Study of Picoplatin Efficacy After Relapse

Small Cell Lung Cancer Clinical Trial

— SPEAR  

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00465491
• Other study ID #: 0601
• Status: Active, not recruiting
• Phase: Phase 3
• First received: April 23, 2007
• Last updated: April 13, 2009
• Start date: April 2007

Study information

• Verified date: April 2009
• Source: Poniard Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationEuropean Union: European Medicines AgencyRussia: Pharmacological Committee, Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 399
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• picoplatin
IV picoplatin 150mg/m2 q3wk

Other:
• best supportive care
best supportive care

Locations

Country	Name	City	State
Argentina	Centro Oncologico	Buenos Aires
Argentina	CETEN Centro de Estudio y Tratamiento de Enfermedades Neoplasicas	Buenos Aires
Argentina	Clinica Constituyentes	Buenos Aires
Argentina	Consultorios Privados	Buenos Aires
Argentina	IADT (Insttituto Argentino de Diagnostico y Tratamiento S.A.)	Buenos Aires
Argentina	Instituto Alexander Fleming	Buenos Aires
Argentina	PALIAR	Buenos Aires
Argentina	IONC	Cordoba
Argentina	Centro Oncologico de Rosario	Santa Fe
Argentina	ISIS Clinica Especializada	Santa Fe
Argentina	Centro Medico San Roque	Tucuman
Belarus	Gomel Regional Oncological Dispensary	Gomel
Belarus	Institution of Healthcare "Grodno Regional Clinical Hospital	Grodno
Belarus	Minsk City Clinical Oncology Dispensary	Minsk
Belarus	Research Institute of Oncology and Medical Radiology named by N.N. Aleksandrov	Minsk
Belarus	Vitebsk Regional Oncology Dispensary	Vitebsk
Bosnia and Herzegovina	Clinic for Lung Diseases, Clinical Center, Banja Luka	Banja Luka
Bosnia and Herzegovina	Clinic of Pulmonary Diseases Podhrastovi	Sarajevo
Bulgaria	Multiprofile Hospital for Active Treatment, Dr. Tota Venkova	Gabrovo
Bulgaria	University Multifunctional Hospital for Active Treatment "Dr. Georgi Stranski"	Pleven
Bulgaria	District Dispensary for Cancer Diseases with Inpatient Hospital Plovdiv	Plovdiv
Bulgaria	Regional Oncodispensary with Inpatient Sector	Rousse
Bulgaria	Inter-district Dispensary for Cancer Diseases w/Inpatient Hospital	Shumen
Bulgaria	Regional Oncodispensary with Inpatient Sector-Sofia District	Sofia
Bulgaria	Inter-district Dispensary for Cancer Disease w/Inpatient Hospital "Dr. Marko Markov", Varna	Varna
Bulgaria	Multiprofile Hospital for Active Treatment "St. Marina"	Varna
Chile	Instituto Nacional de Cancer	Santiago
Croatia	Clinical Hospital	Dubrovnik
Croatia	Clinical Hospital	Osijek
Croatia	Clinical Hospital Split	Split
Croatia	Clinic for Pulmonary Diseses "Jordanovac"	Zagreb
Hungary	St. George County Hospital	Fejer County
Hungary	University of Szeged	Szeged
Hungary	General Rehablitation and Medicinal Bath Hospital	Szombathely
India	Gujrat Cancer Research Institute	Asarwa	Ahmadabad
India	Curie Centre of Oncology	Bangalore
India	Kidwai Memorial Institute of Oncology	Bangalore	Karnataka
India	Jawaharlal Nehru Cancer Hospital and Research Centre	Bhopal
India	Apollo Speciality Hospital	Chennai
India	Indo American Institute of Oncology	Hyderabaad
India	MNJ Institute of Oncology	Hyderabaad
India	Yashoda Group of Hospitals	Hyderabad
India	SEAROC Cancer Center	Jaipur
India	Lakeshore Hospital and Research Center	Kochin	Kerala
India	Institute of Post Graduate Medical Education and Research	Kolkata
India	Orchid Nursing Home	Kolkata
India	King George Medical University	Lucknow
India	KMC (Karturba Medical College) Hospital	Manipal
India	Jaslok Hospital and Research Centre	Mumbai
India	Tata Memorial Centre	Mumbai
India	Shatabdi Superspeciality Hospital	Nasik	Maharashtra
India	Rajiv Gandhi Cancer Institute, Delhi	New Delhi
India	Sir Ganga Ram Hospital	New Delhi
India	Mahaveer Cancer Sansthan	Patna
India	Jahangir Hospital and Research Centre	Pune
India	Smt. Vasantben R. Desai Cancer Research Center	Rajkot
India	Regional Cancer Centre	Trivandrum
India	King George Hospital	Vishakhapatnam
Latvia	Daugavas Hospital	Daugavpils
Latvia	Paul Stradins Clincial University Hospital	Riga
Montenegro	Special Hospital for Pulmonary Diseases	Niksic
Poland	Kujawsko-Pomorski Centre of Pulmonology	Bydgoszcz
Poland	NMP, Memorial Voyvodship Hospital	Czestochowa
Poland	Dr. Bieganski Memorial Regional Specialsitic Hospital	Grudziadz
Poland	Regional Hospital, Department of Pulmonary Diseases and Chemotherapy	Krakow
Poland	Independent Public Group for Tuberculosis and Lung Disease in Olsztyn	Olsztyn
Poland	Conservative Outpatient Oncology Department, Voyevodship Hospital in Plock	Plock
Poland	Department of Clinical Oncology, Wielkopolskie Centre of Lung Diseases and Tuberculosis	Poznan
Poland	Department of Pulmonology, Voyvodship Specialsitic Hospital in Radom	Radom
Poland	SP ZOZ Voyevodship Specialistic Hospital #3	Rybnik
Poland	Department of Chemotherapy, Prof. A. Sokolowski Memorial Specialistic Hospital in Szczecin	Szczecin
Poland	Department of Clinical Oncology, SP ZOZ, Yoyvodship Specialistic Hospital	Torun
Poland	Dolnoslaskie Centre of Lung Diseases	Wroclaw	Dolnoslaskie
Poland	Silesian Medical University in Katowice	Zabrze	Dolny Slask
Romania	Baia Mare "Constantin Opris" County Emergency Hospital	Baia Mare	Maramures County
Romania	Bucharest Institute of Oncology	Bucharest
Romania	IANULI Medconsult SRL	Bucharest
Romania	Prof. Dr. Ion Chircuta, Oncology Institute	Cluj-Napoca
Romania	Prof. Dr. Ion Chiricuta, Institute of Oncology Cluj-Napoca	Cluj-Napoca	Cluj
Romania	Clinical Emergency County Hospital Constanta	Constanta
Romania	Medical Oncology Center Iasi	Iasi
Romania	Schuller Municipal Hospital Ploiesti-Medical Oncology Department	Ploiesti
Romania	Clinical County Hospital	Sibiu
Romania	Sf. loan cel Nou, Emergency County Hospital	Suceava
Romania	OncoMed	Timisoara
Russian Federation	Arkhangelsk Regional Clinical Oncology Center	Arkhangelsk
Russian Federation	Altai Regional Oncology Center	Barnaul
Russian Federation	Regional Oncology Center	Birobidzhan	Jewish Republic
Russian Federation	Chelyabinsk Regional Oncology Center	Chelyabinsk
Russian Federation	City Hospital #1	Cherepovets
Russian Federation	Chita Regional Oncology Center	Chita
Russian Federation	Sverdlovsk Regional Oncology Center	Ekaterinburg
Russian Federation	Regional Oncology Center	Engels
Russian Federation	Regional Oncology Center	Irkutsk
Russian Federation	Ivanovo Regional Oncology Center	Ivanovo
Russian Federation	Republican Clinical Oncology Center of the Republic of Udmurtia	Izhevsk
Russian Federation	Kaluga Regional Oncology Center	Kaluga
Russian Federation	Clinical Oncology Center	Kazan	Tatarstan Republic
Russian Federation	Kazan Oncology Center	Kazan	Tatarstan Republic
Russian Federation	Regional Clinical Oncology Center	Khabarovsk
Russian Federation	Regional Clinical Oncology Center	Kirov
Russian Federation	City Oncology Center	Komsomolsk-na-Amure
Russian Federation	Krasnodar Clinical Oncology	Krasnodar
Russian Federation	Regional Clinical Hospital #1	Krasnodar
Russian Federation	Kurst Regional Oncology Center	Kurst
Russian Federation	Lipetsk Regional Oncology Center	Lipetsk
Russian Federation	Magnitogorsk Clinical Oncology Hospital	Magnitogorsk
Russian Federation	Blokhin Russian Oncology Research Center	Moscow
