Docetaxel, Prednisone, and Pasireotide in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01468532
• Date of registration: 25/10/2011
• Primary sponsor: Barbara Ann Karmanos Cancer Institute
• Public title: Docetaxel, Prednisone, and Pasireotide in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer
• Scientific title: Phase I/II Trial to Establish the Safety and Preliminary Efficacy of the Combination of Docetaxel, Prednisone, and SOM 230 (Pasireotide) in Metastatic Castrate Resistant Prostate Cancer (CRPC).
• Date of first enrolment: October 2011
• Target sample size: 24
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01468532
• Study type: Interventional
• Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Ulka N. Vaishampayan

• Name: Ulka Vaishampayan
• Affiliation: Barbara Ann Karmanos Cancer Institute

Key inclusion & exclusion criteria

Inclusion Criteria:

- Histologically confirmed prostate adenocarcinoma with metastasis, and objective
progression or rising PSA despite androgen deprivation therapy and antiandrogen
withdrawal when applicable; patients with rising PSA must demonstrate a rising trend
with 2 successive elevations at a minimum interval of 1 week; a minimum PSA of 5
ng/ml or new areas of bony metastases on bone scan are required for patients with no
measurable disease; no minimum PSA requirement for patients with measurable disease

- Patient must not have received any prior chemotherapy for metastatic disease; all
patients must be documented to be castrate with a testosterone level < 0.5 ng/ml;
luteinizing hormone-releasing hormone (LHRH) agonist therapy must be continued, if
required to maintain castrate levels of testosterone; patients must be off
antiandrogens for a minimum of 4 weeks for flutamide and 6 weeks for bicalutamide or
nilutamide

- Minimum of four weeks since any major surgery, completion of radiation, or completion
of all prior systemic anticancer therapy (adequately recovered from the acute
toxicities of any prior therapy)

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Life expectancy 12 weeks or more

- Absolute neutrophil (ANC) >= 1.5 x 10^9/L

- Platelets >= 100 x 10^9/L

- Hemoglobin (Hgb) > 9 g/dL

- Serum bilirubin =< 2 x upper limit of normal (ULN)

- Serum transaminases activity =< 3 x ULN, with the exception of serum transaminases (<
5 x ULN) if the patient has liver metastases

- Serum creatinine =< 1.5 x ULN

- Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND fasting triglycerides =<
2.5 x ULN; NOTE: in case one or both of these thresholds are exceeded, the patient
can only be included after initiation of appropriate lipid lowering medication

- Patients must be advised of the importance of using effective birth control measures
during the course of the study

- Signed informed consent to participate in the study must be obtained from patients
after they have been fully informed of the nature and potential risks by the
investigator (or his/her designee) with the aid of written information

Exclusion Criteria:

- Prior treatment with any cytotoxic chemotherapy, radiation, immunotherapy, or any
investigational drug within the preceding 4 weeks

- Patients who have undergone major surgery within 4 weeks prior to study enrollment

- Chronic treatment with immunosuppressive agents except steroids

- Patients should not receive immunization with attenuated live vaccines during study
period or within 1 week of study entry

- Uncontrolled brain or leptomeningeal metastases, including patients who continue to
require glucocorticoids for brain or leptomeningeal metastases

- Patients with prior or concurrent malignancy except for the following: adequately
treated basal cell or squamous cell skin cancer, or other adequately treated in situ
cancer, or any other cancer from which the patient has been disease free for five
years

- Patients with uncontrolled diabetes mellitus, which is defined as a hemoglobin A1C >
8% on therapy or > 7% without therapy, or a fasting plasma glucose > 1.5 ULN; Note:
at the principle investigator's discretion, non-eligible patients can be re-screened
after adequate medical therapy has been instituted

- Patients with symptomatic cholelithiasis

- Patients who have congestive heart failure (New York Heart Association [NYHA] Class
III or IV), unstable angina, sustained ventricular tachycardia, ventricular
fibrillation, clinically significant bradycardia, advanced heart block or a history
of acute myocardial infarction within the six months preceding enrollment

