Clinical trial NCT03362177: Study of Romiplostim for Chemotherapy-induced Thrombocytopenia in Adult Subjects With Gastrointestinal, Pancreatic, or Colorectal Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chemotherapy-induced Thrombocytopenia
Keywords: Chemotherapy Induced Thrombocytopenia
Gastrointestinal Cancer
Colorectal Cancer
Pancreatic Cancer
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2017-12-05
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of a Thrombocytopenia-induced chemotherapy dose modification during the second or third on study chemotherapy cycles.
timeFrame: 48 days
Secondary outcomes:
measure: Depth of Platelet Count
timeFrame: 48 days
measure: First platelet response
timeFrame: 7 Days
measure: Bleeding Events
timeFrame: 48 days
measure: Overall Survival
timeFrame: 1-year
measure: Subject incidence of Platelet Transfusion
timeFrame: 48 days
measure: Platelet Count
timeFrame: 7 days
measure: AEs/SAEs overall safety of romiplostim
timeFrame: 36 months
Other outcomes:
Locations:
city: Jonesboro
country: United States
facility: Saint Bernards Medical Center
state: Arkansas
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center Inc
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Grand Junction
country: United States
facility: Colorado West Healthcare System dba Grand Valley Oncology
state: Colorado
city: Orange City
country: United States
facility: Mid Florida Hematology and Oncology Centers PA
state: Florida
city: Tamarac
country: United States
facility: Oncology and Hematology Associates of West Broward, PA
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Skokie
country: United States
facility: Orchard Healthcare Research Inc
state: Illinois
city: Alexandria
country: United States
facility: Christus Saint Frances Cabrini Hospital
state: Louisiana
city: New Orleans
country: United States
facility: University Medical Center New Orleans
state: Louisiana
city: Shreveport
country: United States
facility: Christus Highland Cancer Treatment Center
state: Louisiana
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Bethesda
country: United States
facility: American Oncology Partners, PA
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic Hematology/Oncology
state: Mississippi
city: Springfield
country: United States
facility: Oncology Hematology Associates
state: Missouri
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Sparta
country: United States
facility: Regional Cancer Care Associates
state: New Jersey
city: Fort Worth
country: United States
facility: The Center for Cancer and Blood Disorders
state: Texas
city: Spokane
country: United States
facility: Medical Oncology Associates PS
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital
state: Washington
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Universitario Fundacion Favaloro
state: Buenos Aires
city: Cordoba
country: Argentina
facility: Instituto Oncologico Cordoba
state: Córdoba
city: Viedma
country: Argentina
facility: Centro de Investigaciones Clínicas Clínica Viedma
state: Río Negro
city: Salta
country: Argentina
facility: Centro de Diagnostico Investigacion y Tratamiento
city: Steyr
country: Austria
facility: Landeskrankenhaus Steyr
city: Wien
country: Austria
facility: Universitaetsklinikum Allgemeines Krankenhaus Wien
city: Curitiba
country: Brazil
facility: Instituto de Oncologia do Parana
state: Paraná
city: Teresina
country: Brazil
facility: Vencer e Oncoclinica
state: Piauí
city: Caxias do Sul
country: Brazil
facility: Centro de Pesquisa da Serra Gaucha - Cepesg
state: Rio Grande Do Sul
city: Itajaí
country: Brazil
facility: Catarina Pesquisa Clinica
state: Santa Catarina
city: Campinas
country: Brazil
facility: Loema Instituto de Pesquisa Clinica e Consultores Ltda
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Casa de Saude Santa Marcelina
state: São Paulo
city: Ruse
country: Bulgaria
facility: Complex Oncology Center - Ruse EOOD
city: Sofia
country: Bulgaria
facility: Medical Center Nadezhda Clinical EOOD
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Oncology EAD
city: Sydney
country: Canada
facility: Cape Breton Cancer Centre, Nova Scotia Health Authority
state: Nova Scotia
city: Kitchener
country: Canada
facility: Grand River Regional Cancer Centre at Grand River Hospital
state: Ontario
city: Medellin
country: Colombia
facility: Fundacion Colombiana de Cancerologia Clinica Vida
state: Antioquia
city: Monteria
country: Colombia
facility: Oncomedica Imat
state: Córdoba
city: Cali
country: Colombia
facility: Centro Medico Imbanaco
state: Valle Del Cauca
city: Brest cedex
country: France
facility: Centre Hospitalier Universitaire de Brest
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Suresnes
country: France
facility: Hopital Foch
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Athens
country: Greece
facility: General Hospital of Athens Laiko
city: Athens
country: Greece
facility: Aretaieio Hospital
city: Athens
country: Greece
facility: Evgenidio Hospital I Agia Trias
city: Athens
country: Greece
facility: Attikon University Hospital
city: Athens
country: Greece
facility: General Oncology Hospital of Kifissia Agioi Anargyroi
city: Patra
country: Greece
facility: University Hospital of Patras
city: Thessaloniki
country: Greece
facility: Agios Loukas Clinic
city: Budapest
country: Hungary
facility: Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Gyor
country: Hungary
