Adavosertib for Cancer

Not currently recruiting at 33 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called adavosertib for individuals with a specific type of advanced cancer that has a mutation in the SETD2 gene. Adavosertib aims to stop tumor growth by blocking enzymes that aid cancer cell growth. The trial seeks participants with solid tumors, including a type of kidney cancer, who have already tried other treatments. Participants must have the SETD2 mutation confirmed by genetic testing and have cancer that has spread to other parts of the body. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

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.

Is there any evidence suggesting that adavosertib is likely to be safe for humans?

Research has shown that adavosertib was safe in earlier studies. In one study, patients tolerated a daily dose of 200 mg well, with no new safety issues. However, a higher dose of 300 mg per day proved more difficult for patients to handle. This finding highlights the importance of dosage in patient tolerance. While the treatment may help slow tumor growth, participants should be aware of possible side effects, especially at higher doses. Participants should consult their healthcare provider to understand what joining the trial might involve. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Adavosertib is unique because it targets the WEE1 kinase, a protein involved in cell cycle regulation, making it different from many standard cancer treatments that often target DNA or hormone receptors. This mechanism could help prevent cancer cells from repairing themselves after damage, potentially leading to their destruction. Researchers are excited about adavosertib because it offers a new way to attack cancer cells, especially in tumors resistant to other treatments. Plus, its oral administration makes it convenient compared to some treatments that require infusion.

What evidence suggests that adavosertib might be an effective treatment for advanced/metastatic SETD2-deficient solid tumors?

Research has shown that adavosertib, the treatment under study in this trial, may help treat certain cancers. In one study, 22% of patients with a specific type of tumor (SETD2-deficient) experienced slight tumor shrinkage. Additionally, 56% of these patients maintained stable disease, meaning their cancer did not progress during treatment. Another study found that adavosertib helped control the disease in 63.8% of patients with ovarian cancer. While adavosertib has shown early signs of effectiveness against tumors, it has also caused some side effects. Overall, the evidence suggests that adavosertib might effectively slow tumor growth in certain cancers. ^{1 2 3 5 6}

Who Is on the Research Team?

Rahul R Aggarwal

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10345044/

A Phase Ib Study Assessing the Safety, Tolerability, and ...

An overall DCR of 63.8% was observed across all cohorts, which included patients who had been previously treated for ovarian cancer (including ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO-24-01606

ADAGIO: A Phase IIb, Open-Label, Single-Arm, Multicenter ...

Adavosertib showed some antitumor activity in patients with recurrent/persistent USC. However, at 300 mg once daily dosing, it was not well tolerated in this ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2352578925001213

Phase 2 study of Wee1 inhibitor adavosertib in recurrent ...

Overall, UCS carries a poor prognosis with a recurrence rate of 37 % in stage I disease and up to 80 % in stage IV disease, with dismal 5 year overall survival ...

4.

aacrjournals.org

aacrjournals.org/cancerrescommun/article/4/7/1793/746640/A-Phase-II-Trial-of-the-WEE1-Inhibitor-Adavosertib

A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2 ...

Minor tumor regressions were observed in 4/18 (22%) evaluable patients. Stable disease (SD) was the best overall response in 10/18 (56%) ...

5.

onclive.com

onclive.com/view/adavosertib-shows-early-antitumor-activity-despite-safety-concerns-in-uterine-serous-carcinoma

Adavosertib Shows Early Antitumor Activity Despite Safety ...

Adavosertib demonstrated a 26% ORR in heavily pretreated uterine serous carcinoma patients, but was poorly tolerated at 300 mg daily.

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S2468294224000212

Safety, tolerability, pharmacokinetics, and antitumor activity ...

Adavosertib 200 mg once daily was well tolerated, with no new safety concerns. •. Adavosertib monotherapy had limited antitumor activity in this patient ...