Avatrombopag for Thrombocytopenia in Gastrointestinal Cancer

(ACT-GI Trial)

Not currently recruiting at 6 trial locations

Overseen By Gerald Soff, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hanny Al-Samkari, MD

Must not be taking: Thrombopoietin receptor agonists

Disqualifiers: Hematologic malignancy, Bone marrow invasion, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of Avatrombopag compared to a placebo for treating chemotherapy-induced thrombocytopenia (low platelet count) in individuals with gastrointestinal cancer undergoing chemotherapy. The goal is to determine if Avatrombopag can increase platelet counts to safe levels, enabling patients to continue their chemotherapy treatments. Individuals with ongoing low platelet counts due to chemotherapy for specific types of gastrointestinal cancer might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, you must not have taken any thrombopoietin receptor agonists within 14 days of starting the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Avatrombopag is generally safe for individuals with gastrointestinal cancer. In earlier studies, patients taking Avatrombopag required fewer platelet transfusions than those on a placebo. This indicates that Avatrombopag can increase platelet levels without causing serious side effects. Additionally, the FDA has approved Avatrombopag for other uses, such as treating chronic immune thrombocytopenia, a condition characterized by low platelet counts. This approval suggests its safety for patients. Always consult a doctor to determine if joining a trial is appropriate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for thrombocytopenia?

Unlike the standard treatments for thrombocytopenia in gastrointestinal cancer, which often rely on transfusions or steroids, Avatrombopag offers a unique approach. It works by stimulating the body’s own production of platelets through the thrombopoietin receptor pathway, potentially reducing the need for external platelet sources. This mechanism not only aims to increase platelet counts more naturally but also promises to do so with fewer side effects. Researchers are excited because Avatrombopag could provide a more sustainable and less invasive option for managing thrombocytopenia in these patients.

What evidence suggests that this trial's treatments could be effective for Chemotherapy-Induced Thrombocytopenia in gastrointestinal cancer?

Research shows that avatrombopag, which participants in this trial may receive, effectively treats low platelet counts caused by chemotherapy, known as chemotherapy-induced thrombocytopenia (CIT). Studies have found that avatrombopag significantly boosts platelet counts in patients with gastrointestinal cancer compared to those who do not take it. One study showed that avatrombopag improved platelet levels more than a placebo did. It is also considered safe and well-tolerated by patients. These findings suggest that avatrombopag can help manage low platelet counts due to chemotherapy. ^{4 6 7 8 9}

Who Is on the Research Team?

Hanny Al-Samkari, MD

Principal Investigator

Massachusetts General Hospital

Gerald A Soff, MD

Principal Investigator

University of Miami Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with gastrointestinal cancers who are undergoing chemotherapy and have a low platelet count, known as Chemotherapy-Induced Thrombocytopenia (CIT). They must not have certain blood disorders or be planning to receive other investigational drugs. Participants should not be pregnant, breastfeeding, or have had recent bleeding events.

Inclusion Criteria

I can care for myself and doctors expect me to live more than 12 weeks.

I have low platelet counts due to chemotherapy for over a month.

I haven't had chemotherapy in the last 14 days, with certain exceptions.

Exclusion Criteria

Pregnancy or breastfeeding

I have had blood cancer in the past.

I received a platelet transfusion within the last 3 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Lead-In Period

Participants receive a pre-determined dose of Avatrombopag or matching placebo daily to assess initial platelet count recovery

2 weeks

2 visits (in-person)

On-Cycle Period

Participants continue receiving Avatrombopag or placebo daily to maintain platelet count during chemotherapy cycles

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 weeks

2 visits (in-person)

Open-label extension (optional)

Participants may opt into receiving Avatrombopag through a special free drug program

What Are the Treatments Tested in This Trial?

Interventions

• Avatrombopag
• Matching Placebo

Trial Overview

The study compares Avatrombopag, a drug that stimulates platelet production, against a placebo in patients with CIT from GI cancer treatments. The goal is to see if Avatrombopag can better manage low platelet counts during chemotherapy cycles.

How Is the Trial Designed?

Group I: Group A - Avatromopag Experimental Treatment 1 Intervention

30 participants will be randomized into a 1:1 fashion and will be stratified based on the number of cytotoxic agents in the patient's chemotherapy regimen. Participants will complete study procedures as outlined: Lead-In Period (Day 1 - 15) * Pre-determined dose of Avatrombopag 1x daily. * Participants failing to achieve a platelet count ≥100,000/µL within 2 weeks will be considered a treatment failure (and will proceed to the end-of-study visit). On-Cycle Period (Day 15 - up to Week 6) • Pre-determined dose of Avatrombopag 1x daily. Follow-up Period * End of Treatment on-site visit. * Follow-up visit 30-42 days after End of Treatment visit.

Group II: Group B - Matching Placebo Active Control 1 Intervention

30 participants will be randomized into a 1:1 fashion and will be stratified based on the number of cytotoxic agents in the patient's chemotherapy regimen. Participants will complete study procedures as outlined: Lead-In Period (Day 1 - 15) * Pre-determined dose of matching placebo 1x daily. * Participants failing to achieve a platelet count ≥100,000/µL within 2 weeks will be considered a treatment failure (and will proceed to the end-of-study visit). On-Cycle Period (Day 15 - up to Week 6) • Pre-determined dose of matching placebo 1x daily. Follow-up Period * End of Treatment on-site visit. * Follow-up visit 30-42 days after End of Treatment visit.

Avatrombopag is already approved in United States, European Union for the following indications:

Approved in United States as Doptelet for:

• Thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a procedure
• Chronic immune thrombocytopenia

Approved in European Union as Doptelet for:

• Thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a procedure
• Chronic immune thrombocytopenia

Who Is Running the Clinical Trial?

Hanny Al-Samkari, MD

Lead Sponsor

Trials

2

Recruited

90+

Swedish Orphan Biovitrum

Industry Sponsor

Trials

103

Recruited

13,300+

Dr. Guido Oelkers

Swedish Orphan Biovitrum

Chief Executive Officer since 2017

PhD in Economics

Dr. Lydia Abad-Franch

Swedish Orphan Biovitrum

Chief Medical Officer since 2023

MD, MBA

Published Research Related to This Trial

Avatrombopag is an effective oral treatment for adults with chronic immune thrombocytopenia (ITP), showing significantly greater platelet responses compared to placebo in phase III studies.

The drug also reduces the need for platelet transfusions in patients with chronic liver disease undergoing invasive procedures, and it is generally well tolerated, making it a valuable second-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avatrombopag: A Review in Thrombocytopenia. Markham, A.[2022]

Avatrombopag is an effective oral treatment for immune thrombocytopenia (ITP) and periprocedural thrombocytopenia in chronic liver disease, providing a safer alternative to blood transfusions without the need for food restrictions.

It has a favorable safety profile, showing no significant hepatotoxicity or portal vein thrombosis, and is generally well-tolerated, with side effects similar to those of a placebo in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avatrombopag for the treatment of immune thrombocytopenia and thrombocytopenia of chronic liver disease. Cheloff, AZ., Al-Samkari, H.[2020]

Avatrombopag is an effective oral treatment for immune thrombocytopenia and chronic liver disease-associated thrombocytopenia, demonstrated in phase III clinical trials with no significant increase in bleeding events compared to placebo.

It is safer than other similar medications, as it does not require food restrictions and has not been linked to hepatotoxicity, making it a convenient option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avatrombopag for the Treatment of Immune Thrombocytopenia and Periprocedural Thrombocytopenia Associated With Chronic Liver Disease. Tran, TB., Downing, L., Elmes, JB., et al.[2022]

Avatrombopag significantly increased platelet response in patients with thrombocytopenia compared to placebo, with a notable absolute increment in platelet count of 31.13%.

While avatrombopag was effective, it was associated with a slightly higher incidence of adverse events compared to placebo, although serious adverse events and mortality rates were not significantly different.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Avatrombopag in Patients With Thrombocytopenia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Li, C., Li, X., Huang, F., et al.[2020]

Avatrombopag is effective in increasing platelet counts in liver cancer patients with severe thrombocytopenia, showing a higher responder rate in patients without chronic liver disease (100% vs. 76.4%).

The treatment was found to be safe, with no reported thrombosis or bleeding events, even in patients with portal vein tumor thrombosis, allowing for successful anticancer treatment implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Avatrombopag in Liver Cancer Patients with Severe Thrombocytopenia: Real-World Data and Challenges. Huang, A., Chen, JF., Wu, JZ., et al.[2022]

Avatrombopag (Doptelet®) is an oral medication that acts as a thrombopoietin receptor agonist, specifically designed to treat low platelet counts (thrombocytopenia) in adults with chronic liver disease who are about to undergo a medical procedure.

It received its first global approval in May 2018 in the USA, and further clinical studies are being conducted to explore its effectiveness in treating other conditions related to low platelet counts, such as immune thrombocytopenic purpura and chemotherapy-induced thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avatrombopag: First Global Approval. Shirley, M.[2019]

Citations

1.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e16334

A retrospective study on the efficacy and safety of ...

Conclusions: Avatrombopag has high efficacy and safety in the treatment of CIT in gastrointestinal cancer. rhTPO rather than rhIL-11 combined ...

2.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK608453/

Clinical Review - Avatrombopag (Doptelet) - NCBI - NIH

In 1 double-blind RCT (Study 302), treatment with avatrombopag, another TPO-RA, led to an improvement in platelet count response compared to placebo ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04896528?term=AVATROMBOPAG&rank=1

Efficacy and Safety of Avatrombopag in Cancer Patients ...

Primary outcome measure is percentage of participants whose PLT reaches ≥75×109/L, or increases by ≥50×109/L or ≥100% from baseline at least once within 20 days ...

4.

asco.org

asco.org/abstracts-presentations/ABSTRACT419884

A retrospective study on the efficacy and safety ...

Conclusions: Avatrombopag has high efficacy and safety in the treatment of CIT in gastrointestinal cancer. rhTPO rather than rhIL-11 combined with avatrombopag ...

5.

frontiersin.org

frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.970978/full

Avatrombopag for the treatment of thrombocytopenia ...

The application of avatrombopag in patients with CIT can increase the platelet count of the patients compared with baseline. Avatrombopag is safe and tolerable.

6.

doptelet.com

doptelet.com/themes/pdf/prescribing-information.pdf

Prescribing Information

In the Low Baseline Platelet Count Cohort, the mean baseline platelet count for the DOPTELET-treated group was 31.1×109/L and for the placebo-treated ...

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2024/210238s009lbl.pdf

DOPTELET® (avatrombopag) tablets, for oral use

DOPTELET is not used to make platelet counts normal in adults with chronic liver disease or chronic immune thrombocytopenia. It is not known if DOPTELET is safe ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7003278/

Avatrombopag, an Alternate Treatment Option to Reduce ...

Avatrombopag was superior to placebo in increasing patients not requiring a platelet transfusion or rescue procedure, those achieving a platelet count ≥50 × 10 ...

9.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2025/219696s000lbl.pdf

Reference ID: 5631118 - accessdata.fda.gov

Monitoring: Obtain a platelet count prior to administration of DOPTELET therapy and on the day of a procedure to ensure an adequate increase in platelet count.