Clinical trial NCT01866423: Orteronel in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer
Official title: Phase 2 Trial of TAK-700 (Also Known as Orteronel) Without Prednisone for Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Adenocarcinoma of the Prostate
Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Millennium Pharmaceuticals, Inc.
First posted: 2013-05-31
Enrollment: 4
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial studies how well orteronel works in treating patients with metastatic hormone-resistant prostate cancer. Orteronel may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description: PRIMARY OBJECTIVES:

I. To assess the relationship between circulating tumor cell (CTC)-based androgen receptor (AR) expression level and \>=-50% prostate-specific antigen (PSA) decline following 12 weeks of therapy with TAK-700 (orteronel).

SECONDARY OBJECTIVES:

I. To assess changes in PSA and CTC levels and time to PSA progression (best response, decline at 12 weeks as continuous variable, etc.) with or without prior docetaxel-based treatment.

II. To assess measurable disease response and time to radiographic disease progression for castration-resistant prostate cancer (CRPC) with or without prior docetaxel-based treatment.

III. To explore relationships between endocrine and clinical responses.

IV. To confirm the safety of TAK-700 administered without prednisone in patients with metastatic CRPC.

OUTLINE: Patients receive orteronel orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed adenocarcinoma of the prostate
* Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
* Patients, even if surgically sterilized (i.e., status post vasectomy), who agree to practice effective barrier contraception during the entire study treatment period and for 4 months after the last dose of study drug, or
* Agree to completely abstain from intercourse
* Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be =\< 2.5 x the upper limit of normal (ULN)
* Total bilirubin =\< 1.5 x ULN
* Estimated creatinine clearance using the Cockcroft-Gault formula must be \> 40 mL/minute
* Absolute neutrophil count (ANC) \>= 1500 cells/microliter
* Platelet count \>= 100,000 cells/microliter
* Testosterone \< 50 ng/dL
* Screening calculated ejection fraction of \>= 50% by multiple gated acquisition (MUGA) scan or echocardiogram; metastatic progression on primary androgen-deprivation therapy (medical or surgical castration)
* Progression requiring a change in oncologic therapy defined by any of the following:

  * Radiographic progression: appearance or increase in measurable lesions on cross-sectional imaging or appearance of one or more new lesions on bone scan \* Rising PSA (\>= 2 ng/ml) which has risen on two occasions \>= 1 week apart
  * Clinical progression evidenced by increased pain or other cancer-related symptoms
* Patients should have recovered from prior oncologic therapies to a Common Terminology Criteria (CTC) grade =\< 1 except stable neuropathy or alopecia at National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade =\< 2; if rapid clinical progression is documented by imaging, changes in PSA, or symptoms, then study treatment can begin \>= 2 weeks from prior therapy; otherwise, the following time periods between prior anti-cancer therapies and study treatment day 1 will apply:

  * \>= 3 weeks for prior cytotoxic therapies
  * \>= 4 weeks for flutamide or nilutamide
  * \>= 6 weeks for bicalutamide
  * \>= 6 weeks since bone targeted radiopharmaceutical (e.g. samarium-153, radium-223)
* Gonadotropin-releasing hormone (GnRH) agonists (leuprolide acetate, goserelin, etc.) or antagonists (degarelix, etc.) should be continued in patients without surgically-induced castrate androgen levels
* For chemotherapy naïve castration-resistant prostate cancer who are moderately symptomatic or who have hepatic metastasis: subjects must not be a candidate for docetaxel-based chemotherapy.

Exclusion Criteria:

* History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of grade \> 2 (NCI CTCAE, version 4), thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (e.g. pericardial effusion, restrictive cardiomyopathy) within 6 months prior to first dose of study drug; chronic stable atrial fibrillation on stable anticoagulant therapy is allowed
* New York Heart Association class III or IV heart failure
* Electrocardiogram (ECG) abnormalities of:

  * Q-wave infarction, unless identified 6 or more months prior to screening
  * Corrected QT (QTc) interval \> 460 msec
* Patient has received other investigational drugs within 28 days before enrollment
* Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy
* Known hypersensitivity to compounds related to TAK-700 or to TAK-700 excipients
* Uncontrolled hypertension despite appropriate medical therapy (blood pressure \[BP\] of greater than 160 mmHg systolic and 90 mmHg diastolic at 2 separate measurements no more than 60 minutes apart during the screening visit); Note: patients may be rescreened after adjustment of antihypertensive medications
* Known active chronic hepatitis B or C, life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with participation in this study
* Likely inability to comply with the protocol or cooperate fully with the investigator and site personnel
* Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of TAK-700, including difficulty swallowing tablets
* Prior treatment with \>= 3 lines of cytotoxic chemotherapy for metastatic prostate cancer
* Prior treatment with TAK-700

Primary outcomes:
measure: Androgen Receptor (AR) Protein Expression Levels in CTCs
timeFrame: Up to 4 weeks
measure: PSA Response, Defined as Occurrence of PSA Decline to Greater Than or Equal to 50% From Baseline
timeFrame: At 12 weeks
Secondary outcomes:
measure: Best PSA Response
timeFrame: Up to 24 weeks
measure: Absolute Change in PSA
timeFrame: Baseline to 24 weeks
measure: Overall Response Rate Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and PCWG2 Criteria
timeFrame: Up to 3 years
measure: Duration of Response Using RECIST Version 1.1 and PCWG2 Criteria
timeFrame: Up to 3 years
measure: Number of Participants With Grade 3 or Higher Toxicity
timeFrame: 30 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
Study officials:
affiliation: University of Southern California
name: Mitchell Gross
role: PRINCIPAL_INVESTIGATOR
References: