Study of Romiplostim for Chemotherapy-induced Thrombocytopenia in Adult Subjects With Non-small Cell Lung Cancer (NSCLC), Ovarian Cancer, or Breast Cancer

Chemotherapy-induced Thrombocytopenia Clinical Trial

Official title:

PROCLAIM: A Phase 3 Randomized Placebo-controlled Double-blind Study of Romiplostim for the Treatment of Chemotherapy-induced Thrombocytopenia in Patients Receiving Chemotherapy for Treatment of Non-small Cell Lung Cancer (NSCLC), Ovarian Cancer, or Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03937154
• Other study ID #: 20170770
• Status: Recruiting
• Phase: Phase 3
• Start date: February 26, 2020
• Est. completion date: February 13, 2027

Study information

• Verified date: May 2024
• Source: Amgen
• Contact: Amgen Call Center
• Phone: 866-572-6436
• Email: medinfo[@]amgen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the efficacy of romiplostim for the treatment of CIT in patients receiving chemotherapy for the treatment of NSCLC, ovarian cancer, or breast cancer measured by the ability to administer on-time, full-dose chemotherapy

Description:

This is a phase 3, randomized, placebo-controlled, multicenter, international study for the treatment of CIT in adult subjects receiving chemotherapy for the treatment of NSCLC, ovarian cancer, or breast cancer. Subjects must have a platelet count ≤ 85 x 10^9/L on day 1 of the study. The study will consist of a screening period of up to 4 weeks, a treatment period long enough to allow for assessment of 3 planned cycles of chemotherapy, a follow-up visit, and long-term follow-up (LTFU). Given that subjects are required to have 3 remaining planned cycles of chemotherapy, the chemotherapy cycles may be 3 or 4 weeks in duration, and the investigational product dose adjustment guidelines allow for up to 12 weeks of dosing before a subject is declared a non-responder, the majority of study subjects will receive investigational product for a range of 10-24 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 162
• Est. completion date: February 13, 2027
• Est. primary completion date: February 13, 2026
• 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.
• Documented active stage I, II, III or IV locally advanced or metastatic of the following tumor types: NSCLC, breast cancer, or ovarian cancer (includes fallopian tube epithelial carcinomas and peritoneal epithelial carcinoma of unknown primary), or any stage recurrent disease. Patients with documented locally advanced (stage III) NSCLC should not be amenable to definitive treatment with chemoradiation and/or surgery.
• Subjects must be receiving cancer treatment with 21- or 28-day cycles, using one of the following carboplatinum-based combination chemotherapy regimens: carboplatin/gemcitabine based, carboplatin/pemetrexed based, carboplatin/liposomal doxorubicin based or carboplatin/taxane based (which includes either paclitaxel, nab-paclitaxel, or docetaxel) or single agent chemotherapy regimen with any of the above mentioned drugs. Use of combination regimens with one of the above carboplatinum-based regimens is permitted with (1) anti-angiogenic agents (such as bevacizumab); (2) targeted therapy (such as anti-epidermal growth factor agents or anti- human epidermal growth factor receptor 2) or (3) immune checkpoint inhibitors. Cycle duration is based on intervals between day 1 of chemotherapy cycles (overlapping with carboplatin intervals) every 21 or 28 day cycles for single agent regimens. OR, Subjects must have CIT from a non-protocol chemotherapy regimen, planning to start treatment with one of the above protocol chemotherapy regimens which has been delayed = 1 week due to CIT.
• Subjects must have a local platelet count = 85 x 109/L on day 1 of the study.
• Subjects must be at least 21 or 28 days removed from the start of the chemotherapy cycle immediately prior to study day 1 if receiving a 21-day or 28-day cycle chemotherapy regimen, respectively.
• 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:

• 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 greater than 470 msec, pericardial disease, or myocardial infarction.
• Major surgery less than or equal to 28 days or minor surgery less than or equal to 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 stable and suitable for continued therapeutic anticoagulation during trial participation.
• History of arterial thrombotic events (eg, myocardial ischemia, transient ischemic attack, or stroke) within 6 months prior to screening.
• Evidence of active infection within 2 weeks prior to the first dose of study treatment.
• Known human immunodeficiency virus infection with any detectable viral load at screening. 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 of chronic hepatitis C or hepatitis B 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: hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C.
• In addition to the conditions listed in exclusion criteria 201 through 206, 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 greater than or equal to 3 years before enrollment and felt to be at low risk for recurrence by the treating physician (excluding malignancies listed in exclusion criteria 201 - 206).
• Thrombocytopenia due to another etiology other than CIT (eg, chronic liver disease, prior history of immune thrombocytopenia purpura).
• Any combined modality regimen containing radiation therapy or surgery occurring concomitantly with neo-adjuvant chemotherapy or where radiation therapy is planned during the cycle preceding 3 planned on-study cycles of chemotherapy.

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 (or plan to receive) 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 less than 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 less than 30 mL/min using the Cockcroft-Gault estimated creatinine clearance as assessed by local laboratory. If local laboratory results are not available use central laboratory results. during screening.
• Abnormal liver function (total bilirubin greater than 3X ULN; alanine aminotransferase [ALT] or aspartate aminotransferase [AST] greater than 3X ULN for subjects without liver metastases or greater than or equal to 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 7 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 7 months after treatment (and chemotherapy) discontinuation. Refer to Appendix 5 for additional contraceptive information.
• 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 7 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 7 months after treatment (and chemotherapy) discontinuation.
• Male subjects unwilling to abstain from donating sperm during treatment (and chemotherapy) and for an additional 7 months after treatment (and chemotherapy) discontinuation.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Ovarian Epithelial
• Chemotherapy-induced Thrombocytopenia
• Lung Neoplasms
• Ovarian Neoplasms
• Thrombocytopenia

Intervention

Drug:
• Romiplostim
This study is designed to study Romiplostim for the treatment of chemotherapy-induced thrombocytopenia (CIT) in patients receiving chemotherapy for the treatment of non-small cell lung cancer (NSCLC), ovarian cancer, or breast cancer
• Placebo
Placebo comparator

Locations

Country	Name	City	State
Argentina	Centro Medico Austral	Ciudad Autónoma de Buenos Aires	Distrito Federal
Argentina	Instituto Oncologico Cordoba	Ciudad de Cordoba	Córdoba
Argentina	Centro de Diagnostico Investigacion y Tratamiento	Salta
Argentina	Centro de Investigaciones Clínicas Clínica Viedma	Viedma	Río Negro
Austria	Medizinische Universitaet Innsbruck	Innsbruck
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	Curitba	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	Multiprofile Hospital for Active Treatment Serdika EOOD	Sofia
Bulgaria	Specialized Hospital for Active Treatment of Oncology EAD	Sofia
Chile	Orlandi Oncologia	Santiago
Chile	James Lind Centro de Investigacion del Cancer	Temuco	Cautín
Colombia	Centro Medico Imbanaco	Cali	Valle Del Cauca
Colombia	Oncomedica Imat	Monteria	Córdoba
Greece	Agios Savvas Anticancer Hospital	Athens
Greece	Alexandra Hospital	Athens
Greece	Attikon University Hospital	Athens
Greece	Henry Dunant Hospital Center	Athens
Greece	Sotiria General Hospital	Athens
Greece	University Hospital of Heraklion	Heraklion - Crete
Greece	Agios Loukas Clinic	Thessaloniki
Greece	Iatriko Diavalkaniko Thessalonikis	Thessaloniki
Hungary	Semmelweis Egyetem	Budapest
Hungary	Farkasgyepui Tudogyogyintezet	Farkasgyepu
Hungary	Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktatokorhaz	Gyor
Hungary	Fejer Varmegyei Szent Gyorgy Egyetemi Oktato Korhaz	Szekesfehervar
Hungary	Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz-Rendelointezet	Szolnok
Hungary	Reformatus Pulmonologiai Centrum	Torokbalint
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	Powiatowe Centrum Zdrowia w Brzezinach Sp Z o o	Brzeziny
Poland	Centrum Onkologii im prof Franciszka Lukaszczyka w Bydgoszczy	Bydgoszcz
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu	Poznan
Poland	Wojewodzki Szpital im Sw Ojca Pio w Przemyslu	Przemysl
Portugal	Unidade Local de Saude de Santa Maria, EPE - Hospital Pulido Valente	Lisboa
Portugal	Unidade Local de Saude de Matosinhos, EPE - Hospital Pedro Hispano	Matosinhos
Portugal	Unidade Local de Saude de Santo Antonio, EPE - Hospital de Santo Antonio	Porto
Portugal	Unidade Local de Saude de Sao Joao, EPE - Hospital de Sao Joao	Porto
Romania	Institutul Oncologic, Prof Dr Alexandru Trestioreanu	Bucharest
Romania	Institutul Oncologic, Prof Dr Alexandru Trestioreanu	Bucharest
Romania	Spitalul Clinic Coltea	Bucharest
Romania	Spitalul Universitar de Urgenta Elias	Bucharest
Romania	Institutul Oncologic Prof Dr Ion Chiricuta Cluj-Napoca	Cluj Napoca
Romania	SC Medisprof SRL	Cluj-Napoca
Romania	Institutul Regional de Oncologie Iasi	Iasi
Romania	Spitalul Municipal Ploiesti	Ploiesti
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	State Healthcare Institution Goroda Moskvi City Clinical Hospital 1	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	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	Instituto Oncologico IOB	Barcelona	Cataluña
Spain	Consorcio Hospitalario Provincial de Castellon	Castellon	Comunidad Valenciana
Spain	Hospital Universitario de Fuenlabrada	Fuenlabrada	Madrid
Spain	Hospital Clinico Universitario San Cecilio	Granada	Andalucía
Spain	Hospital Universitario Madrid Sanchinarro	Madrid
Spain	Hospital Santa Maria Nai	Ourense	Galicia
Spain	Hospital Clinico Universitario de Salamanca	Salamanca	Castilla León
Spain	Hospital Universitario Nuestra Señora de Valme	Sevilla	Andalucía
Spain	Hospital Universitario Virgen del Rocio	Sevilla	Andalucía
Turkey	Ankara Bilkent Sehir Hastanesi	Ankara
Turkey	Doktor Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi	Ankara
Turkey	Doktor Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi	Ankara
Turkey	Memorial Ankara Hastanesi	Ankara
Turkey	Saglik Bilimleri Universitesi Gulhane Egitim ve Arastirma Hastanesi	Ankara
Turkey	Saglik Bilimleri University Ankara Ataturk Chest Diseases and Chest Surgery Training and Research Ho	Ankara
Turkey	Pamukkale Universitesi Tip Fakultesi Hastanesi	Denizli
Turkey	Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi	Edirne
Turkey	Istanbul Universitesi Cerrahpasa Tip Fakultesi	Istanbul
Turkey	Marmara Universitesi Tip Fakultesi Hastanesi	Istanbul
Turkey	Izmir Ataturk Egitim ve Arastirma Hastanesi	Izmir
Turkey	Izmir Ekonomi Universitesi Medical Point Hastanesi	Izmir
Turkey	Kocaeli Universitesi Tip Fakultesi Hastanesi	Kocaeli
Turkey	Necmettin Erbakan Universitesi Tip Fakultesi Hastanesi	Konya
Turkey	Inonu Universitesi Turgut Ozal Tip Merkezi	Malatya
Turkey	Namik Kemal Universitesi Hastanesi	Tekirdag
Ukraine	Communal Institution Chernivtsi Regional Clinical Oncological Dispensary	Chernivtsi
Ukraine	Transcarpathian Regional Clinical Oncological Dispensary	Uzhgorod
Ukraine	Vinnytsya Regional Clinical Oncological Dispensary	Vinnytsya
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	Saint Lukes University Health Network	Bethlehem	Pennsylvania
United States	Broome Oncology LLC	Binghamton	New York
United States	Saint Alphonsus Regional Medical Center	Boise	Idaho
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	Great Falls Clinic	Great Falls	Montana
United States	Hattiesburg Clinic Hematology/Oncology	Hattiesburg	Mississippi
United States	Saint Bernards Medical Center	Jonesboro	Arkansas
United States	University of Miami School of Medicine	Miami	Florida
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Ocala Oncology Center	Ocala	Florida
United States	Community Cancer Trials of Utah	Ogden	Utah
United States	Nebraska Cancer Specialists	Omaha	Nebraska
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	Yakima Valley Memorial Hospital	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of either a chemotherapy dose delay or reduction	No thrombocytopenia-induced modification of any myelosuppressive 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 109/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	Time to 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	the duration-adjusted event rate of = grade 2 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	Proportion of subjects with at leat 1 incidence of platelet transfusion	platelet transfusion(s) during the treatment period	48 days
Secondary	proportion of patients achieving platelet count >= 100 x 10 9/L	7 days after 3rd dose of IP with no transfusions in preceding 7 days	7 days
Secondary	The subject incidence of adverse events	Through end of study, up to 36 months. It will be counted in as an adverse event: any treatment - emergent adverse events, fatal adverse events, serious adverse events, or clinically significant changes in laboratory values.	36 months
Secondary	Number of subjects who develop anti-romiplostim antibodies	Through end of study up to 36 months	36 Months
Secondary	Number of subjects who develop anti-TPO antibodies	Through end of study, up to 36 months	36 months
Secondary	Number of subjects who experience myelodysplastic syndromes	Through end of study, up to 36 months	36 months
Secondary	Number of subjects who experience secondary malignancies	Through end of study, up to 36 months	36 months

External Links

•   AmgenTrials clinical trials website