Adavosertib for Cancer

Recruiting at 28 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors/inducers, Statins

Disqualifiers: CNS disease, Cardiac diseases, 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: Unknown

Duration: 21-day cycles, up to 2 years

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies how well adavosertib works in patients with advanced or metastatic solid tumors that lack the SETD2 gene. Adavosertib may help stop tumor growth by blocking enzymes needed for cancer cells to grow. Adavosertib is a first-in-class, small-molecule reversible inhibitor of WEE1 kinase, previously shown to have clinical activity in various cancers.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, especially those that affect the CYP3A4 enzyme, at least 2 weeks before starting the study and throughout the trial. Herbal supplements like St. John's wort and certain cholesterol medications are also prohibited.

What makes the drug Adavosertib unique for cancer treatment?

Adavosertib is unique because it is the first small-molecule inhibitor of WEE1 kinase, which plays a role in controlling cell division. This drug is particularly promising for cancers with specific genetic mutations, like RAS and TP53, as it targets the DNA replication process that these mutations affect. ^{1 2 3 4 5}

Research Team

Rahul R Aggarwal

Principal Investigator

Yale University Cancer Center LAO

Eligibility Criteria

This trial is for adults with advanced solid tumors that have spread and have a SETD2 mutation. They must have tried at least one therapy, be able to swallow pills, not be pregnant or breastfeeding, use contraception if fertile, and meet certain health criteria like specific blood cell counts.

Inclusion Criteria

I am a male willing to use condoms during the study and for 3 months after it ends.

Your liver enzymes (AST and ALT) are not more than three times the normal levels, or not more than five times the normal levels if you have liver metastases.

I have advanced kidney cancer with a specific genetic change and have had previous treatment.

Exclusion Criteria

I am not on any cancer treatments except possibly LHRH analogues for over 6 months.

I haven't had major surgery in the last 28 days or minor surgery in the last 7 days.

I do not have active brain cancer or symptoms from previous brain metastases.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adavosertib orally once daily on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

21-day cycles, up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Adavosertib

Trial Overview The trial is testing Adavosertib's effectiveness on patients with SETD2-deficient advanced solid tumors. It's a phase II study where the drug aims to block enzymes needed for tumor growth.

Participant Groups

Group I: Treatment (adavosertib) Experimental Treatment 1 Intervention

Patients receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase I trial involving 37 children and adolescents with relapsed or refractory solid tumors, the maximum tolerated dose (MTD) of adavosertib combined with irinotecan was determined to be 85 mg/m2 and 90 mg/m2, respectively, with common side effects including hematologic and gastrointestinal issues.

The combination treatment showed promising results, with one patient achieving a partial response and two others maintaining stable disease for at least six cycles, indicating potential efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Clinical Trial of the Wee1 Inhibitor Adavosertib (AZD1775) with Irinotecan in Children with Relapsed Solid Tumors: A COG Phase I Consortium Report (ADVL1312). Cole, KA., Pal, S., Kudgus, RA., et al.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Effect of food on the pharmacokinetics of the WEE1 inhibitor adavosertib (AZD1775) in patients with advanced solid tumors. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Adavosertib (AZD1775) does not prolong the QTc interval in patients with advanced solid tumors: a phase I open-label study. [2023]

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

Uterine Serous Carcinoma Responds to the WEE1 Inhibitor Adavosertib. [2021]

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

Inhibition of WEE1 Is Effective in TP53- and RAS-Mutant Metastatic Colorectal Cancer: A Randomized Trial (FOCUS4-C) Comparing Adavosertib (AZD1775) With Active Monitoring. [2022]

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

Phase I Clinical Trial of the Wee1 Inhibitor Adavosertib (AZD1775) with Irinotecan in Children with Relapsed Solid Tumors: A COG Phase I Consortium Report (ADVL1312). [2021]