ROMIPLOSTIM for Chemotherapy-induced thrombocytopenia | Non-small cell lung cancer | Ovarian cancer | Breast cancer

Inclusion criteria

• {"criterion_text":"- 1. 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."}
• {"criterion_text":"- 2. Males or females greater than or equal to 18 years of age at signing of the informed consent."}
• {"criterion_text":"- 3. 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."}
• {"criterion_text":"- 4. 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."}
• {"criterion_text":"- 5. Subjects must have a local platelet count ≤ 85 x 109/L on day 1 of the study."}
• {"criterion_text":"- 6. 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."}
• {"criterion_text":"- 7. Subjects must have at least 3 remaining planned cycles of chemotherapy at study enrollment."}
• {"criterion_text":"- 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2."}

Exclusion criteria

• {"criterion_text":"- 1. Acute lymphoblastic leukemia"}
• {"criterion_text":"- 9. 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."}
• {"criterion_text":"- 11. Evidence of active infection within 2 weeks prior to the first dose of study treatment."}
• {"criterion_text":"- 12. 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."}
• {"criterion_text":"- 13. 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: •\tPositive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B). •\tNegative 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. •\tPositive hepatitis C virus antibody: hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C."}
• {"criterion_text":"- 14. In addition to the conditions listed in exclusion criteria 201 through 206, secondary malignancy within the past 5 years except: o\tAdequately treated non-melanoma skin cancer or lentigo maligna without o\tevidence of disease. o\tAdequately treated cervical carcinoma in situ without evidence of disease. o\tAdequately treated breast ductal carcinoma in situ without evidence of o\tdisease. o\tProstatic intraepithelial neoplasia without evidence of prostate cancer. o\tAdequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ. o\tMalignancy 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 (excluding malignancies listed in exclusion criteria 201 – 206)."}
• {"criterion_text":"- 15. Thrombocytopenia due to another etiology other than CIT (eg, chronic liver disease, prior history of immune thrombocytopenia purpura)."}
• {"criterion_text":"- 16. 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 the 3 planned on-study cycles of chemotherapy."}
• {"criterion_text":"- 17. 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. 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."}
• {"criterion_text":"- 18. 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.)"}
• {"criterion_text":"- 19. 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."}
• {"criterion_text":"- 10. History of arterial thrombotic events (eg, myocardial ischemia, transient ischemic attack, or stroke) within 6 months prior to screening."}
• {"criterion_text":"- 20. 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."}
• {"criterion_text":"- 21. Subject has known sensitivity to any of the products to be administered during dosing."}
• {"criterion_text":"- 22. 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."}
• {"criterion_text":"- 23. 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."}
• {"criterion_text":"- 24. 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."}
• {"criterion_text":"- 25. Male subjects unwilling to abstain from donating sperm during treatment (and chemotherapy) and for an additional 7 months after treatment (and chemotherapy) discontinuation."}
• {"criterion_text":"- 2. Acute myeloid leukemia."}
• {"criterion_text":"- 3. Any myeloid malignancy."}
• {"criterion_text":"- 4. 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."}
• {"criterion_text":"- 5. Myeloproliferative disease."}
• {"criterion_text":"- 6. Multiple myeloma."}
• {"criterion_text":"- 7. 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."}
• {"criterion_text":"- 8. Major surgery less than or equal to 28 days or minor surgery less than or equal to 3 days prior to enrollment."}

Primary endpoints

• {"endpoint_text":"- 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 Time Frame: 48 days","definition_or_measurement_approach":"Defined as the incidence of chemotherapy dose delay or reduction due to thrombocytopenia during the second and third cycles of the planned on-study chemotherapy regimen. Thrombocytopenia-induced modifications include dose reduction, delay, omission, or discontinuation due to platelet counts < 100 x 10^9/L. Time frame: 48 days."}

Secondary endpoints

• {"endpoint_text":"- 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 Time Frame: 48 days","definition_or_measurement_approach":"Depth of platelet count nadir measured from start of first on-study chemotherapy cycle through end of treatment period. Time Frame: 48 days."}
• {"endpoint_text":"- 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. Time Frame: 7 days","definition_or_measurement_approach":"Time from baseline to first platelet response defined as platelet count ≥100 x 10^9/L without platelet transfusion in prior 7 days. Time Frame: 7 days."}
• {"endpoint_text":"- 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. Time Frame: 48 days","definition_or_measurement_approach":"Duration-adjusted event rate of bleeding events of CTCAE grade ≥2 assessed using CTCAE v5.0. Time Frame: 48 days."}
• {"endpoint_text":"- Overall survival 1-year overall survival Time Frame: 1 year","definition_or_measurement_approach":"Overall survival measured at 1 year (time from randomization to death from any cause). Time Frame: 1 year."}
• {"endpoint_text":"- Proportion of subjects with at least 1 incidence of platelet transfusion platelet transfusion(s) during the treatment period Time Frame: 48 days","definition_or_measurement_approach":"Proportion of subjects receiving ≥1 platelet transfusion during the treatment period. Time Frame: 48 days."}
• {"endpoint_text":"- 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 Time Frame: 7 days","definition_or_measurement_approach":"Proportion achieving platelet count ≥100 x 10^9/L at any time up to week 4 (i.e., 7 days after third scheduled IP dose) without platelet transfusion in preceding 7 days. Time Frame: 7 days."}
• {"endpoint_text":"- 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. Time Frame: 36 months","definition_or_measurement_approach":"Incidence of treatment-emergent adverse events, fatal AEs, serious AEs, or clinically significant lab changes recorded through end of study, up to 36 months. Time Frame: 36 months."}
• {"endpoint_text":"- Number of subjects who develop anti-romiplostim antibodies Through end of study up to 36 months Time Frame: 36 months","definition_or_measurement_approach":"Number of subjects who develop anti-romiplostim antibodies assessed up to 36 months. Time Frame: 36 months."}
• {"endpoint_text":"- Number of subjects who develop anti-TPO antibodies Through end of study, up to 36 months Time Frame: 36 months","definition_or_measurement_approach":"Number of subjects who develop anti-TPO antibodies assessed up to 36 months. Time Frame: 36 months."}
• {"endpoint_text":"- Number of subjects who experience myelodysplastic syndromes Through end of study, up to 36 months Time Frame: 36 months","definition_or_measurement_approach":"Number of subjects who experience myelodysplastic syndromes assessed up to 36 months. Time Frame: 36 months."}
• {"endpoint_text":"- Number of subjects who experience secondary malignancies Through end of study, up to 36 months Time Frame: 36 months","definition_or_measurement_approach":"Number of subjects who experience secondary malignancies assessed up to 36 months. Time Frame: 36 months."}

Methods

• Investigator site referral via participating hospital oncology departments across member states (site-to-patient recruitment).
• Doctor-to-doctor recruitment letters/materials (K2 Doctor to Doctor Letter documents listed).
• Patient-facing materials including patient flyers and visit guides (K2 Patient Flyer, Patient Visit Guide documents listed) distributed at sites.
• Pre-screening and anonymized pre-screening information collection via an online tool provided/managed by Reify Health Inc. (collection of anonymized pre-screening information from Investigator sites via an online tool).
• Commercial recruitment/support vendors involved in production/supply of study and recruitment material (Clariness GmbH: Study and Recruitment Material).

Greece

Earliest CTIS Part Ii Submission Date

03-06-2024

Latest Decision Or Authorization Date

01-04-2025

Processing Time Days

302

Number Of Sites

6

Number Of Participants

13

Portugal

Earliest CTIS Part Ii Submission Date

18-04-2024

Latest Decision Or Authorization Date

17-12-2024

Processing Time Days

243

Number Of Sites

1

Number Of Participants

1

Poland

Earliest CTIS Part Ii Submission Date

29-04-2024

Latest Decision Or Authorization Date

25-06-2025

Processing Time Days

422

Number Of Sites

10

Number Of Participants

3

Spain

Earliest CTIS Part Ii Submission Date

17-04-2024

Latest Decision Or Authorization Date

05-03-2026

Processing Time Days

687

Number Of Sites

7

Number Of Participants

11

Romania

Earliest CTIS Part Ii Submission Date

22-04-2024

Latest Decision Or Authorization Date

04-05-2026

Processing Time Days

742

Number Of Sites

9

Number Of Participants

18

Primary sponsor

Full Name

Amgen Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Bioclinica Inc.

Responsibilities

Adjudication of study endpoints

Name

PPD Development LP

Responsibilities

ADA Antibody sampling

Name

Almac Clinical Technologies LLC

Name

Q Squared Solutions Limited

Name

Reify Health Inc.

Responsibilities

Collection of anonymized pre-screening information from Investigator sites via an online tool.

Third parties

• {"country":"Germany","full_name":"Clariness GmbH","duties_or_roles":"Study and Recruitment Material","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Medical Equipment Supplies And Management Limited","duties_or_roles":"Study equipment supply","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Adjudication of study endpoints","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Reify Health Inc.","duties_or_roles":"Collection of anonymized pre-screening information from Investigator sites via an online tool.","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"China","full_name":"Wuxi Apptec Co. Ltd.","duties_or_roles":"PK Sampling","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"ADA Antibody sampling","organisation_type":"Pharmaceutical company"}