A Study of Picoplatin and Docetaxel in Subjects With Prostate Cancer

Hormone Refractory Prostate Cancer Clinical Trial

Official title:

A Phase 1/2 Study of Picoplatin and Docetaxel (With Prednisone) in Subjects With Chemotherapy-Naive Metastatic Hormone-Refractory Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00448734
• Other study ID #: 0502
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: March 15, 2007
• Last updated: January 20, 2009
• Start date: June 2006
• Est. completion date: July 2010

Study information

• Verified date: January 2009
• Source: Poniard Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will review the safety of picoplatin, a new type of platinum drug, with docetaxel, a drug commonly used in the treatment of prostate cancer. Patients who are eligible for this study will have had a diagnosis of hormone-refractory prostate cancer that has metastasized to other areas of the body, and have not been previously treated with chemotherapy drugs. Picoplatin will be administered in combination with docetaxel and prednisone to identify the maximum tolerated dose (MTD). Patients will receive IV treatments of picoplatin with docetaxel every 3 weeks, with prednisone, 5 mg orally, twice daily.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 95
• Est. completion date: July 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate.

• Radiologic evidence of metastatic disease (Jewett-Whitmore Stages D1-D2 or TNM Stage N1-3 or M1).

• Disease progression or recurrence documented by either: increasing serum PSA on three consecutive measurements each obtained at least one week apart, or findings on radiographic imaging studies.

• Non-surgically castrate subjects must be receiving androgen ablation therapy as maintenance therapy.

• Adequate hormonal therapy as documented by a castrate level of serum testosterone (all subjects without surgical castration must have a serum testosterone less than 50 ng/ml).

• At least 4 weeks must have elapsed after the withdrawal of antiandrogens (6 weeks in the case of bicalutamide).

• Age 18 years and over. Subjects older than 80 years should be entered on study only if considered "physiologically appropriate" for combination chemotherapy.

• ECOG performance score (PS) of 0 or 1.

• Stable levels of pain for at least 7 days before study entry.

• Life expectancy more than 3 months.

• At least 28 days must have elapsed since prior radiotherapy.

• At least 28 days must have elapsed since any prior investigational agent.

• Absolute neutrophil count (ANC) at least 1.5 x 10^9th/L.

• Platelet count at least 100 x 10^9th/L.

• Hemoglobin at least 10 g/dL.

• Serum AST and ALT levels = 1.5 times upper limit of normal (ULN).

• Serum bilirubin = ULN.

• Serum creatinine = ULN.

• All subjects must agree to use appropriate birth control methods while on study and until 1 month after completion of study chemotherapy.

Exclusion Criteria:

• Prior treatment with cytotoxic agents (except estramustine), radioisotopes, or biological therapies other than hormones.

• Clinical evidence of brain or leptomeningeal metastases.

• Symptomatic peripheral neuropathy of Grade 2 or higher.

• History of another cancer within the preceding 5 years, except for superficial skin cancers.

• Known hypersensitivity to drugs formulated with Polysorbate 80.

• Prior radiotherapy that included = 30% of the bone marrow (e.g., the whole of the pelvis or half of the spine).

• Uncontrolled intercurrent illness (e.g., active infection).

• Serious medical or psychiatric illness that could potentially interfere with the completion of the study treatment according to this protocol.

• History of serious cardiac disease, defined as myocardial infarction within six months of enrollment, congestive heart failure classified by the New York Heart Association as Class III or IV, uncontrolled cardiac arrhythmias, poorly controlled or unstable angina, or electrocardiographic evidence of acute ischemia.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hormone Refractory Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Picoplatin
The treatment regimen will be the assigned dose of picoplatin plus docetaxel, 60 mg/m2 or 75 mg/m2, once every three weeks, plus prednisone (or prednisolone, if prednisone is not available), 5 mg orally twice daily beginning on day 1 and continuing daily until therapy is discontinued. Docetaxel will be given intravenously over 60 minutes, followed 30 minutes later by picoplatin as a 1-2 hour intravenous infusion.
• docetaxel
The treatment regimen will be the assigned dose of picoplatin plus docetaxel, 60 mg/m2 or 75 mg/m2, once every three weeks, plus prednisone (or prednisolone, if prednisone is not available), 5 mg orally twice daily beginning on day 1 and continuing daily until therapy is discontinued. Docetaxel will be given intravenously over 60 minutes, followed 30 minutes later by picoplatin as a 1-2 hour intravenous infusion.

