Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03362177
Recruitment Status : Recruiting
First Posted : December 5, 2017
Last Update Posted : November 19, 2020
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE October 12, 2017
First Posted Date  ICMJE December 5, 2017
Last Update Posted Date November 19, 2020
Actual Study Start Date  ICMJE September 30, 2019
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 5, 2019)
Incidence of a Thrombocytopenia-induced chemotherapy dose modification during the second or third on study chemotherapy cycles. [ Time Frame: 48 days ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: November 29, 2017)
Incidence of either a chemotherapy dose delay or reduction by [ Time Frame: 17 weeks ]
The primary endpoint is the subject incidence of either a chemotherapy dose delay by ≥ 4 days or a chemotherapy dose reduction by ≥ 15% due to thrombocytopenia in any 2 planned cycles of chemotherapy (chemotherapy cycles can be 14-, 21-, or 28-days long) during the treatment period.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2019)
  • 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
  • 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
  • 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
  • Overall Survival [ Time Frame: 1-year ]
    1-year overall survival
  • Subject incidence of Platelet Transfusion [ Time Frame: 48 days ]
    platelet transfusion(s) during the treatment period
  • Platelet Count [ Time Frame: 7 days ]
    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
  • AEs/SAEs overall safety of romiplostim [ Time Frame: 36 months ]
    Through end of study, up to 36 months
Original Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2017)
  • First platelet recovery [ Time Frame: 7 Days ]
    Secondary endpoint is the time to first platelet recovery, defined by platelet count ≥ 100 x 109/L in the absence of platelet transfusions during the preceding 7 days
  • Platelet Count [ Time Frame: 7 days ]
    7 days after 3rd dose of IP with no transfusions in preceding 7 days
  • Depth of Platelet Count [ Time Frame: 43 months ]
    3rd dose of IP through end of treatment, up to 43 months
  • Subject incidence of Platelet Transfusion [ Time Frame: up to 17 weeks ]
    Incidence of Platelet Transfusions through treatment period, up to 17 weeks
  • Bleeding Events [ Time Frame: up to 17 weeks ]
    Through treatment period, up to 17 weeks
  • AEs/SAEs [ Time Frame: up to 17 weeks ]
    Through treatment period, up to 17 weeks
  • Antibody Formation [ Time Frame: up to 17 weeks ]
    Through treatment period, up to 17 weeks
  • Vital Signs [ Time Frame: up to 43 months ]
    Treatment period thought end of study, up to 43 months
  • Changes in Health [ Time Frame: up to 43 months ]
    Treatment period thought end of study, up to 43 months
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: November 29, 2017)
  • Platelet Count [ Time Frame: up to 43 months ]
    Treatment period thought end of study, up to 43 months
  • Change in Clinical Outcome Assessments (COA) Score [ Time Frame: up to 17 weeks ]
    Change in Patient Global Assessment-CIT (PGA-CIT) scores from week 1 (baseline) to weeks 2 and 3.
    1. 4-item instrument designed to assess global change in quality of life and symptoms over time (since the previous clinic visit).
    2. The amount of change is rated using a 7-point Likert-style scale ranging from 1 (very much worse) to 7 (very much better). Items are scored as single items with higher scores indicating a greater degree of improvement.
  • Change in Health-Related Quality of Life (HRQoL) Score [ Time Frame: up to 17 weeks ]
    Change in Patient Global Assessment-CIT (PGA-CIT) scores from week 1 (baseline) to weeks 2 and 3.
    1. 4-item instrument designed to assess global change in quality of life and symptoms over time (since the previous clinic visit).
    2. The amount of change is rated using a 7-point Likert-style scale ranging from 1 (very much worse) to 7 (very much better). Items are scored as single items with higher scores indicating a greater degree of improvement.
  • Romiplostim Concentration [ Time Frame: up to 17 weeks ]
    Through treatment period, up to 17 weeks
  • Change in Clinical Outcome Assessments (COA) Score [ Time Frame: Up to 17 weeks ]
    European Quality of Life-5 Dimensions (EQ-5D) scores from week 1 (baseline) to weeks 2 and 3.
