Clinical trial NCT02609828: Phase 3 Study on the Efficacy and Safety of Tanezumab in Patients With Cancer Pain Due to Bone Metastasis Who Are Taking Background Opioid Therapy
Official title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF THE SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB (PF-04383119) IN SUBJECTS WITH CANCER PAIN PREDOMINANTLY DUE TO BONE METASTASIS RECEIVING BACKGROUND OPIOID THERAPY
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bone Metastasis
Cancer Pain
Keywords: Metastatic cancer bone pain
Multiple myeloma
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2015-11-20
Enrollment: 156
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: The purpose of this study is to determine whether tanezumab is effective in the treatment of cancer pain due to bone metastasis in patients already taking background opioid therapy.

Detailed description: This is a randomized, double-blind, placebo-controlled, multicenter, parallel-group Phase 3 study in cancer subjects requiring treatment with background opioids for pain due to bone metastasis.

Approximately 144 subjects will be randomized to one of 2 treatment groups in a 1:1 ratio (approximately 72 subjects per group). Subjects will receive a total of 3 subcutaneous injections, separated by 8 weeks in addition to background opioids administered throughout the study.

Treatment groups will include: 1. Placebo SC (matching tanezumab SC) in addition to background opioid therapy. 2. Tanezumab 20 mg SC in addition to background opioid therapy.

The study consists of three periods: Pre-Treatment (up to 37 days), Double-Blind Treatment (24 weeks) and Safety Follow-up (24 weeks).

Eligibility criteria: Inclusion Criteria:

* Personally signed and dated informed consent document.
* Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
* Male or female, ≥18 years of age
* Weight ≥40 kg at Screening
* Cancer diagnosed as having metastasized to bone or multiple myeloma.
* Imaging confirmation of bone metastasis at Screening or within 120 days prior to the Screening visit.
* Expected to require daily opioid medication throughout the course of the study.
* Willing to not use prohibited medications (including NSAIDs) throughout the duration of the study.
* Average Pain Score ≥5 at Screening for the index bone metastasis cancer pain site.
* Patient's Global Assessment of Cancer Pain of "fair", "poor" or "very poor" at Screening.
* Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0, 1, or 2 at Screening.
* Adequate bone marrow, renal and liver function at Screening.
* International Normalized Ratio (INR) or prothrombin time (PT) \<1.5 x ULN at Screening unless being treated with anticoagulant medication.
* Females must either be not of childbearing potential or, if of childbearing potential and at risk for pregnancy, must be willing to use at least one highly effective method of contraception throughout the study and for 112 days (16 weeks) after the last dose of assigned subcutaneous study medication.

Exclusion Criteria:

* Pain related to an oncologic emergency.
* Brain metastasis or leptomeningeal metastasis.
* Presence of hypercalcemia at Screening.
* Pain primarily classified as not predominantly related to a bone metastasis.
* Systemic treatment for the primary malignancy or bone metastasis started within 30 days of the Baseline Assessment Period.
* Chemotherapies associated with peripheral neuropathy (ie, paclitaxel, docetaxel, oxaliplatin, cisplatin, vincristine, thalidomide or bortezomib) are prohibited during the study from 30 days prior to the first day of the Baseline Assessment Period to Week 48.
* Receipt of radiopharmaceutical treatment or radiotherapy for treatment of bone metastasis within 30 days of the Baseline Assessment Period.
* Concurrent adjuvant analgesics unless started at least 30 days prior to the start of the Baseline Assessment Period and maintained at a stable dose.
* Diagnosis of osteoarthritis of the knee or hip or findings consistent with osteoarthritis in the shoulder.
* History of significant trauma or surgery to a major joint within one year prior to Screening.
* History of osteonecrosis or osteoporotic fracture.
* X-ray evidence at Screening of: 1) rapidly progressive osteoarthritis, 2) atrophic or hypotrophic osteoarthritis, 3) subchondral insufficiency fracture, 4) spontaneous osteonecrosis of the knee (SPONK), 5) osteonecrosis, or 6) pathologic fracture.
* Signs and symptoms of clinically significant cardiac disease.
* Evidence of orthostatic hypotension at Screening or at Baseline prior to randomization.
* Diagnosis of a transient ischemic attack in the 6 months prior to Screening or diagnosis of stroke with significant residual deficits.
* History, diagnosis, or signs and symptoms of clinically significant neurological disease.
* Total impact score of \>7 on the Survey of Autonomic Symptoms (SAS) at Screening.
* Past history of carpal tunnel syndrome (CTS) with signs or symptoms of CTS in the one year prior to Screening.
* History of significant alcohol, analgesic, or narcotic substance abuse within the six months prior to Screening.
* Planned surgical procedure during the duration of the study.
* Considered unfit for surgery or not willing to undergo joint replacement surgery if required.
* Known hypersensitivity to opioids or an underlying medical condition contraindicating opioid use.
* History of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG-fusion protein.
* Previous exposure to exogenous nerve growth factor or to an anti-nerve growth factor antibody.
* Presence of drugs of abuse, prescription medications without a valid prescription or other illegal drugs at Screening.
* Positive Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV) tests at Screening indicative of current infection.
* Investigational site staff members and their family members, or Pfizer employees directly involved in the conduct of the trial.
* Participation in other studies involving investigational drug(s) within 30 days (or 90 days for investigational biologics) before Baseline Assessment Period and/or during study participation.
* Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential who are unwilling or unable to use one (1) highly effective method of contraception throughout the study and for 112 days after last dose of investigational product.
* Other severe acute or chronic medical or psychiatric condition or laboratory abnormality.

Primary outcomes:
measure: Change From Baseline in the Daily Average Pain Intensity Numerical Rating Score (NRS) in the Index Bone Metastasis Cancer Pain Site at Week 8
timeFrame: Baseline, Week 8
Secondary outcomes:
measure: Change From Baseline in the Daily Average Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 12, 16 and 24
timeFrame: Baseline, Weeks 1, 2, 4, 6, 12, 16 and 24
measure: Change From Baseline in the Daily Worst Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
timeFrame: Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24
measure: Change From Baseline in the Weekly Average Pain Intensity NRS Score in Non-Index Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
timeFrame: Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24
measure: Change From Baseline in the Weekly Worst Pain Intensity NRS Score in Non-Index Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
timeFrame: Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24
measure: Change From Baseline in the Daily Average Pain Intensity NRS Score in the Non-Index Visceral Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
timeFrame: Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24
measure: Change From Baseline in the Daily Worst Pain Intensity NRS Score in the Non-Index Visceral Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
timeFrame: Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24
measure: Number of Participants With Cumulative Reduction of >=30, 50, 70 and 90 Percent (%) From Baseline in Daily Average Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
timeFrame: Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24
measure: Number of Participants With Reduction of >=30, 50, 70 and 90% From Baseline in Daily Worst Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
timeFrame: Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24
measure: Change From Baseline in Participant's Global Assessment of Cancer Pain (PGA-CP) at Weeks 2, 4, 8, 16 and 24
timeFrame: Baseline, Weeks 2, 4, 8, 16 and 24
measure: Number of Participants With Reduction of >=2 Points From Baseline in PGA-CP Scores at Weeks 2, 4, 8, 16 and 24
timeFrame: Baseline, Weeks 2, 4, 8, 16 and 24
measure: Average Daily Total Opioid Consumption at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
timeFrame: Weeks 1, 2, 4, 6, 8, 12, 16 and 24
measure: Average Number of Doses of Rescue Opioid Consumption at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
timeFrame: Weeks 1, 2, 4, 6, 8, 12, 16 and 24
measure: Change From Baseline in the Weekly Opioid-Related Symptom Distress Scale (OR-SDS) at Weeks 2, 4, 8, 16, and 24
timeFrame: Baseline, Weeks 2, 4, 8, 16, and 24
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1 of dosing up to 24 weeks post last dose (maximum up to Week 48)
measure: Number of Participants With Laboratory Abnormalities (Normal Baseline)
timeFrame: Baseline (Day 1, before dosing) up to Week 48
measure: Number of Participants With Laboratory Abnormalities (Abnormal Baseline)
timeFrame: Baseline (Day 1, before dosing) up to Week 48
measure: Number of Participants With Categorical Change From Baseline to Last Post-Baseline in Sitting Systolic and Diastolic Blood Pressure During Treatment Period
timeFrame: Baseline (Day 1, before dosing) up to Week 24
measure: Number of Participants With Categorical Summary of Electrocardiogram (ECG) (QTC) Data
timeFrame: Baseline (Day 1, before dosing) up to Week 24
measure: Number of Participants With Confirmed Orthostatic Hypotension
timeFrame: Baseline (Day 1, before dosing), Weeks 8, 16, 24 and 48
measure: Number of Participants With Clinically Significant Findings in Weight Measurement, Counted as an AE
timeFrame: Day 1 of dosing up to maximum of Week 48
measure: Number of Participants With Abnormal Physical Examination at Screening
timeFrame: Screening (up to 37 days prior to Day 1)
measure: Number of Participants With Individual Adjudicated Joint Safety Outcome/Event
timeFrame: During the study, maximum up to Week 48
measure: Number of Participants With At Least 1 Total Joint Replacements (TJR)
timeFrame: During the study, maximum up to Week 48
measure: Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Anti-Drug Antibodies (NAb)
timeFrame: Baseline (Day 1, before dosing) up to Week 48
Other outcomes:
Locations:
city: Rosario
country: Argentina
facility: Instituto de Oncologia de Rosario
state: Santa FE
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: East Bentleigh
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Krems
country: Austria
facility: Landesklinikum Krems
city: Senftenberg
country: Austria
facility: Nuhr Medical Center
city: Ijui
country: Brazil
facility: Associacao Hospital de Caridade de Ijui
state: RIO Grande DO SUL
city: Rio de Janeiro
country: Brazil
facility: INCA - Instituto Nacional do Cancer / Hospital do Cancer HCIII
state: RJ
city: Barretos
country: Brazil
facility: Fundação Pio XII-Hospital de Cancer de Barretos
state: SAO Paulo
city: Jau
country: Brazil
facility: Centro de Ensino e Pesquisa da Fundacao Amaral Carvalho
state: SAO Paulo
city: Santo Andre
country: Brazil
facility: Fundacao do ABC - Faculdade de Medicina do ABC - CEPHO
state: SAO Paulo
city: Itajai
country: Brazil
facility: Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral
state: SC
city: Santo Andre
country: Brazil
facility: Fundacao do ABC-Faculdade de Medicina do ABC
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital AC Camargo_Fundacao Antonio Prudente
state: SP
city: Sao Paulo
country: Brazil
facility: Centro de Pesquisa Clinica do IBCC - Instituto Brasileiro de Controle do Cancer
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital AC Camargo_Fundacao Antonio Prudente
city: Araucania
country: Chile
facility: James Lind Centro de lnvestigacion del Cancer
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University, Department of Medical Oncology
state: Anhui
city: Beijing
country: China
facility: The Fifth Medical Center of PLA General Hospital
state: Beijing
city: Chongqing
country: China
facility: Daping Hospital, Research Institute of Surgery Third Military Medical University
state: Chongqing
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital/Oncology Department
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital/Respiration internal medicine
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology/Cancer Center
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
state: Shanghai
city: Chengdu
country: China
facility: Oncology Department, West China Hospital of Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Plzen
country: Czechia
facility: Urocentrum Plzen Research Site s.r.o.
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze, Fakultni poliklinika, Centrum pro lecbu bolesti
city: Farkasgyepu
country: Hungary
facility: Veszprem Megyei Tudogyogyintezet Farkasgyepu
city: Miskolc
country: Hungary
facility: CRU Hungary Ltd., MISEK Hematology Department-CRU Co.
city: Miskolc
country: Hungary
facility: CRU Hungary Ltd., MISEK-CRU
city: Nyiregyhaza
country: Hungary
facility: Josa Andras Hospital, Clinical Research Department
city: Nyiregyhaza
country: Hungary
facility: Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
city: Szekesfehervar
country: Hungary
facility: Help-MR Diagnosztika Kft.
city: Afula
country: Israel
facility: HaEmek Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Toyohashi
country: Japan
facility: National Hospital Organization Toyohashi Medical Center
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Ota
country: Japan
facility: Gunma Prefectural Cancer Center
state: Gunma
city: Nishinomiya
country: Japan
facility: Nishinomiya Municipal Central Hospital
state: Hyogo
city: Nishinomiya
country: Japan
facility: The Hospital of Hyogo College of Medicine
state: Hyogo
city: Saga
country: Japan
facility: Saga-Ken Medical Centre Koseikan
city: Tokyo
country: Japan
facility: National Hospital Organization Tokyo Medical Center
city: Goyang-si
country: Korea, Republic of
facility: Clinical Trial Pharmacy, National Cancer Center
state: Gyeonggi-do
city: Goyang-si
country: Korea, Republic of
facility: Imaging Facilities, National Cancer Center
state: Gyeonggi-do
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Pharmacy, Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Imaging Facilities, Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Bedzin
country: Poland
facility: Powiatowy Zespol Zakladow Opieki Zdrowotnej Oddzial Opieki Paliatywnej
city: Bialystok
country: Poland
facility: NZOZ Vitamed im. Edyty Jakubow
city: Bialystok
country: Poland
facility: Poradnia Otropedyczno-Urazowa; Gabient RTG
city: Czeladz
country: Poland
facility: Pracownia RTG Helimed
city: Dabrowa Gornicza
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej, Zespol Medyczno-Opiekunczy Alicja Kluczna
city: Gdansk
country: Poland
facility: Hospicjum im. Ks. Eugeniusza Dutkiewicza SAC w Gdansku
city: Gliwice
country: Poland
facility: Stowarzyszenie Przyjaciol Chorych Hospicjum w Gliwicach NZOZ Hospicjum Milosierdzia Bozego
city: Gliwice
country: Poland
facility: Stowarzyszenie Przyjaciol Chorych Hospicjum w Gliwicach, NZOZ Hospicjum Milosierdzia Bozego
city: Grudziadz
country: Poland
facility: Regionalny Szpital Specjalistyczny im. Dr. Wl.Bieganskiego, Oddzial Onkologii Klinicznej
city: Katowice
country: Poland
facility: SCANiX Sp.z o.o
city: Katowice
country: Poland
facility: NZOZ "Vegamed"
city: Katowice
country: Poland
facility: Helimed Diagnostic Imaging Sp. z o.o., Sp. komandytowa
city: Katowice
country: Poland
facility: Helimed Diagnostic Imaging Sp. z.o.o., Sp. komandytowa
city: Katowice
country: Poland
facility: Centrum Diagnostyki Obrazowej EPIONE
city: Lublin
country: Poland
facility: NZOZ Neuromed M. i M. Nastaj Sp. P.
city: Poznan
country: Poland
facility: SK Przemienienia Panskiego UM im. Karola Marcinkowskiego w Poznaniu,
city: Warszawa
country: Poland
facility: Klinika Nowotworow Piersi i Chirurgii Rekonstrukcyjnej w Centrum Onkologii -Instytucie
city: Warszawa
country: Poland
facility: Szpital LUX MED
city: Craiova
country: Romania
facility: SC Oncolab SRL
state: Dolj
city: Timisoara
country: Romania
facility: S.C. Oncocenter Oncologie Clinica S.R.L.
state: Timis
city: Bucuresti
country: Romania
facility: Spitalul Clinic C.F. 2 Bucuresti. Departament Oncologie, Sectia Medicala 2
city: Bratislava
country: Slovakia
facility: Narodny onkologicky ustav
city: Nove Zamky
country: Slovakia
facility: DEMOMED s.r.o.
city: Pruske
country: Slovakia
facility: MUDr. Viliam Cibik, PhD, s.r.o.
city: Zilina
country: Slovakia
facility: Fakultna Nemocnica S Poliklinikou Zilina
city: Elche
country: Spain
facility: Hospital General Universitario de Elche Servicio de Farmacia
state: Alicante
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Ibiza
country: Spain
facility: Hospital Can Misses
state: Islas Baleares
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital La Moraleja
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Tooting
country: United Kingdom
facility: St George's University Hospitals NHS Foundation Trust
state: London
city: Edinburgh
country: United Kingdom
facility: NHS Lothian, Royal Infirmary of Edinburgh
state: Scotland
city: Edinburgh
country: United Kingdom
facility: NHS Lothian, Western General Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: NHS Lothian
state: Scotland
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: