Adavosertib Before Surgery for Ovarian Cancer

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

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This pilot early phase I trial studies how adavosertib affects the tumor deoxyribonucleic acid (DNA) of patients undergoing surgery for high grade (fast growing or aggressive) ovarian, fallopian tube, or primary peritoneal cancer that has spread to other places in the body (advanced). Certain characteristics in the DNA of these patients may affect how well they respond to treatment. Learning how adavosertib affects DNA in tumor cells may help doctors plan effective 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 Adavosertib safe for humans?

Adavosertib has been studied in combination with other treatments for various cancers, including ovarian cancer, and has generally been found to be safe. Some studies reported that patients experienced side effects, but these were typically manageable. ^{1 2 3 4 5}

What makes the drug Adavosertib unique for ovarian cancer treatment?

Adavosertib is unique because it is a Wee1 kinase inhibitor that targets the G2/M checkpoint in cancer cells, making them more sensitive to chemotherapy. This mechanism is different from standard treatments like carboplatin and paclitaxel, which do not specifically target this checkpoint. ^{2 3 4 6 7}

What data supports the effectiveness of the drug Adavosertib before surgery for ovarian cancer?

Research shows that Adavosertib, when combined with chemotherapy, can enhance the effectiveness of treatment in ovarian cancer, especially in cases where the cancer is resistant to platinum-based drugs. It has been found to work well with other chemotherapy drugs, making cancer cells more sensitive to treatment. ^{1 2 3 7 8}

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

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]

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]

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. United States 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. [2022]

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

A Biomarker-enriched, Randomized Phase II Trial of Adavosertib (AZD1775) Plus Paclitaxel and Carboplatin for Women with Platinum-sensitive TP53-mutant Ovarian Cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial. [2023]

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

WEE1 inhibitor adavosertib in combination with carboplatin in advanced TP53 mutated ovarian cancer: A biomarker-enriched phase II study. [2023]

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

Efficacy And Safety Of Apatinib Treatment In Platinum-Resistant Recurrent Epithelial Ovarian Cancer: A Real World Study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

A phase I study of the Wee1 kinase inhibitor adavosertib (AZD1775) in combination with chemoradiation in cervical, upper vaginal, and uterine cancers. [2023]

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

Patient self-reporting of tolerability using PRO-CTCAE in a randomized double-blind, placebo-controlled phase II trial comparing gemcitabine in combination with adavosertib or placebo in patients with platinum resistant or refractory epithelial ovarian carcinoma. [2023]

8. Greece pubmed.ncbi.nlm.nih.gov

Multimodal Treatment of Primary Advanced Ovarian Cancer. [2021]