Avatrombopag for Thrombocytopenia in Gastrointestinal Cancer

(ACT-GI Trial)

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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

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

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 Avatrombopag safe for humans?

Avatrombopag has been shown to be generally safe in humans, with common side effects including headache, fatigue, and stomach issues. Serious side effects were not significantly different from those seen with a placebo, and it does not cause liver damage or require food restrictions. ^{1 2 3 4 5}

What makes the drug Avatrombopag unique for treating thrombocytopenia in gastrointestinal cancer?

Avatrombopag is unique because it is an oral thrombopoietin receptor agonist that does not require food restrictions and is not associated with liver toxicity, unlike some other treatments. It offers a convenient alternative to blood transfusions for patients with thrombocytopenia, especially those undergoing procedures. ^{1 3 4 5 6}

Research Team

Hanny Al-Samkari, MD

Principal Investigator

Massachusetts General Hospital

Gerald A Soff, MD

Principal Investigator

University of Miami Cancer Center

Eligibility Criteria

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

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

Exclusion Criteria

Pregnancy or breastfeeding

I have had blood cancer in the past.

I received a platelet transfusion within the last 3 days.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 (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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Avatrombopag for the Treatment of Immune Thrombocytopenia and Periprocedural Thrombocytopenia Associated With Chronic Liver Disease. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Avatrombopag in Patients With Thrombocytopenia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2020]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Avatrombopag: First Global Approval. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Avatrombopag: A Review in Thrombocytopenia. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Avatrombopag for the treatment of immune thrombocytopenia and thrombocytopenia of chronic liver disease. [2020]

6. Egypt pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Avatrombopag in Liver Cancer Patients with Severe Thrombocytopenia: Real-World Data and Challenges. [2022]