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

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT02609828

Collaborator

Eli Lilly and Company (Industry)

156

Enrollment

Locations

Arms

67.9

Actual Duration (Months)

1.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bone Metastasis Cancer Pain	Drug: Tanezumab	Phase 3

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

156 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 28, 2015

Actual Primary Completion Date :

Sep 17, 2020

Actual Study Completion Date :

Jun 25, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 Tanezumab 20 mg subcutaneously	Drug: Tanezumab Subcutaneous study treatment (tanezumab 20 mg or matched placebo) dosed at 8 week intervals. Other Names: PF-04383119
Placebo Comparator: Arm 2 Placebo matched to active treatment subcutaneously	Drug: Tanezumab Subcutaneous study treatment (tanezumab 20 mg or matched placebo) dosed at 8 week intervals. Other Names: PF-04383119

Arm

Intervention/Treatment

Experimental: Arm 1

Tanezumab 20 mg subcutaneously

Drug: Tanezumab

Subcutaneous study treatment (tanezumab 20 mg or matched placebo) dosed at 8 week intervals.

Other Names:

PF-04383119

Placebo Comparator: Arm 2

Placebo matched to active treatment subcutaneously

Drug: Tanezumab

Subcutaneous study treatment (tanezumab 20 mg or matched placebo) dosed at 8 week intervals.

Other Names:

PF-04383119

Outcome Measures

Primary Outcome Measures

Change from baseline in daily average pain intensity in index bone metastasis cancer pain site [8 weeks]
Change from Baseline to Week 8 in the daily average pain intensity Numerical Rating Score (NRS) in the index bone metastasis cancer pain site.

Secondary Outcome Measures

Change from baseline in daily average pain intensity in index bone metastasis cancer pain site [Up to 24 weeks]
Change from Baseline to Weeks 1, 2, 4, 6, 12, 16 and 24 in the daily average pain intensity NRS score in the index bone metastasis cancer pain site.
Change from baseline in daily worst pain intensity in index bone metastasis cancer pain site [Up to 24 weeks]
Change from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 in the daily worst pain intensity NRS score in the index bone metastasis cancer pain site.
Change from baseline in weekly average pain intensity in non-index cancer pain sites [Up to 24 weeks]
Change from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 in the weekly average pain intensity NRS score in non-index cancer pain sites.
Change from baseline in weekly worst pain intensity in non-index cancer pain sites [Up to 24 weeks]
Change from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 in the weekly worst pain intensity NRS score in non-index cancer pain sites.
Change from baseline in daily average pain intensity in non-index visceral cancer pain sites [Up to 24 weeks]
Change from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 in the daily average pain intensity NRS score in the non-index visceral cancer pain sites.
Change from baseline in daily worst pain intensity in non-index visceral cancer pain sites [Up to 24 weeks]
Change from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 in the daily worst pain intensity NRS score in the non-index visceral cancer pain sites.
Change from baseline in Brief Pain Inventory (BPI) average pain score [Up to 24 weeks]
Change from Baseline to Weeks 2, 4, 8, 16 and 24 in the Brief Pain Inventory (BPI) average pain scores obtained at study visits.
Change from baseline in BPI worst pain score [Up to 24 weeks]
Change from Baseline to Weeks 2, 4, 8, 16 and 24 in the BPI worst pain scores obtained at study visits.
Response as defined by a 30%, 50%, 70%, and 90% reduction from Baseline in the daily average and daily worst pain intensity NRS score in the index bone metastasis cancer pain site [Up to 24 weeks]
Response as defined by a 30%, 50%, 70%, and 90% reduction from baseline in the daily average and 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.
Change from baseline in Patient's Global Assessment of Cancer Pain [Up to 24 weeks]
Change from Baseline in Patient's Global Assessment of Cancer Pain at Weeks 2, 4, 8, 16 and 24.
Response defined as an improvement of 2 points in Patient's Global Assessment of Cancer Pain [Up to 24 weeks]
Response defined as an improvement of 2 points in Patient's Global Assessment of Cancer Pain at Weeks 2, 4, 8, 16 and 24.
Change from baseline in the BPI Pain Interference with Function composite score and individual pain interference item scores [Up to 24 weeks]
Change from Baseline to Weeks 2, 4, 8, 16 and 24 in the BPI Pain Interference with Function Composite Score and individual pain interference item scores obtained at study visits.
EuroQol 5 Dimension (EQ-5D-5L) dimensions and overall health utility score [Up to 24 weeks]
EuroQol 5 Dimension (EQ-5D-5L) dimensions and overall health utility score at Baseline and Weeks 8, 16 and 24.
Average daily total opioid consumption (in mg of morphine equivalent doses) [Up to 24 weeks]
Average daily total opioid consumption (in mg of morphine equivalent doses) at Weeks 1, 2, 4, 6, 8, 12, 16 and 24.
Average number of doses of rescue medication required per week [Up to 24 weeks]
Average number of doses of rescue medication required per week at Weeks 1, 2, 4, 6, 8, 12, 16 and 24.
Change from baseline in weekly Opioid-Related Symptom Distress Scale [Up to 24 weeks]
Change from Baseline in the weekly Opioid-Related Symptom Distress Scale at Weeks 2, 4, 8, 16, and 24.
Adverse events [Up to 48 weeks]
Summary listing of adverse events for each participant; Summary of risk differences between each tanezumab group and placebo for common adverse events and for selected adverse events of interest.
Standard safety assessments [Up to 48 weeks]
Summary listing of safety laboratory testing [chemistry, hematology], sitting vital signs, ECG [12-lead]) for each participant.
Orthostatic (supine/standing) blood pressure assessment [Up to 48 weeks]
Orthostatic (supine/standing) blood pressure assessment.
Weight and Height measurements, Physical examinations. [Up to 48 weeks]
Weight measurements (pounds or kilograms), Height measurements (inches or centimeters), Body Mass Index (kg per meter squared), Physical examinations.
Neurologic examination (Neuropathy Impairment Score [NIS]). [Up to 48 weeks]
Neurologic examination (Neuropathy Impairment Score [NIS]).
Survey of Autonomic Symptom scores [Up to 48 weeks]
Survey of Autonomic Symptom scores.
Anti-drug antibody (ADA) assessments [Up to 48 weeks]
Anti-drug antibody (ADA) assessments.
Joint safety adjudication outcomes [Up to 48 weeks, or up to 24 weeks following total joint replacement procedure]
Number of subjects with adjudicated events of rapidly progressive osteoarthritis type 2, subchondral insufficiency fractures or spontaneous osteonecrosis of the knee, primary osteonecrosis, or pathological fracture.
Total joint replacements [Up to 24 weeks post-procedure]
Total joint replacements

