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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT03937154

Studienbeginn:
Februar 2020

Letztes Update:
22.12.2020

Wirkstoff:
Romiplostim, Placebo

Indikation (Clinical Trials):
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Ovarian Neoplasms, Carcinoma, Ovarian Epithelial, Thrombocytopenia

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Amgen

Collaborator:
-

Studienleiter

MD
Study Director
Amgen

Kontakt

Studienlocations (3 von 80)

Research Site
C1019ABS Ciudad Autónoma de Buenos Aires
ArgentinaRekrutierend» Google-Maps
Research Site
163045 Arkhangelsk
Russian FederationRekrutierend» Google-Maps
Research Site
143442 Moscow Region
Russian FederationRekrutierend» Google-Maps
Research Site
603089 Nizhniy Novgorod
Russian FederationRekrutierend» Google-Maps
Research Site
357502 Pyatigorsk
Russian FederationRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed 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 < 75 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 10-22 weeks.

Ein-/Ausschlusskriterien

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 NSCLC, breast

cancer, or ovarian cancer, 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). 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 days.

- Subjects must have a platelet count less than 75 x 10 9/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. Subjects without a documented diagnosis

in their medical history will require a central. laboratory assessment at screening.

- Known active of chronic hepatitis C or hepatitis B infection. Subjects without a

documented diagnosis in their medical history will require a central laboratory

assessment at screening. 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

before the planned 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 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 less than 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 central laboratory

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 central laboratory during screening.

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.

Studien-Rationale

Primary outcome:

1. Incidence of either a chemotherapy dose delay or reduction (Time Frame - 48 days):
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



Secondary outcome:

1. Depth of Platelet Count (Time Frame - 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

2. Time to First platelet response (Time Frame - 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

3. the duration-adjusted event rate of ≥ grade 2 bleeding events (Time Frame - 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

4. Overall survival (Time Frame - 1 Year):
1-year overall survival

5. Proportion of subjects with at leat 1 incidence of platelet transfusion (Time Frame - 48 days):
platelet transfusion(s) during the treatment period

6. proportion of patients achieving platelet count >= 100 x 10 9/L (Time Frame - 7 days):
7 days after 3rd dose of IP with no transfusions in preceding 7 days

7. The subject incidence of adverse events (Time Frame - 36 months):
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.

8. Number of subjects who develop anti-romiplostim antibodies (Time Frame - 36 Months):
Through end of study up to 36 months

9. Number of subjects who develop anti-TPO antibodies (Time Frame - 36 months):
Through end of study, up to 36 months

10. Number of subjects who experience myelodysplastic syndromes (Time Frame - 36 months):
Through end of study, up to 36 months

11. Number of subjects who experience secondary malignancies (Time Frame - 36 months):
Through end of study, up to 36 months

Studien-Arme

  • Experimental: Romiplostim
    The study in a 2:1 randomization ratio(108 subjects to romiplostim). Amgen investigational product (romiplostim or placebo) will be administered in the clinic by a qualified healthcare provider as a subcutaneous injection.
  • Placebo Comparator: Placebo
    The study in a 2:1 randomization ratio (54 subjects to placebo) Amgen investigational product (romiplostim or placebo) will be administered in the clinic by a qualified healthcare provider as a subcutaneous injection.

Geprüfte Regime

  • Romiplostim (Nplate):
    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

Quelle: ClinicalTrials.gov


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