Avatrombopag for Thrombocytopenia in Gastrointestinal Cancer

(ACT-GI Trial)

Recruiting in Palo Alto (17 mi)

+6 other locations

Overseen by Gerald A Soff, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Hanny Al-Samkari, MD

Must not be taking: Thrombopoietin receptor agonists

Disqualifiers: Hematologic malignancy, Bone marrow invasion, others

No Placebo Group

Prior Safety Data

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}

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 am 18 years old or older.

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.

Trial 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 (Thrombopoietin Receptor Agonist)
• Matching Placebo (Other)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Cleveland Clinic Cleveland, OH

Yale New Haven Hospital New Haven, CT

University of Miami Sylvester Comprehensive Cancer Center Miami, FL

University of Miami Cancer Center Miami, FL

More Trial Locations

Who Is Running the Clinical Trial?

Hanny Al-Samkari, MD Lead Sponsor

Swedish Orphan Biovitrum Industry Sponsor

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] Objective: To review the pharmacology, pharmacokinetics, clinical efficacy, safety, dosing and administration, and place in therapy of avatrombopag for the treatment of immune thrombocytopenia and chronic liver disease-associated thrombocytopenia. Summary: Avatrombopag is an orally administered thrombopoietin receptor agonist approved for the treatment of immune thrombocytopenia and is the first oral thrombopoietin receptor agonist approved for the treatment of perioperative thrombocytopenia associated with chronic liver disease in adults. The efficacy and safety of avatrombopag has been demonstrated in a multicenter, randomized, double blind, placebo-controlled phase III study in the setting of immune thrombocytopenia and in 2 identically designed, multicenter, randomized, double blind, placebo-controlled phase III trials in the setting of thrombocytopenia associated with chronic liver disease. The most common adverse events reported in the clinical trials were headache, fatigue, and gastrointestinal toxicities. The incidence of bleeding events was comparable between the avatrombopag and placebo treatment groups in each study. Avatrombopag has not been shown to be associated with hepatoxicity and does not require food restriction like the other oral thrombopoietin receptor agonist for immune thrombocytopenia, eltrombopag. Also, unlike eltrombopag for immune thrombocytopenia, it can be dosed less frequently than once daily. Conclusion: Avatrombopag offers another safe and effective oral option for the treatment of immune thrombocytopenia without food restrictions and an alternative, transfusion-sparing option for thrombocytopenia associated with chronic liver disease patients undergoing surgery.

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] Background: Avatrombopag is a novel oral, nonpeptide thrombopoietin receptor agonist (TPO-RA). A few studies have shown that avatrombopag is effective against thrombocytopenia. However, no systematic review has been conducted on the efficacy and safety of avatrombopag. Therefore, the aim of this study was to comprehensively assess the efficacy and safety of avatrombopag patients with thrombocytopenia. Methods: Databases including Medline, PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were searched for randomized controlled trials that compared avatrombopag with placebo in patients with thrombocytopenia. The deadline was March 2019. Results: In total, 743 patients were analyzed in five clinical trials. Patients treated with avatrombopag achieved higher platelet response (OR: 17.71, 95% CI [11.01 to 28.48], p < 0.00001) than with placebo. Avatrombopag produced an absolute increment in platelet count (WMD: 31.13%, 95% CI [22.27 to 39.99], p < 0.00001) unlike the placebo. In addition, the incidence of serious adverse events (RR: 1.18, 95% CI [0.72 to 1.93], p = 0.51) and deaths (RR: 0.93, 95% CI [0.19 to 4.45], p = 0.93) in patients treated with avatrombopag was not significantly different from that in patients treated with placebo. The incidence of adverse events in patients treated with avatrombopag was slightly higher than that in patients treated with placebo (RR: 1.25, 95% CI [1.05 to 1.49], p = 0. 01) after one trial with high heterogeneity was removed. Conclusions: This meta-analysis showed that avatrombopag was an effective treatment for thrombocytopenia, but there is sufficient evidence to indicate that adverse events may occur.

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

Avatrombopag: First Global Approval. [2019] Avatrombopag (Doptelet®) is an orally bioavailable, small molecule thrombopoietin receptor agonist that has been developed by Dova Pharmaceuticals for the treatment of thrombocytopenic disorders. In May 2018 avatrombopag received its first global approval, in the USA, for use in the treatment of thrombocytopenia in adult patients with chronic liver disease (CLD) who are scheduled to undergo a procedure. A Marketing Authorization Application for use of avatrombopag in this indication was submitted to the EMA in April 2018. Clinical development of avatrombopag in the treatment of other thrombocytopenic disorders, including immune thrombocytopenic purpura and chemotherapy-induced thrombocytopenia, is ongoing. This article summarizes the milestones in the development of avatrombopag leading to this first approval for the treatment of thrombocytopenia in adult patients with CLD.

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

Avatrombopag: A Review in Thrombocytopenia. [2022] Avatrombopag (Doptelet®) is an orally administered second generation thrombopoietin receptor agonist (TPO-RA) approved for the treatment of primary chronic immune thrombocytopenia (ITP) in adult patients who are refractory or have an unsatisfactory response to other treatments, as well as for the treatment of thrombocytopenia in adult patients with chronic liver disease (CLD) scheduled to undergo an invasive procedure. In phase III studies, avatrombopag was associated with a significantly greater platelet response than placebo in patients with chronic ITP, and was superior to placebo in reducing the requirement for platelet transfusion or rescue procedures for bleeding caused by surgery in patients with CLD with a platelet count < 50 × 109/L at baseline. Longer term data indicate that avatrombopag is associated with high durable response rates in ITP and may have corticosteroid-sparing effects. The drug was generally well tolerated in both indications. Avatrombopag thus represents a convenient and effective second-line treatment for patients with chronic ITP and can prevent bleeding events in patients with CLD scheduled to undergo a procedure, offering a useful alternative to other available treatments in both indications.

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

Avatrombopag for the treatment of immune thrombocytopenia and thrombocytopenia of chronic liver disease. [2020] Avatrombopag is an orally-administered small molecule thrombopoietin receptor agonist. It was the third thrombopoietin receptor agonist approved for the treatment of immune thrombocytopenia and the first approved to treat periprocedural thrombocytopenia in patients with chronic liver disease (thereby providing an alternative to blood transfusions for these patients). Unlike eltrombopag, avatrombopag does not require a 4 hr food-restricted window around its use and it has not been associated with hepatotoxicity in ITP patients or portal vein thrombosis in patients with chronic liver disease. In ITP patients it can often be dosed less frequently than once daily. It is overall well-tolerated with a side-effect profile similar to placebo in randomized clinical trials. This article will review the clinical development, efficacy, safety, and pharmacology of avatrombopag for use in patients with ITP and thrombocytopenia of chronic liver disease.

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] Label="Background" NlmCategory="UNASSIGNED">Avatrombopag has been approved in patients who have severe thrombocytopenia (<50 × 109/L) and chronic liver disease (CLD) while receiving invasive procedures. The real-world application and effectiveness of avatrombopag in the subgroup patients with liver cancer remain unknown.