    1. The EQ-5D provides a simple descriptive health profile and a single index value for health status. The EQ-5D descriptive health profile comprises 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension comprises 3 levels (no problems, some/moderate problems, extreme problems). A unique EQ-5D-3L health state is defined by combining one level from each of the 5 dimensions.
    2. EQ-5D Index values range from -0.59 to 1.00. In addition, the EQ-5D includes a single item visual analogue scale item that records the subject's self-rated health status on a vertical graduated (0 to 100) line. Higher EQ-5D index and visual analogue scale scores represent better health status.
  • Change in Clinical Outcome Assessments (COA) Score [ Time Frame: Up to 17 weeks ]
    Change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores from week 1 (baseline) to weeks 2 and 3. Version 4 (for patients with thrombocytopenia) and 2) a patient global assessment - CIT (PGA-CIT) instrument
    1. The FACT-Th18 is a 45-item instrument that includes 28 FACT general items covering 4 domains (physical well-being, social/family well-being, emotional well-being, and functional well-being) with an additional 17 items covering Additional Concerns, 15 of which specific to thrombocytopenia.
    2. Scale scores range from 0 (Not at all) to 4 (Very Much) and can be derived for each of the 4 FACT--G domains, a FACT-G total score, a thrombocytopenia subscale score, and a FACT-Th total score. The FACT-Th has been evaluated as a reliable and valid measure for assessing the impact of thrombocytopenia on patients' lives that can distinguish cancer patients with and without thrombocytopenia and is responsive to increase in platelet count over time.
  • Change in Health-Related Quality of Life (HRQoL) Score [ Time Frame: up to 17 weeks ]
    European Quality of Life-5 Dimensions (EQ-5D) scores from week 1 (baseline) to weeks 2 and 3.
    1. The EQ-5D provides a simple descriptive health profile and a single index value for health status. The EQ-5D descriptive health profile comprises 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension comprises 3 levels (no problems, some/moderate problems, extreme problems). A unique EQ-5D-3L health state is defined by combining one level from each of the 5 dimensions.
    2. EQ-5D Index values range from -0.59 to 1.00. In addition, the EQ-5D includes a single item visual analogue scale item that records the subject's self-rated health status on a vertical graduated (0 to 100) line. Higher EQ-5D index and visual analogue scale scores represent better health status.
  • Change in Health-Related Quality of Life (HRQoL) Score [ Time Frame: up to 17 weeks ]
    Change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores from week 1 (baseline) to weeks 2 and 3. Version 4 (for patients with thrombocytopenia) and 2) a patient global assessment - CIT (PGA-CIT) instrument
    1. The FACT-Th18 is a 45-item instrument that includes 28 FACT general items covering 4 domains (physical well-being, social/family well-being, emotional well-being, and functional well-being) with an additional 17 items covering Additional Concerns, 15 of which specific to thrombocytopenia.
    2. Scale scores range from 0 (Not at all) to 4 (Very Much) and can be derived for each of the 4 FACT--G domains, a FACT-G total score, a thrombocytopenia subscale score, and a FACT-Th total score. The FACT-Th has been evaluated as a reliable and valid measure for assessing the impact of thrombocytopenia on patients' lives that can distinguish cancer patients with and without thrombocytopenia and is responsive to increase in platelet count over time.
 
Descriptive Information
Brief Title  ICMJE Study of Romiplostim for Chemotherapy-induced Thrombocytopenia in Adult Subjects With Gastrointestinal, Pancreatic, or Colorectal Cancer
Official Title  ICMJE 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
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chemotherapy-induced Thrombocytopenia
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Biological: Romiplostim
  • 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.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 29, 2017)
162
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 1, 2023
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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, 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. 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 platelet count < 75 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 central laboratory assessment at screening.
  • Known active chronic hepatitis B or C 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 (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 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 central laboratory during screening.
  • 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 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 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com
Listed Location Countries  ICMJE Argentina,   Austria,   Brazil,   Bulgaria,   Canada,   Colombia,   Greece,   Hungary,   Italy,   Mexico,   Peru,   Poland,   Portugal,   Romania,   Russian Federation,   Spain,   Turkey,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03362177
Other Study ID Numbers  ICMJE 20140346
2017-002992-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
URL: https://www.amgen.com/datasharing
Responsible Party Amgen
Study Sponsor  ICMJE Amgen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP