Study of Picoplatin Efficacy After Relapse (SPEAR)

• ClinicalTrials.gov Identifier: NCT00465491
• Recruitment Status: Unknown
• First Posted: April 25, 2007
• Last Update Posted: April 14, 2009
• Sponsor: Poniard Pharmaceuticals
• Information provided by: Poniard Pharmaceuticals

Tracking Information

• First Submitted Date: April 23, 2007
• First Posted Date: April 25, 2007
• Last Update Posted Date: April 14, 2009
• Study Start Date: April 2007
• Estimated Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 20, 2009): overall survival [ Time Frame: death ]
• Original Primary Outcome Measures (submitted: April 23, 2007): overall survival

Current Secondary Outcome Measures (submitted: January 20, 2009)

• objective response rate [ Time Frame: progression ]
• disease control rate [ Time Frame: progression ]
• duration of response [ Time Frame: progression ]
• progression-free survival [ Time Frame: death ]

Original Secondary Outcome Measures (submitted: April 23, 2007)

• objective response rate
• disease control rate
• duration of response
• progression-free survival

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Picoplatin Efficacy After Relapse
• Official Title: A Randomized, Controlled Phase III Trial of Picoplatin and BSC Versus BSC Alone in Patients With Small Cell Lung Cancer (SCLC), Refractory or Progressive Within Six Months of Completing First-Line, Platinum-Containing Chemotherapy.
• Brief Summary: Picoplatin is a new type of platinum drug that has been investigated in several clinical trials, and may provide an improved safety profile over current treatment options. This study is designed to compare the efficacy and safety of picoplatin plus Best Supportive Care (BSC) with BSC alone. Best Supportive Care includes care and treatment to optimize the comfort of patients and their ability to function, as well as to minimize the side-effects of anti-cancer treatments.
• Detailed Description: This Phase 3 study will enroll subjects with Small Cell Lung Cancer (SCLC) who are refractory or progressive within 6 months of completing first-line, platinum-containing chemotherapy. Subjects will be centrally randomized 2:1 to receive picoplatin plus BSC every 3 weeks, or BSC alone. After discontinuation of picoplatin, all subjects will continue to receive BSC and will continue to be evaluated every 3 weeks until discontinuation from the study, death, or the end of the study. After discontinuation of picoplatin, subjects may be treated with another chemotherapy at their physician's discretion and then will be followed for survival.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Small Cell Lung Cancer

Intervention

• Drug: picoplatin
  IV picoplatin 150mg/m2 q3wk
• Other: best supportive care
  best supportive care

Study Arms

• Experimental: 1
  Picoplatin
  Intervention: Drug: picoplatin
• 2
  BSC
  Intervention: Other: best supportive care

Publications *

• Raynaud FI, Boxall FE, Goddard PM, Valenti M, Jones M, Murrer BA, Abrams M, Kelland LR. cis-Amminedichloro(2-methylpyridine) platinum(II) (AMD473), a novel sterically hindered platinum complex: in vivo activity, toxicology, and pharmacokinetics in mice. Clin Cancer Res. 1997 Nov;3(11):2063-74.
• 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.
• Giaccone G, O'Brien ME, Byrne MJ, Bard M, Kaukel E, Smit B. Phase II trial of ZD0473 as second-line therapy in mesothelioma. Eur J Cancer. 2002 Dec;38 Suppl 8:S19-24.
• Treat J, Schiller J, Quoix E, Mauer A, Edelman M, Modiano M, Bonomi P, Ramlau R, Lemarie E. ZD0473 treatment in lung cancer: an overview of the clinical trial results. Eur J Cancer. 2002 Dec;38 Suppl 8:S13-8.
• Gore ME, Atkinson RJ, Thomas H, Cure H, Rischin D, Beale P, Bougnoux P, Dirix L, Smit WM. Results of ZD0473 in platinum-pretreated ovarian cancer: analysis according to platinum free interval. Eur J Cancer. 2002 Dec;38 Suppl 8:S7-12.
• 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.
• 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.
• Sharp SY, O'Neill CF, Rogers P, Boxall FE, Kelland LR. Retention of activity by the new generation platinum agent AMD0473 in four human tumour cell lines possessing acquired resistance to oxaliplatin. Eur J Cancer. 2002 Nov;38(17):2309-15.
• Kawamura-Akiyama Y, Kusaba H, Kanzawa F, Tamura T, Saijo N, Nishio K. Non-cross resistance of ZD0473 in acquired cisplatin-resistant lung cancer cell lines. Lung Cancer. 2002 Oct;38(1):43-50.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: April 23, 2007): 399
• Original Enrollment: Same as current
• Study Completion Date: Not Provided
• Estimated Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histological or cytological diagnosis of SCLC or combined SCLC/non-small cell lung cancer (NSCLC) defined as SCLC mixed with squamous cell carcinoma, adenocarcinoma, or large cell carcinoma.
• One and only 1 prior cisplatin or carboplatin-containing chemotherapy regimen for SCLC within the scope of the National Comprehensive Cancer Network (NCCN) Guidelines (Section 5.4.1).
• Radiological evidence of SCLC that never responded or progressed within 90 days after completion of first-line therapy (refractory); or responded initially to first-line therapy but progressed between 91 and 180 days after treatment was completed (progressed within 91 to 180 days).
• CT scans of head, chest and abdomen (including adrenal and full extent of liver) with contrast, preferably within 14 days prior to randomization (up to 21 days is allowed if necessary). MRI is acceptable in the case of allergy to contrast agents. The presence or absence of measurable disease gy RECIST must be documented from the baseline CT or MRI scan.
• Patients with brain metastases must have been treated with brain irradiation. Only patients wtih asymptomatic brain metastases are eligible for this study.
• ECOG PS 0, 1 or 2 within 3 days prior to randomization (Appendix II).
• Life expectancy of at least 8 weeks within 3 days prior to randomization.
• At least 21 days must have elapsed since the most recent prior chemotherapy dose, with evidence of hematological recovery.
• At least 14 days must have elapsed since the most recent prior radiotherapy dose.
• At least 14 days must have elapsed since prior surgery except for the placement of venous access device or bronchoscopy.
• Subject must be recovered to ≤ Grade 1 toxicity from all non-hematological adverse effects of prior therapies (excluding alopecia).
• Age 18 years or over.
• ANC ≥ 1.5 x 109/L.
• Platelet count ≥ 100 x 109/L.
• Hemoglobin of ≥ 90 g/L (transfusion permitted to achieve this hemoglobin).
• Aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels ≤ 2.5 times upper limit of normal (ULN) or ≤ 5 times ULN if liver involvement is present.
• Bilirubin of ≤ 1.5 times upper limit of normal (ULN).
• Blood urea nitrogen ≤ 1.5 times ULN (hypovolemic subjects may be hydrated to achieve this BUN).
• Creatinine clearance of ≥ 50 mL/min, as calculated by the Cockcroft-Gault formula (Appendix III).
• Women of childbearing potential must have a negative pregnancy test (serum or urine). Sexually active couples of child-bearing potential must agree to use appropriate birth control methods during chemotherapy and for 3 months after chemotherapy.
• Signed informed consent.

Exclusion Criteria:

• Prior radiotherapy that included ≥ 30% of the bone marrow (Appendix IV).
• Pleural effusion as the only radiological evidence of SCLC.
• Untreated or symptomatic brain or central nervous system (CNS) metastases.
• Grade 2 or higher peripheral neuropathy.
• Significant cardiac disease, defined as myocardial infarction within 3 months prior to randomization, congestive heart failure classified by the New York Heart Association as Class III or IV (Appendix V), uncontrolled cardiac arrhythmias, poorly controlled or unstable angina, or electrocardiographic evidence of acute ischemia.
• Serious medical or psychiatric illness that could potentially interfere with the completion of study treatment according to this protocol, e.g., active infection, Crohn's disease, ulcerative colitis, etc.
• Use of other investigational drugs within 30 days prior to randomization.
• Breast-feeding.
• History of any other malignancy within 5 years, with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Belarus, Bosnia and Herzegovina, Bulgaria, Chile, Croatia, Hungary, India, Latvia, Montenegro, Poland, Romania, Russian Federation, Serbia, Ukraine

Administrative Information

• NCT Number: NCT00465491
• Other Study ID Numbers: 0601
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Hazel Breitz, MD, Poniard Pharmaceuticals, Inc.
• Study Sponsor: Poniard Pharmaceuticals
• Collaborators: Not Provided

Investigators

• Study Director: Dr. Hazel Breitz, M.D.; Poniard Pharmaceuticals

• PRS Account: Poniard Pharmaceuticals
• Verification Date: April 2009