- QT-related exclusion criteria:

- Patients with baseline QTc > 450 msec

- History of syncope or family history of idiopathic sudden death

- Sustained or clinically significant cardiac arrhythmias

- Patients with risk factors for Torsades de Pointes such as hypokalemia,
hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or
high-grade AV block

- Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by
diabetes or Parkinson's disease), human immunodeficiency virus (HIV), cirrhosis,
uncontrolled hypothyroidism or cardiac failure

- Concomitant medication(s) known to prolong the QT interval

- Patients with the presence of active or suspected acute or chronic uncontrolled
infection or with a history of immunocompromise, including a positive HIV test result
(enzyme-linked immunosorbent assay [ELISA] and Western blot)

- Patients who have any severe and/or uncontrolled medical conditions or other
conditions that could affect their participation in the study such as:

- Severely impaired lung function

- Any active (acute or chronic) or uncontrolled infection/ disorders

- Nonmalignant medical illnesses that are uncontrolled or whose control may be
jeopardized by the treatment with the study therapy

- Known hypersensitivity to somatostatin analogues or any component of the pasireotide
or octreotide long-acting release (LAR) formulations

- History of noncompliance to medical regimens

- Patients unwilling to or unable to comply with the protocol

- Men and any female partners of child-bearing potential must agree to use adequate
contraception (hormonal or barrier method of birth control) prior to study entry and
for the duration of study participation and for additional 2 months after finishing
therapy; should a patient's sexual partner become pregnant or suspect she is pregnant
while patient is participating in this study, he should inform the treating physician
immediately



Age minimum: 18 Years
Age maximum: N/A
Gender: Male

Health Condition(s) or Problem(s) studied

Adenocarcinoma of the Prostate

Hormone-resistant Prostate Cancer

Recurrent Prostate Cancer

Stage IV Prostate Cancer

Intervention(s)

Drug: docetaxel

Drug: pasireotide

Drug: prednisone

Primary Outcome(s)

Occurrence of adverse events and the associated grade per NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 to identify the maximum tolerated dose (MTD) of pasireotide in combination with docetaxel and prednisone [Time Frame: Up to day 57]

Secondary Outcome(s)

All specific types of toxicity as assessed via NCI CTCAE version 4.0 [Time Frame: On days 1, 8, 15, 22, 29, 36 43, 50 and 57]

Measurement of levels of IGF-1, serum chromogranin A (SCA), and neuron specific enolase (NSE), pre-therapy, post-therapy, and the change between time points and association with duration of TTP and OS [Time Frame: Baseline and days 22 and 43]

Measurements of CTC counts pre-therapy, post-therapy, and the change between time-points and association with duration of TTP and OS [Time Frame: Baseline and days 22 and 43]

Measurements of tumor using Response Evaluation Criteria In Solid Tumors (RECIST) criteria before and after treatment with the combination of pasireotide in combination with docetaxel [Time Frame: Every 12 weeks for the first 36 weeks and then every 16 weeks thereafter]

Overall Survival (OS) [Time Frame: Every 3 months for the first 9 months on study then every 4 months after the first 9 months on study]

Percentage prostate-specific antigen (PSA) decline noted [Time Frame: On days 1, 8, 15, 22, 29, 36 43, 50 and 57]

Pharmacokinetics (PK) parameters [Time Frame: Predosing/end of infusion/2, 3, 4 ,7, 24 and 48 hours after start of docetaxel; Day 43; predosing for docetaxel and pasireotide/end of infusion/2, 3, 4, 7, 24 hours day 44/48 hours day 45 after start of infusion; days 29, 57, and 85 prior to pasireotide]

Time to Progression (TTP) [Time Frame: Every 3 months for the first 9 months on study then every 4 months after the first 9 months on study]

Secondary ID(s)

2011-031

NCI-2011-03216

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)