Clinical trial NCT00465491: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Small Cell Lung Cancer
Keywords: refractory
chemotherapy
progressed
second-line treatment
small cell lung cancer
best supportive care
picoplatin
Lead sponsor: Poniard Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-04-25
Enrollment: 399
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: overall survival
timeFrame: death
Secondary outcomes:
measure: objective response rate
timeFrame: progression
measure: disease control rate
timeFrame: progression
measure: duration of response
timeFrame: progression
measure: progression-free survival
timeFrame: death
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Consultorios Privados
city: Buenos Aires
country: Argentina
facility: Clinica Constituyentes
city: Buenos Aires
country: Argentina
facility: CETEN Centro de Estudio y Tratamiento de Enfermedades Neoplasicas
city: Buenos Aires
country: Argentina
facility: IADT (Insttituto Argentino de Diagnostico y Tratamiento S.A.)
city: Buenos Aires
country: Argentina
facility: Centro Oncologico
city: Buenos Aires
country: Argentina
facility: Instituto Alexander Fleming
city: Buenos Aires
country: Argentina
facility: PALIAR
city: Cordoba
country: Argentina
facility: IONC
city: Santa Fe
country: Argentina
facility: Centro Oncologico de Rosario
city: Santa Fe
country: Argentina
facility: ISIS Clinica Especializada
city: Tucuman
country: Argentina
facility: Centro Medico San Roque
city: Gomel
country: Belarus
facility: Gomel Regional Oncological Dispensary
city: Grodno
country: Belarus
facility: Institution of Healthcare "Grodno Regional Clinical Hospital
city: Minsk
country: Belarus
facility: Minsk City Clinical Oncology Dispensary
city: Minsk
country: Belarus
facility: Research Institute of Oncology and Medical Radiology named by N.N. Aleksandrov
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Oncology Dispensary
city: Banja Luka
country: Bosnia and Herzegovina
facility: Clinic for Lung Diseases, Clinical Center, Banja Luka
city: Sarajevo
country: Bosnia and Herzegovina
facility: Clinic of Pulmonary Diseases Podhrastovi
city: Gabrovo
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment, Dr. Tota Venkova
city: Pleven
country: Bulgaria
facility: University Multifunctional Hospital for Active Treatment "Dr. Georgi Stranski"
city: Plovdiv
country: Bulgaria
facility: District Dispensary for Cancer Diseases with Inpatient Hospital Plovdiv
city: Rousse
country: Bulgaria
facility: Regional Oncodispensary with Inpatient Sector
city: Shumen
country: Bulgaria
facility: Inter-district Dispensary for Cancer Diseases w/Inpatient Hospital
city: Sofia
country: Bulgaria
facility: Regional Oncodispensary with Inpatient Sector-Sofia District
city: Varna
country: Bulgaria
facility: Inter-district Dispensary for Cancer Disease w/Inpatient Hospital "Dr. Marko Markov", Varna
city: Varna
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "St. Marina"
city: Santiago
country: Chile
facility: Instituto Nacional de Cancer
city: Dubrovnik
country: Croatia
facility: Clinical Hospital
city: Osijek
country: Croatia
facility: Clinical Hospital
city: Split
country: Croatia
facility: Clinical Hospital Split
city: Zagreb
country: Croatia
facility: Clinic for Pulmonary Diseses "Jordanovac"
city: Fejer County
country: Hungary
facility: St. George County Hospital
city: Szeged
country: Hungary
facility: University of Szeged
city: Szombathely
country: Hungary
facility: General Rehablitation and Medicinal Bath Hospital
city: Asarwa
country: India
facility: Gujrat Cancer Research Institute
state: Ahmadabad
city: Bangalore
country: India
facility: Kidwai Memorial Institute of Oncology
state: Karnataka
city: Kochin
country: India
facility: Lakeshore Hospital and Research Center
state: Kerala
city: Nasik
country: India
facility: Shatabdi Superspeciality Hospital
state: Maharashtra
city: Bangalore
country: India
facility: Curie Centre of Oncology
city: Bhopal
country: India
facility: Jawaharlal Nehru Cancer Hospital and Research Centre
city: Chennai
country: India
facility: Apollo Speciality Hospital
city: Hyderabaad
country: India
facility: MNJ Institute of Oncology
city: Hyderabaad
country: India
facility: Indo American Institute of Oncology
city: Hyderabad
country: India
facility: Yashoda Group of Hospitals
city: Jaipur
country: India
facility: SEAROC Cancer Center
city: Kolkata
country: India
facility: Institute of Post Graduate Medical Education and Research
city: Kolkata
country: India
facility: Orchid Nursing Home
city: Lucknow
country: India
facility: King George Medical University
