A Study of Picoplatin and Docetaxel in Subjects With Prostate Cancer

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

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.

Study Overview

• Status: Unknown
• Conditions: Hormone Refractory Prostate Cancer
• Intervention / Treatment: Drug: Picoplatin; Drug: docetaxel

• Study Type: Interventional
• Enrollment (Anticipated): 95
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Chelyabinsk, Russian Federation, 454087
    • Chelyabinsk Regional Oncology Center
  • Moscow, Russian Federation, 105229
    • Burdenko Central Military Clinical Hospital
  • Moscow, Russian Federation, 117997
    • Russian Research Center of Radiology
  • Moscow, Russian Federation
    • Research Institute of Urology - Ministry of Health
  • St. Petersburg, Russian Federation, 188663
    • Leningrad Regional Oncology Center
  • St. Petersburg, Russian Federation, 194291
    • Central Medical Unit #122
  • St. Petersburg, Russian Federation, 194354
    • Therapeutic and Research Medical Center
  • St. Petersburg, Russian Federation, 196247
    • St. Petersburg City Hospital #26
  • St. Petersburg, Russian Federation, 198255
    • St. Petersburg City Oncology Center
  • Yaroslavl, Russian Federation, 150054
    • State Medical Institution of Yaroslavl Region / Regional Clinical Oncology Hospital
  • Kaluga Region
    • Obninsk, Kaluga Region, Russian Federation, 249036
      • Medical Radiology Research Center under the Russian Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 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.	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.
Active Comparator: 2; Docetaxel	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
In Part 1, the Maximum Tolerated Dose (MTD) will be determined	MTD
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

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	progression

Collaborators and Investigators

• Sponsor: Poniard Pharmaceuticals
• Investigators: Study Director: Robert Earhart, MD, Poniard Pharmaceuticals

Publications and helpful links

General Publications

• 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. doi: 10.1038/sj.bjc.6600854.
• 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.
• 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. doi: 10.1038/bjc.1998.59.
• 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. doi: 10.1016/s0959-8049(02)00107-7.
• 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. doi: 10.1016/s0959-8049(02)80020-x.
• 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. doi: 10.1093/annonc/mdh278.
• 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. doi: 10.1016/0959-8049(93)90040-m.

Helpful Links

• Poniard Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Anticipated): December 1, 2009
• Study Completion (Anticipated): July 1, 2010

Study Registration Dates

• First Submitted: March 15, 2007
• First Submitted That Met QC Criteria: March 15, 2007
• First Posted (Estimate): March 19, 2007

Study Record Updates

• Last Update Posted (Estimate): January 21, 2009
• Last Update Submitted That Met QC Criteria: January 20, 2009
• Last Verified: January 1, 2009

More Information

Terms related to this study

• Keywords: chemotherapy; prostate cancer; metastatic; docetaxel; picoplatin; hormone-refractory; platinum drug
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: 0502