open-label randomized Phase 2 trial, with subjects randomized to either the combination arm (CPI-1205 at the RP2D [with or without cobicistat] in combination with enzalutamide or abiraterone/prednisone) or the control arm (enzalutamide or abiraterone/prednisone as monotherapy). If both partner products were chosen, the second Phase 2 was either a second open-label randomized trial or a single-arm Phase 2 trial (following a Simon's 2-stage design). The design of the second trial was determined by the Sponsor based on preliminary efficacy and PK.

CPI-1205 was administered orally TID or BID (as of Amendment 2). Cobicistat dosing began with one dose the evening prior to Day 1 of CPI-1205 and continued PO BID starting on Day 1. Enzalutamide and abiraterone were given PO once daily, and prednisone was given PO BID (or at the investigator's discretion).

Successive 28-day treatment cycles were repeated without planned breaks, as long as the combination was well tolerated, until radiographic disease progression, unequivocal clinical progression, or planned initiation of another systemic treatment. Investigators could continue treatment in subjects with progression in one site if other lesions might benefit. Subjects in the control arm who progressed had the option to cross over to the combination arm, provided they met eligibility criteria.

Being tested
CPI-1205, Cobicistat, Enzalutamide, Abiraterone, Prednisone
Keywords
Phase 1/2, Oncology, EZH2 Inhibitor
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CPI-1205Drug

    CPI-1205: Either 400 mg BID or 800 mg TID during Phase 1 dose-escalation and RP2D, 800 mg TID, for Phase 2

  • CobicistatDrug

    Cobicistat 150 mg PO BID

  • EnzalutamideDrug

    Enzalutamide 160mg PO QD

  • AbirateroneDrug

    Abiraterone 1000mg PO QD

  • PrednisoneDrug

    Prednisone 5mg PO BID

Study groups in NCT03480646
Study groupRoleWhat they receive
Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi + EnzaExperimentalCPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Enzalutamide 160 mg PO QD (28-day cycles)
Receives: Drug: CPI-1205; Drug: Cobicistat; Drug: Enzalutamide
Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi+ Abi/PredExperimentalCPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle)
Receives: Drug: CPI-1205; Drug: Cobicistat; Drug: Abiraterone; Drug: Prednisone
Phase 1b Dose Escalation: CPI-1205 800 mg TID + EnzaExperimentalCPI-1205 800 mg TID in combination with Enzalutamide 160 mg PO QD (28-day cycle)
Receives: Drug: CPI-1205; Drug: Enzalutamide
Phase 1b Dose Escalation: CPI-1205 800 mg TID + Abi/PredExperimentalCPI-1205 800 mg TID in combination with Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle)
Receives: Drug: CPI-1205; Drug: Abiraterone; Drug: Prednisone
Phase 1b HPEC: CPI-1205 800 mg TID + EnzaExperimentalCPI-1205 800 mg TID highly pretreated expansion cohort (HEPC) in combination with Enzalutamide 160 mg PO QD (28-day cycles)
Receives: Drug: CPI-1205; Drug: Enzalutamide
Phase 2 Randomized Controlled Group: EnzaActive comparatorDrug: Enzalutamide 160mg PO QD (28-day cycles)
Receives: Drug: Enzalutamide
Phase 2 Randomized at RP2D: CPI-1205 800 mg TID + EnzaExperimentalCPI-1205 (at Recommended Phase 2 Dose [RP2D]) in combination with Drug: Enzalutamide 160 mg PO QD
Receives: Drug: CPI-1205; Drug: Enzalutamide
Phase 2 Single Arm at RP2D: CPI-1205 800 mg TID + Abi/PredExperimentalCPI-1205 at 800 mg TID (Recommended Phase 2 Dose [RP2D]) 800 mg TID in combination with Abiraterone 1000 mg PO QD and Prednisone 5 mg PO BID (28-day cycles)
Receives: Drug: CPI-1205; Drug: Abiraterone; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy: Best Objective Response Rate Percent by Treatment Group

    Best overall response rate (%) defined as complete response (CR) + partial response (PR) divided by the total number of subjects as assessed by Investigator. The response assessment was performed per Prostate Cancer Working Group 3 (PCWG3) based on modifications of the RECIST 1.1 criteria. Per RECIST 1.1, a CR was assessed when all target lesions disappeared (any pathological lymph node must have reduction in short axis to <10 mm) in the post-baseline scan. A PR was assessed when there was at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: Up to 2 years [or until disease progression or unacceptable toxicity]

  2. Efficacy: Percentage (%) of Subjects With PSA30

    The number of subjects who had a confirmed reduction of 30% of prostate-specific antigen (PSA30) from baseline

    Measured: 2 years [or until progressive disease or unacceptable toxicity]

  3. Efficacy: Percentage (%) of Subjects With PSA50

    The number of subjects who had a confirmed reduction of 50% of prostate-specific antigen (PSA50) from baseline

    Measured: 2 years [or until progressive disease or unacceptable toxicity]

  4. Efficacy: Composite Response Rate (%) for Phase 2 Randomized and Phase 2 Single-arm Treatment Groups

    Subjects who had a circulating tumor cell of 30% (CTC 30%) or an objective response rate divided by the number of evaluable subjects

    Measured: Up to 2 years [or until progressive disease or unacceptable toxicity]

Secondary outcomes (2)

  1. Efficacy: Best Responses by Treatment Group

    Best overall response defined as complete response (CR), partial response (PR); stable disease (SD); progressive disease (PD); and unknown/missing for the Phase 1b dose-escalation group, the Phase 1b HPEC group, the Phase 2 randomized groups, crossover group and the Phase 2 single-arm group. Assessed by Investigator

    Measured: Up to 2 years [or until disease progression or unacceptable toxicity]

  2. Safety: Number of Participants With Treatment-emergent AEs Leading to Treatment Discontinuation

    Treatment-emergent Adverse events (AEs) leading to subjects withdrawing from treatment

    Measured: Up to 2 years [or until clinical progression, radiographic disease progression, or until unacceptable toxicity]

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Mar 2018
  2. Study start15 Nov 2017
  3. Primary completion3 Feb 2021
  4. Study completion3 Feb 2021

Resources

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
175 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03480646
Sponsor's protocol ID
1205-201
Status last verified
Oct 2025
First submitted
7 Mar 2018
Last updated
29 Oct 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CPI-1205, Cobicistat and Enzalutamide in people with Metastatic Castration Resistant Prostate Cancer (mCRPC), run by Constellation Pharmaceuticals at 41 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 49 inclusion and 121 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 29 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 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 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 29 Oct 2025). 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?

Efficacy: Best Objective Response Rate Percent by Treatment Group (time frame: Up to 2 years [or until disease progression or unacceptable toxicity]). The study lists 4 primary outcomes in all. 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 NCT03480646.

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 29 Oct 2025.

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