Locations

Country	Name	City	State
Russian Federation	Chelyabinsk Regional Oncology Center	Chelyabinsk
Russian Federation	Burdenko Central Military Clinical Hospital	Moscow
Russian Federation	Research Institute of Urology - Ministry of Health	Moscow
Russian Federation	Russian Research Center of Radiology	Moscow
Russian Federation	Medical Radiology Research Center under the Russian Academy of Medical Sciences	Obninsk	Kaluga Region
Russian Federation	Central Medical Unit #122	St. Petersburg
Russian Federation	Leningrad Regional Oncology Center	St. Petersburg
Russian Federation	St. Petersburg City Hospital #26	St. Petersburg
Russian Federation	St. Petersburg City Oncology Center	St. Petersburg
Russian Federation	Therapeutic and Research Medical Center	St. Petersburg
Russian Federation	State Medical Institution of Yaroslavl Region / Regional Clinical Oncology Hospital	Yaroslavl

Sponsors (1)

Lead Sponsor	Collaborator
Poniard Pharmaceuticals

Country where clinical trial is conducted

Russian Federation, 

References & Publications (7)

Beale P, Judson I, O'Donnell A, Trigo J, Rees C, Raynaud F, Turner A, Simmons L, Etterley L. A Phase I clinical and pharmacological study of cis-diamminedichloro(2-methylpyridine) platinum II (AMD473). Br J Cancer. 2003 Apr 7;88(7):1128-34. — View Citation

Canobbio L, Guarneri D, Miglietta L, Decensi A, Oneto F, Boccardo F. Carboplatin in advanced hormone refractory prostatic cancer patients. Eur J Cancer. 1993;29A(15):2094-6. — View Citation

Douillard JY, Schiller J. ZD0473 combined with other chemotherapeutic agents for the treatment of solid malignancies. Eur J Cancer. 2002 Dec;38 Suppl 8:S25-31. — View Citation

Gelmon KA, Stewart D, Chi KN, Chia S, Cripps C, Huan S, Janke S, Ayers D, Fry D, Shabbits JA, Walsh W, McIntosh L, Seymour LK. A phase I study of AMD473 and docetaxel given once every 3 weeks in patients with advanced refractory cancer: a National Cancer Institute of Canada-Clinical Trials Group trial, IND 131. Ann Oncol. 2004 Jul;15(7):1115-22. — View Citation

Holford J, Raynaud F, Murrer BA, Grimaldi K, Hartley JA, Abrams M, Kelland LR. Chemical, biochemical and pharmacological activity of the novel sterically hindered platinum co-ordination complex, cis-[amminedichloro(2-methylpyridine)] platinum(II) (AMD473). Anticancer Drug Des. 1998 Jan;13(1):1-18. — View Citation

Holford J, Sharp SY, Murrer BA, Abrams M, Kelland LR. In vitro circumvention of cisplatin resistance by the novel sterically hindered platinum complex AMD473. Br J Cancer. 1998;77(3):366-73. — View Citation

Rogers P, Boxall FE, Allott CP, Stephens TC, Kelland LR. Sequence-dependent synergism between the new generation platinum agent ZD0473 and paclitaxel in cisplatin-sensitive and -resistant human ovarian carcinoma cell lines. Eur J Cancer. 2002 Aug;38(12):1653-60. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	In Part 1, the Maximum Tolerated Dose (MTD) will be determined		MTD	Yes
Primary	In Part 2, PSA response will be measured (reduction of at least 50% of PSA from baseline, with reduction maintained for at least 4 weeks)		response	No
Secondary	Progression free survival		progression	No