city: Manipal
country: India
facility: KMC (Karturba Medical College) Hospital
city: Mumbai
country: India
facility: Jaslok Hospital and Research Centre
city: Mumbai
country: India
facility: Tata Memorial Centre
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
city: New Delhi
country: India
facility: Rajiv Gandhi Cancer Institute, Delhi
city: Patna
country: India
facility: Mahaveer Cancer Sansthan
city: Pune
country: India
facility: Jahangir Hospital and Research Centre
city: Rajkot
country: India
facility: Smt. Vasantben R. Desai Cancer Research Center
city: Trivandrum
country: India
facility: Regional Cancer Centre
city: Vishakhapatnam
country: India
facility: King George Hospital
city: Daugavpils
country: Latvia
facility: Daugavas Hospital
city: Riga
country: Latvia
facility: Paul Stradins Clincial University Hospital
city: Niksic
country: Montenegro
facility: Special Hospital for Pulmonary Diseases
city: Wroclaw
country: Poland
facility: Dolnoslaskie Centre of Lung Diseases
state: Dolnoslaskie
city: Zabrze
country: Poland
facility: Silesian Medical University in Katowice
state: Dolny Slask
city: Bydgoszcz
country: Poland
facility: Kujawsko-Pomorski Centre of Pulmonology
city: Czestochowa
country: Poland
facility: NMP, Memorial Voyvodship Hospital
city: Grudziadz
country: Poland
facility: Dr. Bieganski Memorial Regional Specialsitic Hospital
city: Krakow
country: Poland
facility: Regional Hospital, Department of Pulmonary Diseases and Chemotherapy
city: Olsztyn
country: Poland
facility: Independent Public Group for Tuberculosis and Lung Disease in Olsztyn
city: Plock
country: Poland
facility: Conservative Outpatient Oncology Department, Voyevodship Hospital in Plock
city: Poznan
country: Poland
facility: Department of Clinical Oncology, Wielkopolskie Centre of Lung Diseases and Tuberculosis
city: Radom
country: Poland
facility: Department of Pulmonology, Voyvodship Specialsitic Hospital in Radom
city: Rybnik
country: Poland
facility: SP ZOZ Voyevodship Specialistic Hospital #3
city: Szczecin
country: Poland
facility: Department of Chemotherapy, Prof. A. Sokolowski Memorial Specialistic Hospital in Szczecin
city: Torun
country: Poland
facility: Department of Clinical Oncology, SP ZOZ, Yoyvodship Specialistic Hospital
city: Cluj-Napoca
country: Romania
facility: Prof. Dr. Ion Chiricuta, Institute of Oncology Cluj-Napoca
state: Cluj
city: Baia Mare
country: Romania
facility: Baia Mare "Constantin Opris" County Emergency Hospital
state: Maramures County
city: Bucharest
country: Romania
facility: IANULI Medconsult SRL
city: Bucharest
country: Romania
facility: Bucharest Institute of Oncology
city: Cluj-Napoca
country: Romania
facility: Prof. Dr. Ion Chircuta, Oncology Institute
city: Constanta
country: Romania
facility: Clinical Emergency County Hospital Constanta
city: Iasi
country: Romania
facility: Medical Oncology Center Iasi
city: Ploiesti
country: Romania
facility: Schuller Municipal Hospital Ploiesti-Medical Oncology Department
city: Sibiu
country: Romania
facility: Clinical County Hospital
city: Suceava
country: Romania
facility: Sf. loan cel Nou, Emergency County Hospital
city: Timisoara
country: Romania
facility: OncoMed
city: Ulan-Ude
country: Russian Federation
facility: Buryatia Republican Oncology Center
state: Buryatia
city: Birobidzhan
country: Russian Federation
facility: Regional Oncology Center
state: Jewish Republic
city: Petrozavodsk
country: Russian Federation
facility: Republican Oncology Center of the Ministry of Healthcare of Karelia Republic
state: Karelia Republic
city: Syktyvkar
country: Russian Federation
facility: Komi Republican Oncology Center
state: Komi Republic
city: Kazan
country: Russian Federation
facility: Clinical Oncology Center
state: Tatarstan Republic
city: Kazan
country: Russian Federation
facility: Kazan Oncology Center
state: Tatarstan Republic
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Oncology Center
city: Barnaul
country: Russian Federation
facility: Altai Regional Oncology Center
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Oncology Center
city: Cherepovets
country: Russian Federation
facility: City Hospital #1
city: Chita
country: Russian Federation
facility: Chita Regional Oncology Center
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Oncology Center
city: Engels
country: Russian Federation
facility: Regional Oncology Center
city: Irkutsk
country: Russian Federation
facility: Regional Oncology Center
city: Ivanovo
country: Russian Federation
facility: Ivanovo Regional Oncology Center
city: Izhevsk
country: Russian Federation
facility: Republican Clinical Oncology Center of the Republic of Udmurtia
city: Kaluga
country: Russian Federation
facility: Kaluga Regional Oncology Center
city: Khabarovsk
country: Russian Federation
facility: Regional Clinical Oncology Center
city: Kirov
country: Russian Federation
facility: Regional Clinical Oncology Center
city: Komsomolsk-na-Amure
country: Russian Federation
facility: City Oncology Center
city: Krasnodar
country: Russian Federation
facility: Krasnodar Clinical Oncology
city: Krasnodar
country: Russian Federation
facility: Regional Clinical Hospital #1
city: Kurst
country: Russian Federation
facility: Kurst Regional Oncology Center
city: Lipetsk
country: Russian Federation
facility: Lipetsk Regional Oncology Center
city: Magnitogorsk
country: Russian Federation
facility: Magnitogorsk Clinical Oncology Hospital
city: Moscow
country: Russian Federation
facility: Blokhin Russian Oncology Research Center
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital and Outpatient Unit of the Medical Center under the Russian Presidential Administration
city: Moscow
country: Russian Federation
facility: Semashko Central Clinical Hospital #2 under Russian Railways
city: Novorossiysk
country: Russian Federation
facility: Novorossiysk Oncology Center
city: Novosibirsk
country: Russian Federation
facility: City Clinical Hospital #1
city: Obnninsk
country: Russian Federation
facility: Medical Radiology Research Center under RAMS
city: Orel
country: Russian Federation
facility: Orel Oncology Center
city: Orenburg
country: Russian Federation
facility: Orenburg Regional Clinical Oncology Center
city: Penza
country: Russian Federation
facility: Regional Oncology Center
city: Pyatigorsk
country: Russian Federation
facility: Pyatigorsk Affiliate of Stavropol Regional Clinical Oncology Center
city: Saransk
country: Russian Federation
facility: Ogarev Mordovian State University
city: Saratov
country: Russian Federation
facility: State Higher Education Institution Saratov State Medical University under the Federal Agency for Healthcare and Social Development
city: Sochi
country: Russian Federation
facility: Oncology Center
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg City Multifield Hospital #2
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg Pavlov State Medical University
city: St. Petersburg
country: Russian Federation
facility: Pavlov St. Petersburg State Medical University, Pulmonology Research Institute
city: St. Petersburg
country: Russian Federation
facility: City Clinical Oncology Center, Thoracic Oncology Department #6
city: Tambov
country: Russian Federation
facility: Tambov Regional Oncology Center
city: Tomsk
country: Russian Federation
facility: Tomsk Regional Oncology Center
city: Tula
country: Russian Federation
facility: Tula Regional Oncology Center
city: Ufa
country: Russian Federation
facility: Ufa, Republican Oncology Center
city: Vladivostok
country: Russian Federation
facility: Primorsky Regional Oncology Center
city: Volograd
country: Russian Federation
facility: Volgograd Regional Clinical Oncology Center#1
city: Voronezh
country: Russian Federation
facility: Voronezh Regional Clinical Oncology Center
city: Yaroslavl
country: Russian Federation
facility: Regional Clinical Oncology Hospital
city: Yoshkar-Ola
country: Russian Federation
facility: Republican of Clinical Hospital, Mariy-El Republican
city: Knez Selo
country: Serbia
facility: Clinic for Pulmonary Diseases and TBC
city: Vijvodina
country: Serbia
facility: Institute for Pulmonary Diseases of Vijvodina
city: Lutsk
country: Ukraine
facility: Volyn Regional Oncology Center
city: Mariupol
country: Ukraine
facility: Public Treatment and Prevention Institution Mariupol City Interdistrict Oncology Center
city: Sumy
country: Ukraine
facility: Sumy Regional Oncology Center
city: Ternopol
country: Ukraine
facility: Ternopol Regional Clinical Oncology Center
city: Zaporozhye
country: Ukraine
facility: Zaporozhye Regional Clinical Oncology Center
Study officials:
affiliation: Poniard Pharmaceuticals
name: Dr. Hazel Breitz, M.D.
role: STUDY_DIRECTOR
References:
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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.
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. doi: 10.1038/bjc.1998.59.
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. doi: 10.1016/s0959-8049(02)00107-7.
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. doi: 10.1016/s0959-8049(02)00244-7.
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. doi: 10.1016/s0169-5002(02)00175-7.