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

Chemotherapy-induced Thrombocytopenia Clinical Trial

— RECITE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03362177
• Other study ID #: 20140346
• Secondary ID: 2017-002992-25
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 30, 2019
• Est. completion date: January 24, 2025

Study information

• Verified date: February 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 162
• Est. completion date: January 24, 2025
• Est. primary completion date: January 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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?/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 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 109/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 3X ULN; alanine aminotransferase [ALT] or aspartate aminotransferase [AST] 3X ULN for subjects without liver metastases or 5X 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.

Related Conditions & MeSH terms

• Chemotherapy-induced Thrombocytopenia
• Colorectal Neoplasms
• Thrombocytopenia

Intervention

Biological:
• Romiplostim
This study is designed to study Romiplostim for the treatment of chemotherapy-induced thrombocytopenia (CIT) in patients receiving chemotherapy for the treatment of gastrointestinal/colorectal/pancreatic cancer.

Other:
• Placebo
Placebo Comparator

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Brazil,  Bulgaria,  Canada,  Colombia,  France,  Greece,  Hungary,  Italy,  Mexico,  Peru,  Poland,  Portugal,  Romania,  Russian Federation,  Spain,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of a Thrombocytopenia-induced chemotherapy dose modification during the second or third on study chemotherapy cycles.	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	48 days
Secondary	Depth of Platelet Count	the depth of the platelet count nadir from the start of the first on-study chemotherapy cycle through the end of the treatment period	48 days
Secondary	First platelet response	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	7 Days
Secondary	Bleeding Events	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	48 days
Secondary	Overall Survival	1-year overall survival	1-year
Secondary	Subject incidence of Platelet Transfusion	platelet transfusion(s) during the treatment period	48 days
Secondary	Platelet Count	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	7 days
Secondary	AEs/SAEs overall safety of romiplostim	Through end of study, up to 36 months	36 months

External Links

•   AmgenTrials clinical trials website