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

RECITE: A Phase 3 Randomized Placebocontrolled 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

Sponsors

Lead Sponsor: Amgen

Source Amgen
Brief Summary

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

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

Overall Status Recruiting
Start Date September 30, 2019
Completion Date December 18, 2022
Primary Completion Date January 17, 2022
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Incidence of a Thrombocytopenia-induced chemotherapy dose modification during the second or third on study chemotherapy cycles. 48 days
Secondary Outcome
Measure Time Frame
Depth of Platelet Count 48 days
First platelet response 7 Days
Bleeding Events 48 days
Overall Survival 1-year
Subject incidence of Platelet Transfusion 48 days
Platelet Count 7 days
AEs/SAEs overall safety of romiplostim 36 months
Enrollment 162
Condition
Intervention

Intervention Type: Biological

Intervention Name: Romiplostim

Description: 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.

Intervention Type: Other

Intervention Name: Placebo

Description: Placebo Comparator

Arm Group Label: Placebo

Eligibility

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.

- Subjects must have a platelet count <75 x 10(9)/L on study day 1.

- 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.

- 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:

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.

- 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 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 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. 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 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.

Gender: All

Minimum Age: 18 Years

Maximum Age: 100 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
MD Study Director Amgen
Overall Contact

Last Name: Amgen Call Center

Phone: 866-572-6436

Email: [email protected]

Location
Facility: Status:
Research Site | Jonesboro, Arkansas, 72401, United States Recruiting
Research Site | Anaheim, California, 92801, United States Recruiting
Research Site | Orange City, Florida, 32763, United States Recruiting
Research Site | Alexandria, Louisiana, 71301, United States Recruiting
Research Site | New Orleans, Louisiana, 70112, United States Recruiting
Research Site | Shreveport, Louisiana, 71105, United States Recruiting
Research Site | Baltimore, Maryland, 21202, United States Recruiting
Research Site | Bethesda, Maryland, 20817, United States Recruiting
Research Site | Hattiesburg, Mississippi, 39401, United States Recruiting
Research Site | Springfield, Missouri, 65807, United States Recruiting
Research Site | Sparta, New Jersey, 07871, United States Recruiting
Research Site | Fort Worth, Texas, 76104, United States Recruiting
Research Site | Cordoba, Córdoba, 5000, Argentina Recruiting
Research Site | Viedma, Río Negro, 8500, Argentina Recruiting
Research Site | Steyr, 4400, Austria Recruiting
Research Site | Wien, 1090, Austria Recruiting
Research Site | Curitiba, Paraná, 80530-010, Brazil Recruiting
Research Site | Teresina, Piauí, 64049-200, Brazil Recruiting
Research Site | Caxias do Sul, Rio Grande Do Sul, 95020-450, Brazil Recruiting
Research Site | Campinas, São Paulo, 13010-001, Brazil Recruiting
Research Site | Sao Paulo, São Paulo, 08270-120, Brazil Recruiting
Research Site | Ruse, 7002, Bulgaria Recruiting
Research Site | Sofia, 1330, Bulgaria Recruiting
Research Site | Kitchener, Ontario, N2G 1G3, Canada Recruiting
Research Site | Medellin, Antioquia, 050030, Colombia Recruiting
Research Site | Cali, Valle Del Cauca, 760042, Colombia Recruiting
Research Site | Athens, 11526, Greece Recruiting
Research Site | Athens, 11528, Greece Recruiting
Research Site | Athens, 12462, Greece Recruiting
Research Site | Athens, 14564, Greece Recruiting
Research Site | Budapest, 1097, Hungary Recruiting
Research Site | Debrecen, 4032, Hungary Recruiting
Research Site | Szeged, 6720, Hungary Recruiting
Research Site | Milano, 20162, Italy Recruiting
Research Site | La Paz, Baja California Sur, 23040, Mexico Recruiting
Research Site | San Luis Potosi, San Luis Potosí, 78200, Mexico Recruiting
Research Site | Oaxaca, 68000, Mexico Recruiting
Research Site | Arequipa, 04001, Peru Recruiting
Research Site | Lima, 15036, Peru Recruiting
Research Site | Biala Podlaska, 21-500, Poland Recruiting
Research Site | Brzeziny, 95-060, Poland Recruiting
Research Site | Poznan, 60-569, Poland Recruiting
Research Site | Poznan, 60-780, Poland Recruiting
Research Site | Matosinhos, 4464-513, Portugal Recruiting
Research Site | Bucharest, 022328, Romania Recruiting
Research Site | Cluj-Napoca, 400015, Romania Recruiting
Research Site | Cluj-Napoca, 400124, Romania Recruiting
Research Site | Craiova, 200347, Romania Recruiting
Research Site | Iasi, 700483, Romania Recruiting
Research Site | Timisoara, 300239, Romania Recruiting
Research Site | Arkhangelsk, 163045, Russian Federation Recruiting
Research Site | Moscow Region, 143442, Russian Federation Recruiting
Research Site | Moscow, 125284, Russian Federation Recruiting
Research Site | Nizhniy Novgorod, 603089, Russian Federation Recruiting
Research Site | Pyatigorsk, 357502, Russian Federation Recruiting
Research Site | Ryazan, 390011, Russian Federation Recruiting
Research Site | Saint-Petersburg, 197758, Russian Federation Recruiting
Research Site | Sochi, 354057, Russian Federation Recruiting
Research Site | Tambov, 390013, Russian Federation Recruiting
Research Site | Granada, Andalucía, 18016, Spain Recruiting
Research Site | Salamanca, Castilla León, 37007, Spain Recruiting
Research Site | Ourense, Galicia, 32005, Spain Recruiting
Research Site | Madrid, 28050, Spain Recruiting
Research Site | Adana, 01250, Turkey Recruiting
Research Site | Ankara, 06200, Turkey Recruiting
Research Site | Ankara, 06230, Turkey Recruiting
Research Site | Ankara, 06560, Turkey Recruiting
Research Site | Ankara, 06800, Turkey Recruiting
Research Site | Edirne, 22030, Turkey Recruiting
Research Site | Istanbul, 34093, Turkey Recruiting
Research Site | Istanbul, 34732, Turkey Recruiting
Research Site | Izmir, 35100, Turkey Recruiting
Research Site | Izmir, 35575, Turkey Recruiting
Research Site | Kocaeli, 41380, Turkey Recruiting
Research Site | Samsun, 55200, Turkey Recruiting
Research Site | Chernivtsi, 58013, Ukraine Recruiting
Research Site | Ivano-Frankivsk, 76018, Ukraine Recruiting
Research Site | Uzhgorod, 88000, Ukraine Recruiting
Location Countries

Argentina

Austria

Brazil

Bulgaria

Canada

Colombia

Greece

Hungary

Italy

Mexico

Peru

Poland

Portugal

Romania

Russian Federation

Spain

Turkey

Ukraine

United States

Verification Date

September 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Romiplostim

Type: Experimental

Description: 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.

Label: Placebo

Type: Placebo Comparator

Description: 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.

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov