Trial Title:
Avatrombopag Vs. Placebo for CIT in GI Malignancies
NCT ID:
NCT05772546
Condition:
Gastrointestinal Cancer
Gastrointestinal Neoplasms
Chemotherapy-Induced Thrombocytopenia
Conditions: Official terms:
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Thrombocytopenia
Maleic acid
Conditions: Keywords:
Chemotherapy-Induced Thrombocytopenia
CIT
Gastrointestinal Malignancies
Gastrointestinal Cancer
Gastrointestinal Neoplasms
Avatrombopag
Thrombopoietin
Thrombopoietin receptor agonist
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Single (Participant)
Intervention:
Intervention type:
Drug
Intervention name:
Avatrombopag
Description:
Thrombopoietin receptor agonist, tablet taken orally.
Arm group label:
Group A - Avatromopag
Other name:
Doptelet, avatrombopag maleate
Intervention type:
Drug
Intervention name:
Matching Placebo
Description:
Lactose monohydrate, tablet taken orally.
Arm group label:
Group B - Matching Placebo
Summary:
The purpose of this study is to compare the efficacy of two study drugs, Avatrobopag
versus placebo, to treat persistent Chemotherapy-Induced Thrombocytopenia (CIT) in
patients with gastrointestinal (GI) malignancies receiving cytotoxic chemotherapy.
The names of the study drugs involved in this study are:
- Avatrombopag (a thrombopoietin receptor agonist)
- Matching placebo
Detailed description:
This is a randomized, double-blinded, placebo-controlled, multicenter phase 2 clinical
trial evaluating Avatrombopag versus placebo for Chemotherapy-Induced Thrombocytopenia
(CIT) in patients with gastrointestinal (GI) malignancies. Avatrombopag may increase or
stimulate megakaryocytes, which aid in producing blood platelets, resulting in an
increased production of platelets.
- Participants will be "randomized" into one of the study groups: Group A:
Avatrombopag or Group B: Matching placebo. Randomization means that a participant is
put into a group by chance.
- All patients who complete the study (whether they received avatrombopag or placebo)
have the opportunity to receive avatrombopag to treat CIT through a special free
drug program available only to the participants of this study.
The U.S. Food and Drug Administration (FDA) has not approved avatrombopag for CIT, but it
has been approved for other uses.
Study procedures include screening for eligibility, treatment visits, and blood tests.
Participants will receive the study treatment or placebo for up to seven weeks and will
be followed for up to 42 days after the last dose.
It is expected that about 60 people will take part in this research study.
Swedish Orphan Biovitrum (Sobi), biopharmaceutical company, is supporting this research
study by providing the study drugs and funding.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- A diagnosis of persistent chemotherapy-induced thrombocytopenia, as defined by a
platelet count of <85,000/µL on Day 1 of a chemotherapy cycle.
- Age ≥18 years at the time of informed consent. Because no dosing or adverse event
data are currently available on the use of avatrombopag for CIT in participants <18
years of age, children are excluded from this study, but may be eligible for future
pediatric trials.
- Receiving cytotoxic chemotherapy for a gastrointestinal malignancy, including
esophageal, gastric, small bowel, hepatobiliary (cholangiocarcinoma, gallbladder
carcinoma, hepatocellular carcinoma), pancreatic, or colorectal cancer. Lymphomas
are not eligible. Patients of any stage are eligible.
- The chemotherapy regimen being used to treat the patient's gastrointestinal
malignancy must be administered in 14, 21, or 28-day cycles and include at least one
of the following agents: fluorouracil, capecitabine, floxuridine,
trifluridine/tipiracil, gemcitabine, cisplatin, carboplatin, oxaliplatin,
irinotecan, liposomal irinotecan, paclitaxel, nanoalbumin-bound paclitaxel,
docetaxel, epirubicin, or doxorubicin.
- A plan to continue the current chemotherapy regimen (the regimen that resulted in
CIT) at the same dose and schedule for at least 1 more cycle if the platelet count
is adequate (>100,000/µL).
- Participant has not received cytotoxic chemotherapy in the 13 days before study Day
1, except for infusional fluorouracil in regimens with a 14-day cycle length or oral
cytotoxic chemotherapy agents. .
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (see Appendix B) and
a life expectancy of >12 weeks at screening.
- Participants must have adequate organ and marrow function as defined below. Use of
standard-of-care G-CSF and/or red cell transfusions to achieve adequate ANC and
hemoglobin levels is allowed.
- Absolute neutrophil count (ANC) ≥500/µL
- Hemoglobin ≥8 g/dL
- AST (SGOT) and ALT (SGPT) ≤5 × institutional ULN
- Total bilirubin ≤3 × institutional ULN
- The effects of avatrombopag on the developing human fetus are unknown. For this
reason, women of child-bearing potential and men (except for a vasectomized man with
confirmed azoospermia) must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) prior to study entry, for the duration of study
participation, and for the 30 days after discontinuation of study drug. Should a
woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician immediately.
- Participant is willing and able to comply with the study protocol.
- Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
- Participant has a history of hematologic malignancy, including leukemia, lymphoma,
myeloma, myelodysplastic syndrome, or a myeloproliferative neoplasm, with the
exception of a non-clinically significant neoplasm in the judgement of the
investigator (e.g., indolent B-cell neoplasm not requiring treatment, monoclonal
gammopathy of undetermined significance, etc.).
- Participant has known bone marrow invasion by tumor or multiple (greater than 1)
bony metastatic lesions. Participants do not need to undergo screening with bone
marrow biopsy or imaging to satisfy this criterion.
- Participant has received prior irradiation directly to the pelvic bones of a dose of
>20 Gy.
- Participants with a history of a prior major venous thromboembolic event, such as a
deep vein thrombosis or pulmonary embolism, or symptomatic arterial thrombotic
events such as a myocardial infarction, ischemic cerebral vascular accident or
transient ischemic attack will be ineligible if they have not tolerated
anticoagulation therapy. If patients remain on anticoagulation or have completed the
prescribed course of anticoagulation, they will be eligible for enrollment. A venous
thrombotic event associated with a central venous catheter or a superficial venous
thrombosis will not make the patient ineligible.
- Participant has spontaneous recovery of the platelet count to >100,000/µL prior to
randomization.
- Participant has any known clinically significant acute or active bleeding (e.g.
gastrointestinal or central nervous system) within 7 days prior to consent.
- Participants who are receiving any other investigational agents or have received any
other investigational agent within 30 days of study Day 1.
- History of hypersensitivity reactions to avatrombopag or any of its excipients.
- Participants with uncontrolled intercurrent illness, in the opinion of the
investigator.
- Participants with psychiatric illness/social situations that would limit compliance
with study requirements, in the opinion of the investigator.
- Pregnant women are excluded from this study because the effect of avatrombopag on
the developing fetus are unknown. Because there is an unknown but potential risk for
adverse events in nursing infants secondary to treatment of the mother with
avatrombopag, breastfeeding should be discontinued if the mother is treated with
avatrombopag. Pregnancy status will be assessed with a serum B-HCG pregnancy test in
women of child-bearing potential (see Section 10 for timing). Women who are
menopausal or perimenopausal will have follicle-stimulating hormone levels drawn to
confirm menopausal status.
- Participant has received a platelet transfusion within 3 days of study Day 1.
- Participant is unable to take oral medication.
- Participant has received a thrombopoietin receptor agonist (romiplostim,
eltrombopag, avatrombopag, or lusutrombopag) for any reason within 14 days of study
Day 1.
- Participant has a history of active chronic platelet disorders or thrombocytopenia
due to an etiology other than CIT, in the opinion of the investigator.
- Any other medical condition or factor that, in the opinion of the investigator, is
likely to interfere with completion of the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Yale New Haven Hospital
Address:
City:
New Haven
Zip:
06510
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Stephen Lattanzi, M.D.
Facility:
Name:
University of Miami Sylvester Comprehensive Cancer Center
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gerald A Soff, MD
Phone:
305-243-1038
Email:
gas199@med.miami.edu
Contact backup:
Last name:
Gerald A Soff, MD
Facility:
Name:
Massachusetts General Hospital Cancer Center
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hanny Al-Samkari, MD
Phone:
857-242-0719
Email:
hal-samkari@mgh.harvard.edu
Contact backup:
Last name:
Hanny Al-Samkari, MD
Facility:
Name:
Oregon Health and Science University Hospital
Address:
City:
Portland
Zip:
97239
Country:
United States
Status:
Recruiting
Contact:
Last name:
Joseph Shatzel, M.D.
Email:
shatzel@ohsu.edu
Contact backup:
Last name:
Joseph Shatzel, M.D.
Facility:
Name:
University of Washington Fred Hutchinson Cancer Center
Address:
City:
Seattle
Zip:
98195
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Sandhya Panch, M.D.
Start date:
November 1, 2023
Completion date:
July 31, 2025
Lead sponsor:
Agency:
Hanny Al-Samkari, MD
Agency class:
Other
Collaborator:
Agency:
Swedish Orphan Biovitrum
Agency class:
Industry
Source:
Massachusetts General Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05772546
