Adavosertib Before Surgery for Ovarian Cancer

Not currently recruiting at 9 trial locations

Overseen By Shannon Westin, MD

Age: 18+

Sex: Female

Trial Phase: Phase < 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Herbal supplements, Statins

Disqualifiers: Other active cancers, CNS disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 28 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how a drug called adavosertib affects the DNA of cancer cells in patients with advanced ovarian, fallopian tube, or primary peritoneal cancer. The goal is to determine if altering the cancer cell's DNA can help doctors plan better treatments. Eligible patients have advanced high-grade serous ovarian, fallopian tube, or primary peritoneal cancer and have not received prior treatment for these conditions. As an Early Phase 1 trial, this research aims to understand how adavosertib works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires stopping certain medications, especially those affecting liver enzymes like CYP3A4 and P-glycoprotein, two weeks before starting and during the study. Herbal supplements and statins like atorvastatin are also not allowed. It's best to discuss your current medications with the trial team to see if any need to be paused.

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

Research shows that adavosertib has been tested in people with various advanced cancers. Studies have found that adavosertib is generally safe when combined with chemotherapy for solid tumors. However, some patients experienced problems with a higher dose of 300 mg daily. This higher dose was not well-tolerated and raised safety concerns.

In simpler terms, adavosertib can be safe at certain doses, but higher amounts might cause issues. Prospective trial participants should know that researchers are aware of these concerns and are likely adjusting doses to balance effectiveness and safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Adavosertib is unique because it targets a protein called WEE1, which plays a key role in cell division. Unlike traditional chemotherapy for ovarian cancer, which attacks rapidly dividing cells indiscriminately, adavosertib specifically disrupts cancer cell growth by interfering with the cell cycle. Researchers are excited about this treatment because it offers a more targeted approach, potentially leading to fewer side effects and better outcomes for patients. Additionally, adavosertib is taken orally, which could offer more convenience compared to intravenous chemotherapy.

What evidence suggests that adavosertib might be an effective treatment for advanced ovarian cancer?

Research suggests that adavosertib, which participants in this trial will receive, could be a promising treatment for ovarian cancer. In earlier studies, 63.8% of patients who had already received treatment for ovarian cancer experienced stabilization or improvement in their condition with adavosertib. This means that many patients saw their disease stop progressing or get better. Another study found that 29.4% of patients had a noticeable reduction in tumor size. Adavosertib targets an enzyme that helps cancer cells grow, which might explain these encouraging results. Although more research is needed, these early findings indicate it may help manage aggressive ovarian cancers. ^{1 2 4 5 6}

Who Is on the Research Team?

Shannon Westin, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for women with advanced high-grade ovarian, fallopian tube, or primary peritoneal cancer who haven't had prior treatment for these conditions. Participants must be able to swallow pills, use effective contraception if of childbearing potential, and have no gastrointestinal issues affecting medication absorption. They should understand the study and consent to it, meet certain health criteria including an ECOG status of 0 or 1, and be scheduled for surgery within a specific timeframe.

Inclusion Criteria

Patients must be able to understand and willing to sign an informed consent

Patients must be able to swallow and tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of AZD1775

Women of childbearing potential (WoCBP) may be included only if acceptable contraception is in place

Exclusion Criteria

Unsuitability or non-compliance as judged by the investigator

Specific restrictions on drug use and co-administration

You have other cancers that are currently being treated, unless certain exceptions apply.

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, with potential additional cycles on days 8-12, 15-19, and 22-26, followed by standard of care laparoscopy

Up to 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days and then every 3 months thereafter

What Are the Treatments Tested in This Trial?

Interventions

• Adavosertib

Trial Overview The trial is testing how adavosertib affects tumor DNA in patients undergoing surgery for aggressive cancers of the ovary, fallopian tube, or peritoneum. It's an early phase I pilot study aimed at understanding DNA characteristics that influence treatment response to help plan better therapies.

How Is the Trial Designed?

Group I: Treatment (adavosertib) Experimental Treatment 2 Interventions

Patients receive adavosertib PO QD on days 1-5. Patients then undergo standard of care laparoscopy. Patients may also receive adavosertib PO QD on days 8-12, 15-19, and 22-26 for up to 28 days based on surgery schedule.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The combination of carboplatin and adavosertib was found to be safe and effective in treating patients with TP53 mutated platinum-resistant ovarian cancer, showing an objective response rate of 41% among 29 evaluable patients.

Despite its efficacy, the treatment was associated with significant bone marrow toxicity, which was the most common reason for dose reductions and delays, highlighting a safety concern that needs to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

WEE1 inhibitor adavosertib in combination with carboplatin in advanced TP53 mutated ovarian cancer: A biomarker-enriched phase II study. Embaby, A., Kutzera, J., Geenen, JJ., et al.[2023]

In a study of 28 patients with platinum-resistant recurrent epithelial ovarian cancer, apatinib treatment led to a median progression-free survival of 6.0 months when used as maintenance therapy and 3.0 months as salvage therapy, indicating moderate efficacy in extending survival.

The most common side effects of apatinib included hand-foot syndrome (53.57%) and secondary hypertension (46.43%), with some patients experiencing severe toxicities that led to treatment discontinuation or dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy And Safety Of Apatinib Treatment In Platinum-Resistant Recurrent Epithelial Ovarian Cancer: A Real World Study. Zhang, J., Li, A., Jiang, Q., et al.[2022]

Adavosertib, when combined with carboplatin, showed a high overall response rate of 66.7% in patients with platinum-resistant ovarian cancer, indicating promising efficacy for this treatment combination.

However, the combination therapy resulted in significant hematologic toxicities, such as neutropenia and anemia, suggesting that while adavosertib is effective, careful monitoring and further optimization of treatment protocols are necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adavosertib with Chemotherapy in Patients with Primary Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer: An Open-Label, Four-Arm, Phase II Study. Moore, KN., Chambers, SK., Hamilton, EP., et al.[2022]

Optimal surgical debulking to achieve no residual disease (R0) significantly improves survival rates in patients with epithelial ovarian cancer, which is crucial given its high mortality rate.

The SOLO-1 trial demonstrated that olaparib, a maintenance therapy, significantly reduces the risk of disease progression by 70% in patients with advanced ovarian cancer who have BRCA mutations, highlighting its efficacy in targeted treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodal Treatment of Primary Advanced Ovarian Cancer. Friedrich, M., Friedrich, D., Kraft, C., et al.[2021]

Citations

1. cancertreatmentreviews.com cancertreatmentreviews.com/article/S0305-7372(23)00022-1/pdf

A systematic review Six records reported efficacy results of WEE1i in gynecological malignancies (n = 6). Objective response rates of adavosertib monotherapy or in ...

2. 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 ...

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

ADAGIO: A Phase IIb, Open-Label, Single-Arm, Multicenter ... In a previous phase II study, adavosertib demonstrated preliminary activity (ORR, 29.4%) and tolerability in patients with recurrent USC at a ...

4. 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9445195/

Effects of Wee1 inhibitor adavosertib on patient-derived ... Our findings presented here indicate that adavosertib inhibits HGSOC cell growth at multiple levels. Importantly, the effect in our study material is ...

6. 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.