facility: Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktatokorhaz
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar
city: Cremona
country: Italy
facility: Azienda Socio Sanitaria Territoriale di Cremona
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
city: Torino
country: Italy
facility: Azienda Ospedaliera Citta della Salute e della Scienza di Torino Ospedale Molinette
city: La Paz
country: Mexico
facility: Oncotech
state: Baja California Sur
city: San Luis Potosi
country: Mexico
facility: Centro de Atencion e Investigacion Cardiovascular del Potosi Sc
state: San Luis Potosí
city: Mexico
country: Mexico
facility: Centro Medico Nacional Siglo XXI
city: Oaxaca
country: Mexico
facility: Oaxaca Site Management Organization SC
city: Arequipa
country: Peru
facility: Hospital Goyeneche
city: Lima
country: Peru
facility: Oncosalud
city: Biala Podlaska
country: Poland
facility: Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej
city: Brzeziny
country: Poland
facility: Powiatowe Centrum Zdrowia w Brzezinach Sp Z o o
city: Poznan
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
city: Poznan
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitario de Lisboa Norte, EPE - Hospital de Santa Maria
city: Matosinhos
country: Portugal
facility: Unidade Local de Saude de Matosinhos, EPE - Hospital Pedro Hispano
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario do Porto, EPE - Hospital de Santo Antonio
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario de Sao Joao, EPE - Hospital Sao Joao
city: Vila Real
country: Portugal
facility: Centro Hospitalar Tras-os-Montes e Alto Douro EPE - Unidade de Vila Real
city: Brasov
country: Romania
facility: Policlinica de Diagnostic Rapid
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute for Digestive Disorders and Liver Transplantation
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic al Cailor Ferate Cluj Napoca
city: Cluj-Napoca
country: Romania
facility: SC Medisprof SRL
city: Craiova
country: Romania
facility: Centrul de Oncologie Sf Nectarie SRL
city: Iasi
country: Romania
facility: Institutul Regional de Oncologie Iasi
city: Timisoara
country: Romania
facility: SC Oncomed SRL
city: Arkhangelsk
country: Russian Federation
facility: SBHI of Arkhangelsk region Arkhangelsk clinical oncology dispensary
city: Kazan
country: Russian Federation
facility: Autonomic SHI Republican clinical oncology dispensary of MoH of the Republic of Tatarstan
city: Moscow Region
country: Russian Federation
facility: Medsi Group
city: Moscow
country: Russian Federation
facility: Clinical hospital 2, Group of companies medsi
city: Nizhniy Novgorod
country: Russian Federation
facility: LLC Tonus
city: Omsk
country: Russian Federation
facility: Omsk Regional Clinical Oncology Dispensary
city: Pyatigorsk
country: Russian Federation
facility: State budget institution of public health Pyatigorsk oncology dispensary
city: Ryazan
country: Russian Federation
facility: State Institution of Public Health
city: Saint Petersburg
country: Russian Federation
facility: Leningrad Regional Oncology Dispensary na L D Roman
city: Saint-Petersburg
country: Russian Federation
facility: FSBI Scientific and Research Oncology Institute named after N N Petrov
city: Sochi
country: Russian Federation
facility: State Institution of Public Health Oncology Dispensary 2 of Public Health Krasnodar Region
city: Tambov
country: Russian Federation
facility: State Institution of Public Health Tambov Regional Oncology Dispensary
city: Ufa
country: Russian Federation
facility: Respublican clinical oncology dispensary Minzdrava of Republic of Bashkortostan
city: Granada
country: Spain
facility: Hospital Clinico Universitario San Cecilio
state: Andalucía
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
state: Castilla León
city: Lleida
country: Spain
facility: Hospital Universitario Arnau de Vilanova Lleida
state: Cataluña
city: Reus
country: Spain
facility: Hospital Universitari Sant Joan de Reus
state: Cataluña
city: Ourense
country: Spain
facility: Complexo Hospitalario Universitario de Ourense
state: Galicia
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
city: Adana
country: Turkey
facility: Baskent Universitesi Adana Doktor Turgut Noyan Uygulama ve Arastirma Merkezi
city: Ankara
country: Turkey
facility: Doktor Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi
city: Ankara
country: Turkey
facility: Gazi Universitesi Saglik Arastirma ve Uygulama Merkezi Gazi Hastanesi
city: Ankara
country: Turkey
facility: Ankara Bilkent Sehir Hastanesi
city: Edirne
country: Turkey
facility: Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Onkoloji Enstitusu
city: Istanbul
country: Turkey
facility: Prof Dr Cemil Tascioglu Sehir Hastanesi
city: Istanbul
country: Turkey
facility: Goztepe Prof Dr Suleyman Yalcin Sehir Hastanesi
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi
city: Izmir
country: Turkey
facility: Izmir Ekonomi Universitesi Medical Point Hastanesi
city: Kocaeli
country: Turkey
facility: Kocaeli Universitesi Arastirma ve Uygulama Hastanesi
city: Samsun
country: Turkey
facility: VM Medical Park Samsun Hastanesi
city: Chernivtsi
country: Ukraine
facility: Communal Institution Chernivtsi Regional Clinical Oncological Dispensary
city: Ivano-Frankivsk
country: Ukraine
facility: Prykarpatskyy Clinical Oncology Centre
city: Uzhgorod
country: Ukraine
facility: Transcarpathian Regional Clinical Oncological Dispensary
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: