Study of Romiplostim for Chemotherapy-induced Thrombocytopenia in Adult Subjects With Gastrointestinal, Pancreatic, or Colorectal Cancer

Phase 3

Completed

Conditions: Chemotherapy-induced Thrombocytopenia

Interventions: Biological: Romiplostim
Other: Placebo

Registration Number: NCT03362177

Lead Sponsor: Amgen

Brief Summary: Study of Romiplostim for Chemotherapy-induced Thrombocytopenia in Adult Subjects with Gastrointestinal, Pancreatic, or Colorectal Cancer

Detailed Description: RECITE: A phase 3 Randomized Placebo-controlled Double-blind Study of Romiplostim for the Treatment of Chemotherapy-induced Thrombocytopenia in Patients Receiving Oxaliplatin-based Chemotherapy for Treatment of Gastrointestinal, Pancreatic, or Colorectal Cancer

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 165

Inclusion Criteria

Subject has provided informed consent prior to initiation of any study specific activities/procedures or subject's legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.
Males or females greater than or equal to 18 years of age at signing of the informed consent.
Histologically or cytologically confirmed diagnosis of gastrointestinal, pancreatic, or colorectal adenocarcinoma, defined as cancers of the esophagus (including esophagogastric junction [EGJ] cancer), stomach, pancreas, colon, or rectum. Tumor stage will not affect eligibility.
Subjects must be receiving 1 of the following regimens: An oxaliplatin-based chemotherapy regimen, containing 5 FU or capecitabine plus oxaliplatin (irinotecan may be added for FOLFIRINOX or FOLFOXIRI) on a 14- or 21 day schedule, respectively; OR, subjects must have chemotherapy-induced thrombocytopenia from a non-protocol chemotherapy regimen, planning to start treatment with one of the protocol chemotherapy regimens which has been delayed greater than or equal to one week due to chemotherapy-induced thrombocytopenia. Note: Use of these regimens are permitted with (1) anti angiogenic agents (such as bevacizumab) or (2) targeted therapy (such as anti epidermal growth factor receptor agents);
Subjects must have a local platelet count ≤ 85 x 10^9/L on study day 1.
Subjects must be at least 14 days removed from the start of the chemotherapy cycle immediately prior to study day 1 if they received FOLFOX, FOLFIRINOX or FOLFOXIRI, and 21 days removed if they received CAPEOX.
Subjects must have at least 3 remaining planned cycles of chemotherapy at study enrollment.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

Exclusion Criteria

Previous or Current Medical Conditions

Acute lymphoblastic leukemia.
Acute myeloid leukemia.
Any myeloid malignancy.
Myelodysplastic syndrome. Baseline bone marrow biopsy is not required to rule out MDS. However, if a bone marrow biopsy and cytogenetics were performed as part of diagnostic or staging work-up, these results will be collected to confirm.
Myeloproliferative disease.
Multiple myeloma.
Within 4 months prior to enrollment, any history of active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, clinically significant electrocardiogram (ECG) abnormalities, screening ECG with corrected QT (QTc) interval of > 470 msec, pericardial disease, or myocardial infarction.
Major surgery ≤ 28 days or minor surgery ≤ 3 days prior to enrollment.
New or uncontrolled venous thromboembolism or thrombotic events within 3 months prior to screening. To be eligible, subjects must have received at least 14 days of anticoagulation for a new thrombotic event and considered to be both stable and suitable for continued therapeutic anticoagulation during trial participation.
History of arterial thrombosis (eg, stroke or transient ischemic attack) within 6 months of screening.
Evidence of active infection within 2 weeks prior to first dose of study treatment.
Known human immunodeficiency virus infection. Subjects without a documented diagnosis in their medical history will require a local laboratory assessment at screening. If local laboratory results are not available, use central laboratory results.
Known active chronic hepatitis B or C infection. Subjects without a documented diagnosis in their medical history will require a local laboratory assessment at screening. If local laboratory results are not available, use central laboratory results. Hepatitis B and C infection is based on the following results:
Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B).
Negative HBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B.
Positive Hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C.
Secondary malignancy within the past 5 years except:
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
Adequately treated cervical carcinoma in situ without evidence of disease.
Adequately treated breast ductal carcinoma in situ without evidence of disease.
Prostatic intraepithelial neoplasia without evidence of prostate cancer.
Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.
Malignancy treated with curative intent and with no known active disease present for at least 3 years before enrollment and felt to be at low risk for recurrence by the treating physician
Thrombocytopenia due to another etiology other than CIT (eg, chronic liver disease, prior history of immune thrombocytopenia purpura).

Prior/Concomitant Therapy

• Previous use of romiplostim, pegylated recombinant human megakaryocyte growth and development factor, eltrombopag, recombinant human TPO, any other TPO receptor agonist, or any investigational platelet producing agent.

Prior/Concurrent Clinical Study Experience • Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.

Diagnostic Assessments

Anemia (hemoglobin <80 g/L [8 g/dL]) on the day of initiation of investigational product as assessed by local labs. Use of red cell transfusions and erythropoietic stimulating agents is permitted throughout the study as per institutional guidelines.
Neutropenia (absolute neutrophil count 1 x 10^9/L) on the day of initiation of investigational product as assessed by local labs. Use of granulocyte-colony stimulating factor is permitted throughout the study as per institutional guidelines.
Abnormal renal function with creatinine clearance < 30 mL/min using the Cockcroft-Gault estimated creatinine clearance as assessed by local laboratory during screening. If local laboratory results are not available, use central laboratory results.
Abnormal liver function (total bilirubin > 3 X ULN; alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 X ULN for subjects without liver metastases or ≥ 5 X ULN for subjects with liver metastases) as assessed by local laboratory during screening. If local laboratory results are not available, use central laboratory results.

Other Exclusions

Females who are pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after treatment (and chemotherapy) discontinuation (females of childbearing potential should only be included after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test.)
Females of childbearing potential unwilling to use a highly effective method of contraception during treatment and for an additional 6 months after treatment (and chemotherapy) discontinuation.
Males unwilling to use contraception* (male condom or sexual abstinence) or their female partner(s) of childbearing potential who are unwilling to use a highly effective method of contraception during treatment (and chemotherapy) and for an additional 6 months after treatment (and chemotherapy) discontinuation.

*If the male's sole partner is of non-childbearing potential, he is not required to use additional forms of contraception during the study.
Subject has known sensitivity to any of the products to be administered during dosing.
Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, COAs) to the best of the subject and investigator's knowledge.
History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment (and chemotherapy) and for an additional period of 6 months after treatment (and chemotherapy) discontinuation.
Male subjects unwilling to abstain from donating sperm during treatment (and chemotherapy) and for an additional 6 months after treatment (and chemotherapy) discontinuation.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Romiplostim	Romiplostim	Participants will be enrolled to the study in a 2:1 randomization ratio. Amgen investigational product (romiplostim or placebo) will be administered in the clinic by a qualified healthcare provider as a subcutaneous injection.
Placebo	Placebo	Participants will be enrolled to the study in a 2:1 randomization ratio. Amgen investigational product (romiplostim or placebo) will be administered in the clinic by a qualified healthcare provider as a subcutaneous injection.

Primary Outcome Measures

Name	Time	Method
Incidence of a Thrombocytopenia-induced chemotherapy dose modification during the second or third on study chemotherapy cycles.	48 days	No thrombocytopenia-induced modification of any myelosuppressive treatment agent in the second and third cycles of the planned on-study chemotherapy regimen. Thrombocytopenia-induced modifications include chemotherapy dose reduction, delay, omission, or chemotherapy treatment discontinuation due to platelet counts below 100 x 10 9/L

Secondary Outcome Measures

Name	Time	Method
Overall Survival	1-year	1-year overall survival
Depth of Platelet Count	48 days	the depth of the platelet count nadir from the start of the first on-study chemotherapy cycle through the end of the treatment period
Subject incidence of Platelet Transfusion	48 days	platelet transfusion(s) during the treatment period
First platelet response	7 Days	The time to first platelet response, defined by platelet count ≥ 100 x 109/L in the absence of platelet transfusions during the preceding 7 days
Bleeding Events	48 days	the duration-adjusted event rate of ≥ grade 2 bleeding events, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grading scale
Platelet Count	7 days	achieving a platelet count equal to or greater than 100 x 10 9/L at any time after study day 1 to week 4 (ie, 7 days after the planned third dose of investigational product) and in the absence of platelet transfusions during the preceding 7 days
AEs/SAEs overall safety of romiplostim	36 months	Through end of study, up to 36 months

Trial Locations

Locations (116): Centro Hospitalar Universitario de Sao Joao, EPE - Hospital Sao Joao
🇵🇹
Porto, Portugal
Autonomic SHI Republican clinical oncology dispensary of MoH of the Republic of Tatarstan
🇷🇺
Kazan, Russian Federation
Clinical hospital 2, Group of companies medsi
🇷🇺
Moscow, Russian Federation
State budget institution of public health Pyatigorsk oncology dispensary
🇷🇺
Pyatigorsk, Russian Federation
Omsk Regional Clinical Oncology Dispensary
🇷🇺
Omsk, Russian Federation
State Institution of Public Health
🇷🇺
Ryazan, Russian Federation
Leningrad Regional Oncology Dispensary na L D Roman
🇷🇺
Saint Petersburg, Russian Federation
FSBI Scientific and Research Oncology Institute named after N N Petrov
🇷🇺
Saint-Petersburg, Russian Federation
State Institution of Public Health Tambov Regional Oncology Dispensary
🇷🇺
Tambov, Russian Federation
State Institution of Public Health Oncology Dispensary 2 of Public Health Krasnodar Region
🇷🇺
Sochi, Russian Federation
Respublican clinical oncology dispensary Minzdrava of Republic of Bashkortostan
🇷🇺
Ufa, Russian Federation
Hospital Clinico Universitario San Cecilio
🇪🇸
Granada, Andalucía, Spain
Hospital Clinico Universitario de Salamanca
🇪🇸
Salamanca, Castilla León, Spain
Hospital Universitario Arnau de Vilanova Lleida
🇪🇸
Lleida, Cataluña, Spain
Hospital Universitari Sant Joan de Reus
🇪🇸
Reus, Cataluña, Spain
Complexo Hospitalario Universitario de Ourense
🇪🇸
Ourense, Galicia, Spain
Ankara Bilkent Sehir Hastanesi
🇹🇷
Ankara, Turkey
Gazi Universitesi Saglik Arastirma ve Uygulama Merkezi Gazi Hastanesi
🇹🇷
Ankara, Turkey
Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi
🇹🇷
Edirne, Turkey
Prof Dr Cemil Tascioglu Sehir Hastanesi
🇹🇷
Istanbul, Turkey
Kocaeli Universitesi Arastirma ve Uygulama Hastanesi
🇹🇷
Kocaeli, Turkey
Goztepe Prof Dr Suleyman Yalcin Sehir Hastanesi
🇹🇷
Istanbul, Turkey
VM Medical Park Samsun Hastanesi
🇹🇷
Samsun, Turkey
Prykarpatskyy Clinical Oncology Centre
🇺🇦
Ivano-Frankivsk, Ukraine
Hospital Universitario Madrid Sanchinarro
🇪🇸
Madrid, Spain
Medical Center Nadezhda Clinical EOOD
🇧🇬
Sofia, Bulgaria
University of California Irvine
🇺🇸
Orange, California, United States
Saint Bernards Medical Center
🇺🇸
Jonesboro, Arkansas, United States
Pacific Cancer Medical Center Inc
🇺🇸
Anaheim, California, United States
Oncology and Hematology Associates of West Broward, PA
🇺🇸
Tamarac, Florida, United States
Christus Saint Frances Cabrini Hospital
🇺🇸
Alexandria, Louisiana, United States
University Medical Center New Orleans
🇺🇸
New Orleans, Louisiana, United States
Mercy Medical Center
🇺🇸
Baltimore, Maryland, United States
American Oncology Partners, PA
🇺🇸
Bethesda, Maryland, United States
Hattiesburg Clinic Hematology/Oncology
🇺🇸
Hattiesburg, Mississippi, United States
The Center for Cancer and Blood Disorders
🇺🇸
Fort Worth, Texas, United States
Hospital Universitario Fundacion Favaloro
🇦🇷
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Instituto Oncologico Cordoba
🇦🇷
Cordoba, Córdoba, Argentina
Centro de Diagnostico Investigacion y Tratamiento
🇦🇷
Salta, Argentina
Centro de Pesquisa da Serra Gaucha - Cepesg
🇧🇷
Caxias do Sul, Rio Grande Do Sul, Brazil
Casa de Saude Santa Marcelina
🇧🇷
Sao Paulo, São Paulo, Brazil
Complex Oncology Center - Ruse EOOD
🇧🇬
Ruse, Bulgaria
Specialized Hospital for Active Treatment of Oncology EAD
🇧🇬
Sofia, Bulgaria
Cape Breton Cancer Centre, Nova Scotia Health Authority
🇨🇦
Sydney, Nova Scotia, Canada
Grand River Regional Cancer Centre at Grand River Hospital
🇨🇦
Kitchener, Ontario, Canada
Oncomedica Imat
🇨🇴
Monteria, Córdoba, Colombia
Centre Hospitalier Universitaire de Brest
🇫🇷
Brest cedex, France
Hopital Foch
🇫🇷
Suresnes, France
Institut Gustave Roussy
🇫🇷
Villejuif Cedex, France
Hôpital Européen Georges Pompidou
🇫🇷
Paris, France
General Hospital of Athens Laiko
🇬🇷
Athens, Greece
Aretaieio Hospital
🇬🇷
Athens, Greece
Evgenidio Hospital I Agia Trias
🇬🇷
Athens, Greece
Attikon University Hospital
🇬🇷
Athens, Greece
University Hospital of Patras
🇬🇷
Patra, Greece
General Oncology Hospital of Kifissia Agioi Anargyroi
🇬🇷
Athens, Greece
Agios Loukas Clinic
🇬🇷
Thessaloniki, Greece
Azienda Socio Sanitaria Territoriale di Cremona
🇮🇹
Cremona, Italy
Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej
🇵🇱
Biala Podlaska, Poland
Azienda Ospedaliera Citta della Salute e della Scienza di Torino Ospedale Molinette
🇮🇹
Torino, Italy
Oaxaca Site Management Organization SC
🇲🇽
Oaxaca, Mexico
Powiatowe Centrum Zdrowia w Brzezinach Sp Z o o
🇵🇱
Brzeziny, Poland
Centro Hospitalar Tras-os-Montes e Alto Douro EPE - Unidade de Vila Real
🇵🇹
Vila Real, Portugal
Fundeni Clinical Institute for Digestive Disorders and Liver Transplantation
🇷🇴
Bucharest, Romania
Spitalul Clinic al Cailor Ferate Cluj Napoca
🇷🇴
Cluj-Napoca, Romania
SC Medisprof SRL
🇷🇴
Cluj-Napoca, Romania
SBHI of Arkhangelsk region Arkhangelsk clinical oncology dispensary
🇷🇺
Arkhangelsk, Russian Federation
SC Oncomed SRL
🇷🇴
Timisoara, Romania
Medsi Group
🇷🇺
Moscow Region, Russian Federation
LLC Tonus
🇷🇺
Nizhniy Novgorod, Russian Federation
Baskent Universitesi Adana Doktor Turgut Noyan Uygulama ve Arastirma Merkezi
🇹🇷
Adana, Turkey
Hacettepe Universitesi Tip Fakultesi
🇹🇷
Ankara, Turkey
Doktor Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
🇹🇷
Ankara, Turkey
Istanbul Universitesi Onkoloji Enstitusu
🇹🇷
Istanbul, Turkey
Ege Universitesi Tip Fakultesi
🇹🇷
Izmir, Turkey
Izmir Ekonomi Universitesi Medical Point Hastanesi
🇹🇷
Izmir, Turkey
Communal Institution Chernivtsi Regional Clinical Oncological Dispensary
🇺🇦
Chernivtsi, Ukraine
Transcarpathian Regional Clinical Oncological Dispensary
🇺🇦
Uzhgorod, Ukraine
Debreceni Egyetem Klinikai Kozpont
🇭🇺
Debrecen, Hungary
Centro Hospitalar Universitario do Porto, EPE - Hospital de Santo Antonio
🇵🇹
Porto, Portugal
Colorado West Healthcare System dba Grand Valley Oncology
🇺🇸
Grand Junction, Colorado, United States
Mid Florida Hematology and Oncology Centers PA
🇺🇸
Orange City, Florida, United States
Cleveland Clinic Florida
🇺🇸
Weston, Florida, United States
Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Orchard Healthcare Research Inc
🇺🇸
Skokie, Illinois, United States
Christus Highland Cancer Treatment Center
🇺🇸
Shreveport, Louisiana, United States
Medical Oncology Associates PS
🇺🇸
Spokane, Washington, United States
Regional Cancer Care Associates
🇺🇸
Sparta, New Jersey, United States
Yakima Valley Memorial Hospital
🇺🇸
Yakima, Washington, United States
Instituto de Oncologia do Parana
🇧🇷
Curitiba, Paraná, Brazil
Catarina Pesquisa Clinica
🇧🇷
Itajaí, Santa Catarina, Brazil
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar
🇭🇺
Szeged, Hungary
Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet
🇭🇺
Budapest, Hungary
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
🇮🇹
Milano, Italy
Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktatokorhaz
🇭🇺
Gyor, Hungary
Uniwersytecki Szpital Kliniczny w Poznaniu
🇵🇱
Poznan, Poland
Centro de Atencion e Investigacion Cardiovascular del Potosi Sc
🇲🇽
San Luis Potosi, San Luis Potosí, Mexico
Oncology Hematology Associates
🇺🇸
Springfield, Missouri, United States
Hospital Goyeneche
🇵🇪
Arequipa, Peru
Universitaetsklinikum Allgemeines Krankenhaus Wien
🇦🇹
Wien, Austria
Centro Medico Nacional Siglo XXI
🇲🇽
Mexico, Mexico
Landeskrankenhaus Steyr
🇦🇹
Steyr, Austria
Centro de Investigaciones Clínicas Clínica Viedma
🇦🇷
Viedma, Río Negro, Argentina
Unidade Local de Saude de Matosinhos, EPE - Hospital Pedro Hispano
🇵🇹
Matosinhos, Portugal
Centrul de Oncologie Sf Nectarie SRL
🇷🇴
Craiova, Romania
Institutul Regional de Oncologie Iasi
🇷🇴
Iasi, Romania
Policlinica de Diagnostic Rapid
🇷🇴
Brasov, Romania
Fundacion Colombiana de Cancerologia Clinica Vida
🇨🇴
Medellin, Antioquia, Colombia
Oncosalud
🇵🇪
Lima, Peru
Vencer e Oncoclinica
🇧🇷
Teresina, Piauí, Brazil
Centro Medico Imbanaco
🇨🇴
Cali, Valle Del Cauca, Colombia
Centro Hospitalar Universitario de Lisboa Norte, EPE - Hospital de Santa Maria
🇵🇹
Lisboa, Portugal
Loema Instituto de Pesquisa Clinica e Consultores Ltda
🇧🇷
Campinas, São Paulo, Brazil
Oncotech
🇲🇽
La Paz, Baja California Sur, Mexico
Morristown Medical Center
🇺🇸
Morristown, New Jersey, United States