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Instituto de Oncologia de Rosario	Rosario	Santa FE	Argentina	S2000KZE
2	Monash Medical Centre	Clayton	Victoria	Australia	3168
3	Monash Medical Centre	East Bentleigh	Victoria	Australia	3165
4	Landesklinikum Krems	Krems		Austria	3500
5	Nuhr Medical Center	Senftenberg		Austria	3541
6	Associacao Hospital de Caridade de Ijui	Ijui	RIO Grande DO SUL	Brazil	98700-000
7	INCA - Instituto Nacional do Cancer / Hospital do Cancer HCIII	Rio de Janeiro	RJ	Brazil	20560-120
8	Fundação Pio XII-Hospital de Cancer de Barretos	Barretos	SAO Paulo	Brazil	14.784-400
9	Centro de Ensino e Pesquisa da Fundacao Amaral Carvalho	Jau	SAO Paulo	Brazil	17210-120
10	Fundacao do ABC - Faculdade de Medicina do ABC - CEPHO	Santo Andre	SAO Paulo	Brazil	09060-650
11	Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral	Itajai	SC	Brazil	88.301-220
12	Fundacao do ABC-Faculdade de Medicina do ABC	Santo Andre	SP	Brazil	09060-870
13	Hospital AC Camargo_Fundacao Antonio Prudente	Sao Paulo	SP	Brazil	01509-900
14	Centro de Pesquisa Clinica do IBCC - Instituto Brasileiro de Controle do Cancer	Sao Paulo	SP	Brazil	03102-006
15	Hospital AC Camargo_Fundacao Antonio Prudente	Sao Paulo		Brazil	01509-900
16	James Lind Centro de lnvestigacion del Cancer	Araucania		Chile	4800827
17	The First Affiliated Hospital of Anhui Medical University, Department of Medical Oncology	Hefei	Anhui	China	230022
18	The Fifth Medical Center of PLA General Hospital	Beijing	Beijing	China	100071
19	Daping Hospital, Research Institute of Surgery Third Military Medical University	Chongqing	Chongqing	China	400042
20	Harbin Medical University Cancer Hospital/Oncology Department	Harbin	Heilongjiang	China	150081
21	Henan Cancer Hospital/Respiration internal medicine	Zhengzhou	Henan	China	450008
22	Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology/Cancer Center	Wuhan	Hubei	China	430030
23	Hubei Cancer Hospital	Wuhan	Hubei	China	430079
24	Shanghai Sixth People's Hospital	Shanghai	Shanghai	China	200233
25	Oncology Department, West China Hospital of Sichuan University	Chengdu	Sichuan	China	610041
26	Zhejiang Cancer Hospital	Hangzhou	Zhejiang	China	310022
27	Tianjin Cancer Hospital	Tianjin		China	300060
28	Urocentrum Plzen Research Site s.r.o.	Plzen		Czechia	30100
29	Vseobecna fakultni nemocnice v Praze, Fakultni poliklinika, Centrum pro lecbu bolesti	Praha 2		Czechia	128 00
30	Veszprem Megyei Tudogyogyintezet Farkasgyepu	Farkasgyepu		Hungary	8582
31	CRU Hungary Ltd., MISEK Hematology Department-CRU Co.	Miskolc		Hungary	3529
32	CRU Hungary Ltd., MISEK-CRU	Miskolc		Hungary	3529
33	Josa Andras Hospital, Clinical Research Department	Nyiregyhaza		Hungary	4400
34	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz	Nyiregyhaza		Hungary	4400
35	Help-MR Diagnosztika Kft.	Szekesfehervar		Hungary	8000
36	HaEmek Medical Center	Afula		Israel	1834111
37	Rambam Health Care Campus	Haifa		Israel	3109601
38	Chaim Sheba Medical Center	Ramat Gan		Israel	52621
39	National Hospital Organization Toyohashi Medical Center	Toyohashi	Aichi	Japan	440-8510
40	National Cancer Center Hospital East	Kashiwa	Chiba	Japan	277-8577
41	Gunma Prefectural Cancer Center	Ota	Gunma	Japan	373-8550
42	Nishinomiya Municipal Central Hospital	Nishinomiya	Hyogo	Japan	663-8014
43	The Hospital of Hyogo College of Medicine	Nishinomiya	Hyogo	Japan	663-8501
44	Saga-Ken Medical Centre Koseikan	Saga		Japan	840-8571
45	National Hospital Organization Tokyo Medical Center	Tokyo		Japan	152-8902
46	Clinical Trial Pharmacy, National Cancer Center	Goyang-si	Gyeonggi-do	Korea, Republic of	10408
47	Imaging Facilities, National Cancer Center	Goyang-si	Gyeonggi-do	Korea, Republic of	10408
48	National Cancer Center	Goyang-si	Gyeonggi-do	Korea, Republic of	10408
49	Keimyung University Dongsan Medical Center	Daegu		Korea, Republic of	42601
50	Clinical Trial Pharmacy, Severance Hospital	Seoul		Korea, Republic of	03722
51	Imaging Facilities, Severance Hospital	Seoul		Korea, Republic of	03722
52	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
53	Samsung Medical Center	Seoul		Korea, Republic of	06351
54	Powiatowy Zespol Zakladow Opieki Zdrowotnej Oddzial Opieki Paliatywnej	Bedzin		Poland	42-500
55	NZOZ Vitamed im. Edyty Jakubow	Bialystok		Poland	15-215
56	Poradnia Otropedyczno-Urazowa; Gabient RTG	Bialystok		Poland	15-437
57	Pracownia RTG Helimed	Czeladz		Poland	41-250
58	Niepubliczny Zaklad Opieki Zdrowotnej, Zespol Medyczno-Opiekunczy Alicja Kluczna	Dabrowa Gornicza		Poland	41-300
59	Hospicjum im. Ks. Eugeniusza Dutkiewicza SAC w Gdansku	Gdansk		Poland	80-208
60	Stowarzyszenie Przyjaciol Chorych Hospicjum w Gliwicach NZOZ Hospicjum Milosierdzia Bozego	Gliwice		Poland	44-100
61	Stowarzyszenie Przyjaciol Chorych Hospicjum w Gliwicach, NZOZ Hospicjum Milosierdzia Bozego	Gliwice		Poland	44-100
62	Regionalny Szpital Specjalistyczny im. Dr. Wl.Bieganskiego, Oddzial Onkologii Klinicznej	Grudziadz		Poland	86-300
63	SCANiX Sp.z o.o	Katowice		Poland	40-057
64	NZOZ "Vegamed"	Katowice		Poland	40-060
65	Helimed Diagnostic Imaging Sp. z o.o., Sp. komandytowa	Katowice		Poland	40-760
66	Helimed Diagnostic Imaging Sp. z.o.o., Sp. komandytowa	Katowice		Poland	40-760
67	Centrum Diagnostyki Obrazowej EPIONE	Katowice		Poland	40-872
68	NZOZ Neuromed M. i M. Nastaj Sp. P.	Lublin		Poland	20-064
69	SK Przemienienia Panskiego UM im. Karola Marcinkowskiego w Poznaniu,	Poznan		Poland	61-245
70	Klinika Nowotworow Piersi i Chirurgii Rekonstrukcyjnej w Centrum Onkologii -Instytucie	Warszawa		Poland	02-781
71	Szpital LUX MED	Warszawa		Poland	02-801
72	SC Oncolab SRL	Craiova	Dolj	Romania	200385
73	S.C. Oncocenter Oncologie Clinica S.R.L.	Timisoara	Timis	Romania	300166
74	Spitalul Clinic C.F. 2 Bucuresti. Departament Oncologie, Sectia Medicala 2	Bucuresti		Romania	011464
75	Národný onkologický ústav	Bratislava		Slovakia	833 10
76	DEMOMED s.r.o.	Nove Zamky		Slovakia	94001
77	MUDr. Viliam Cibik, PhD, s.r.o.	Pruske		Slovakia	018 52
78	Fakultna Nemocnica S Poliklinikou Zilina	Zilina		Slovakia	012 07
79	Hospital General Universitario de Elche Servicio de Farmacia	Elche	Alicante	Spain	03203
80	Hospital General Universitario de Elche	Elche	Alicante	Spain	03203
81	Hospital Can Misses	Ibiza	Islas Baleares	Spain	07800
82	Hospital General Universitario de Alicante	Alicante		Spain	03010
83	Hospital Universitario de la Princesa	Madrid		Spain	28006
84	Hospital La Moraleja	Madrid		Spain	28050
85	Hospital Universitario HM Sanchinarro	Madrid		Spain	28050
86	St George's University Hospitals NHS Foundation Trust	Tooting	London	United Kingdom	SW17 0QT
87	NHS Lothian, Royal Infirmary of Edinburgh	Edinburgh	Scotland	United Kingdom	EH16 4SA
88	NHS Lothian, Western General Hospital	Edinburgh	Scotland	United Kingdom	EH4 2XU
89	NHS Lothian	Edinburgh	Scotland	United Kingdom	EH4 2XU