MDACC Study Summary 2007-0583

Study Summary
No. 2007-0583:.......Prostate......Christopher Logothetis......Genitourinary Medical Oncology

Study Summary Title



Study Summary Number:	2007-0583

Study Title:	A Phase I/II Open Label Dose Escalation Study of the 17á Hydroxylase/C17, 20-Lyase Inhibitor, Abiraterone Acetate in Hormone Refractory Prostate Cancer.(COU-AA-002)

Physician

New Patient Referral



Name:	Christopher Logothetis	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Genitourinary Medical Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-2830 Contact us about clinical trials

General Information



Disease Group:	Prostate	Supported By:	Department of Defense Ortho Biotech, Oncology Research & Development, a Unit of Cougar Biotechnology, Inc.

Phase of Study:	Phase I/Phase II	Return Visit:	Patient must return weekly for the first Cycle and every 4 weeks in subsequent cycles (Phase I). Patients participating in the Phase II will return 7 days after starting medication and then at the beginning of each cycle (every 4 weeks).

Treatment Agents:	Abiraterone Acetate (CB7630)	Home Care:	Patients are responsible for taking oral medication daily.

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	N/A


Description/ Intervention:	The goal of this clinical research study is to learn if CB7630 (abiraterone acetate) can help to control prostate cancer. The safety of the combination of abiraterone acetate and prednisone will also be studied.

Study Objectives / Outcomes

Primary Objective:

PHASE I: To determine the maximum tolerated dose (MTD) of CB7630 administered orally on a continuous once-daily schedule in patients with HRPC.

PHASE II: To assess the proportion of patients achieving a > 50% PSA decline during therapy.

Secondary Objectives:
PHASE I:

To determine the need for supplementation with corticosteroids during therapy with CB7630.
To determine the effect of CB7630 on the pituitary-adrenal-gonad endocrine axis.
To evaluate the pharmacokinetic profile of abiraterone.
To assess the effect of food on the oral bioavailability of abiraterone tablets.
To collect preliminary data of anti-tumor activity during therapy with CB7630 according to: (i) PSA working group criteria and (ii) RECIST criteria in patients with measurable lesions.

PHASE II:

To assess the safety and tolerability of CB7630, with concurrent prednisone, in the study population
To assess PSA-based progression-free survival (PSA-PFS)
To assess the radiographic objective response rate (RAD-ORR) in patients with measurable lesions using RECIST
To assess radiographic progression-free survival (RAD-PFS)
To assess overall survival
To determine the duration of a PSA decline >50% and objective response (PSAORR),if applicable
To assess clinical benefit, as determined by disease stabilization and change in patient ECOG performance status.

Study Status Information



Study Activation / Registration Date:	02/25/2008

IRB Review and Approval Date:	10/09/2007

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Closed

Projected Accrual:	74

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Histologically confirmed adenocarcinoma of the prostate

2) No prior therapy with chemotherapy for prostate cancer

3) Ongoing gonadal androgen deprivation therapy with LHRH analogues or orchiectomy. Patients, who have not had an orchiectomy must be maintained on effective LHRH analogue therapy for the duration of the trial

4) Testosterone < 50 ng/dL

5) Progressive disease after androgen deprivation: PSA evidence for progressive prostate cancer consists of a PSA level of at least 5 ng/ml which has risen on at least 2 successive occasions, at least 2 weeks apart. If the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA will be required to document progression

6) The presence of objective metastatic disease is NOT required for study eligibility

7) Patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression (PD) following discontinuation of antiandrogen. PD after antiandrogen withdrawal is defined as 2 consecutive rising PSA values, obtained at least 2 weeks apart, or documented osseous or soft tissue progression. • Patients receiving flutamide, at least 1 of the PSA values must be obtained 4 weeks or more after stopping flutamide. • For patients receiving bicalutamide or nilutamide, at least one of the PSA values must be obtained 6 weeks or more after antiandrogen discontinuation

8) ECOG Performance Status 0-1

9) Age >18 years and able to comply with protocol requirements

10) Serum Creatinine </= 1.5 x ULN

11) K+ >/= 3.5 mM

12) Bilirubin </= 1.5xULN

13) AST and ALT </= 2.5 x ULN

14) Systolic blood pressure < 160 mmHg and diastolic blood pressure of < 110 mmHg documented on at least 3 different days (Documentation on three days not required for Phase II)

15) Baseline ACTH stimulation test demonstrating a peak cortisol >18 microg/dL

16) Life expectancy of >/= 12 weeks

17) Phase II Only - Neoadjuvant or adjuvant chemotherapy is only allowed if the last dose is > 1 year from Cycle 1 Day 1

18) Phase II Only - Target or Non-Target abnormalities must be present either on screening bone scan, CT or MRI

19) Phase II Only - No prior treatment with ketoconazole for the management of androgen independent prostate cancer

Exclusion Criteria:

1) Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES), or any systemic corticosteroid within 4 weeks prior to first dose of study drug

2) Initiation of bisphosphonate therapy within 4 weeks prior to first dose of study drug. Patients on stable doses of bisphosphonates that show subsequent tumor progression may continue on this medication; however, patients are not allowed to initiate bisphosphonate therapy during the study

3) Therapy with supplements or complementary medicines/botanicals within 4 weeks of first dose of study drug, except for any combination of the following: • conventional multivitamin supplements • selenium • lycopene • soy supplements

4) Prior radiation therapy completed < 4 weeks prior to enrollment

5) Prior chemotherapy for hormone refractory prostate cancer

6) Hemoglobin </= 9.0 g/dL

7) ANC </= 1.5 x 10^9/L

8) Platelets </= 100 x 10^9/L

9) Any currently active second malignancy, other than non-melanoma skin cancer. Patients are not considered to have a currently active malignancy, if they have completed therapy and are considered by their physician to be at least less than 30% risk of relapse over next 3 months.

10) Systolic blood pressure >/= 160 mmHg or diastolic blood pressure >/= 110 mmHg measured on at least 2 occasions.

11) Serum K+ < 3.5 mM

12) NYHA Class III or IV Congestive Heart Failure

13) Myocardial infarction within the 6 months prior to the first dose of study drug

14) Serious intercurrent infections or nonmalignant medical illnesses that are uncontrolled

15) Active psychiatric illnesses/social situations that would limit compliance with protocol requirements

16) Active or uncontrolled autoimmune disease that may require corticosteroid therapy during study

17) Phase II Only - Abnormal electrocardiogram, including any finding which would interfere with assessment of intervals (patients with long QT syndrome, bundle branch blocks or hemiblocks are prohibited)

Links

Registration Number: NCT00473746
Study Information on Clinical Trials Registry (clinicaltrials.gov)