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Study of Romiplostim for Chemo-induced Thrombocytopenia in Adults Subjects With Gastrointestinal or Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT03362177
Recruitment Status : Not yet recruiting
First Posted : December 5, 2017
Last Update Posted : December 14, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
Study of Romiplostim for Chemotherapy-induced Thrombocytopenia in Adult Subjects with Gastrointestinal or Colorectal Cancer

Condition or disease Intervention/treatment Phase
Chemotherapy-induced Thrombocytopenia Biological: Romiplostim Other: Placebo Phase 3

Detailed Description:
A Phase 3 Randomized Placebo-controlled Double-blind Study of Romiplostim for the Treatment of Chemotherapy-induced Thrombocytopenia in Patients Receiving FOLFOX-based Chemotherapy for Treatment of Gastrointestinal or Colorectal Cancer

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 162 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized Placebo-controlled Double-blind Study of Romiplostim for the Treatment of Chemotherapy-induced Thrombocytopenia in Patients Receiving FOLFOX-based Chemotherapy for Treatment of Gastrointestinal or Colorectal Cancer
Estimated Study Start Date : June 21, 2019
Estimated Primary Completion Date : June 22, 2021
Estimated Study Completion Date : May 23, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Romiplostim

Arm Intervention/treatment
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.
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 cancer.

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.
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 cancer.

Other: Placebo
Placebo Comparator




Primary Outcome Measures :
  1. Incidence of either a chemotherapy dose delay or reduction [ 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.


Secondary Outcome Measures :
  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. 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. Platelet Count [ Time Frame: 7 days ]
    7 days after 3rd dose of IP with no transfusions in preceding 7 days

  4. 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 4.0 grading scale


  5. Overall Survival [ Time Frame: 1-year ]
    1-year overall survival

  6. Subject incidence of Platelet Transfusion [ Time Frame: 48 days ]
    platelet transfusion(s) during the treatment period

  7. AEs/SAEs [ Time Frame: 36 months ]
    Through end of study, up to 36 months


Other Outcome Measures:
  1. Change in Patient Global Assessment -CIT (PGA-CIT) [ Time Frame: 28 days ]

    Change in Patient Global Assessment-CIT (PGA-CIT) scores on Day 1 and 8.

    A 4-item instrument designed to assess global change in quality of life and symptoms over time (since the previous clinic visit).

    b. 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.


  2. Change in Functional Assessment of Cancer Therapy for Patients with Thrombocytopenia (FACT-Th18) [ Time Frame: 28 days ]

    Change in FACT-TH18 scores on Day 1, and 8.

    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. b. 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.


  3. Change in European Quality of Life 5 Dimension (EQ-5D) [ Time Frame: 28 days ]

    Change in European Quality of Life-5 Dimensions (EQ-5D) scores on Day 1 and 8.

    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.

    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.




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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion:

  • 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 or colorectal adenocarcinoma, defined as cancers of the esophagus, stomach, colon, or rectum. Tumor stage will not affect eligibility.
  • Subjects must be receiving a FOLFOX-based chemotherapy regimen, containing 5-FU and oxaliplatin, on a 14-day schedule. Note: Use of a FOLFOX-based combination regimen is permitted with (1) anti-angiogenic agents (such as bevacizumab) or (2) targeted therapy (such as anti-epidermal growth factor receptor agents). FOLFOXIRI-based regimens will not be allowed.
  • Subjects must have a platelet count < 75 x 109/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.
  • 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:

  • 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.
  • 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 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 chemotherapy induced thrombocytopenia (eg, chronic liver disease, prior history of immune thrombocytopenia purpura)
  • 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.
  • 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.
  • 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 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.
  • Females who are pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 30 days after treatment discontinuation or longer if required by prescribing information for chemotherapy received during the study. (Females of childbearing potential should only be included after a confirmed menstrual period and a negative highly sensitive urine pregnancy test.)
  • Females of childbearing potential unwilling to use an acceptable method of effective contraception (this will also be dependent on contraceptive requirements for chemotherapy received during the study) during treatment and for an additional 30 days after treatment discontinuation or longer if required by prescribing information for chemotherapy received during the study. Refer to Appendix 5 for additional contraceptive information.
  • Males with female partners of childbearing potential unwilling to use an acceptable method of effective contraception (this will also be dependent on contraceptive requirements for chemotherapy received during the study) during treatment and for an additional 30 days after treatment discontinuation or longer if required by prescribing information for chemotherapy received 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03362177


Contacts
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03362177     History of Changes
Other Study ID Numbers: 20140346
2017-002992-25 ( EudraCT Number )
First Posted: December 5, 2017    Key Record Dates
Last Update Posted: December 14, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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 link below.
URL: https://www.amgen.com/datasharing

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Amgen:
Chemotherapy Induced Thrombocytopenia
Gastrointestinal Cancer
Colorectal Cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Thrombocytopenia
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Blood Platelet Disorders
Hematologic Diseases