Russian Federation	Central Clinical Hospital and Outpatient Unit of the Medical Center under the Russian Presidential Administration	Moscow
Russian Federation	Semashko Central Clinical Hospital #2 under Russian Railways	Moscow
Russian Federation	Novorossiysk Oncology Center	Novorossiysk
Russian Federation	City Clinical Hospital #1	Novosibirsk
Russian Federation	Medical Radiology Research Center under RAMS	Obnninsk
Russian Federation	Orel Oncology Center	Orel
Russian Federation	Orenburg Regional Clinical Oncology Center	Orenburg
Russian Federation	Regional Oncology Center	Penza
Russian Federation	Republican Oncology Center of the Ministry of Healthcare of Karelia Republic	Petrozavodsk	Karelia Republic
Russian Federation	Pyatigorsk Affiliate of Stavropol Regional Clinical Oncology Center	Pyatigorsk
Russian Federation	Ogarev Mordovian State University	Saransk
Russian Federation	State Higher Education Institution Saratov State Medical University under the Federal Agency for Healthcare and Social Development	Saratov
Russian Federation	Oncology Center	Sochi
Russian Federation	City Clinical Oncology Center, Thoracic Oncology Department #6	St. Petersburg
Russian Federation	Pavlov St. Petersburg State Medical University, Pulmonology Research Institute	St. Petersburg
Russian Federation	St. Petersburg City Multifield Hospital #2	St. Petersburg
Russian Federation	St. Petersburg Pavlov State Medical University	St. Petersburg
Russian Federation	Komi Republican Oncology Center	Syktyvkar	Komi Republic
Russian Federation	Tambov Regional Oncology Center	Tambov
Russian Federation	Tomsk Regional Oncology Center	Tomsk
Russian Federation	Tula Regional Oncology Center	Tula
Russian Federation	Ufa, Republican Oncology Center	Ufa
Russian Federation	Buryatia Republican Oncology Center	Ulan-Ude	Buryatia
Russian Federation	Primorsky Regional Oncology Center	Vladivostok
Russian Federation	Volgograd Regional Clinical Oncology Center#1	Volograd
Russian Federation	Voronezh Regional Clinical Oncology Center	Voronezh
Russian Federation	Regional Clinical Oncology Hospital	Yaroslavl
Russian Federation	Republican of Clinical Hospital, Mariy-El Republican	Yoshkar-Ola
Serbia	Clinic for Pulmonary Diseases and TBC	Knez Selo
Serbia	Institute for Pulmonary Diseases of Vijvodina	Vijvodina
Ukraine	Volyn Regional Oncology Center	Lutsk
Ukraine	Public Treatment and Prevention Institution Mariupol City Interdistrict Oncology Center	Mariupol
Ukraine	Sumy Regional Oncology Center	Sumy
Ukraine	Ternopol Regional Clinical Oncology Center	Ternopol
Ukraine	Zaporozhye Regional Clinical Oncology Center	Zaporozhye

Sponsors (1)

Lead Sponsor	Collaborator
Poniard Pharmaceuticals

Countries where clinical trial is conducted

Argentina,  Belarus,  Bosnia and Herzegovina,  Bulgaria,  Chile,  Croatia,  Hungary,  India,  Latvia,  Montenegro,  Poland,  Romania,  Russian Federation,  Serbia,  Ukraine, 

References & Publications (10)

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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. — View Citation

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. — 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

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. — View Citation

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. — 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

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall survival		death	No
Secondary	objective response rate		progression	No
Secondary	disease control rate		progression	No
Secondary	duration of response		progression	No
Secondary	progression-free survival		death	No