AZD1775 for Uterine Cancer

Overseen By DFCI Clinical Trials Hotline

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A4 drugs, Herbal supplements

Disqualifiers: Brain metastases, Cardiac diseases, HIV, 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: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the potential of AZD1775, an investigational drug, as a treatment for uterine cancer. It focuses on different types of uterine cancer, including uterine serous carcinoma and carcinosarcoma, which have returned or persisted after treatment. Participants will take AZD1775 orally in a specific cycle to determine its effectiveness in managing their condition. Those with uterine serous carcinoma or carcinosarcoma that has recurred after previous treatment might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that are sensitive to CYP3A4 or are moderate to strong inhibitors/inducers of CYP3A4 two weeks before starting the study and until two weeks after the last dose. Herbal supplements must be stopped at least 7 days before the first dose. Please consult with your doctor about your specific medications.

Is there any evidence suggesting that AZD1775 is likely to be safe for humans?

Research has shown that AZD1775, also known as adavosertib, has been tested in individuals with uterine cancer. Some studies suggest potential benefits, but safety concerns remain. For instance, one study found that the initial dose was too strong for some participants, leading to difficult side effects.

In other studies, AZD1775 demonstrated the ability to slow or stop cancer growth in certain cases. However, the safety of this treatment is still under investigation. As the current trial is in Phase 2, researchers continue to assess its safety and potential side effects.

Prospective trial participants should understand that while AZD1775 shows promise, researchers are still evaluating its safety. Consulting a doctor for personalized advice is crucial for those considering participation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for uterine cancer?

Researchers are excited about AZD1775 for uterine cancer because it takes a unique approach compared to standard treatments like chemotherapy and radiation. AZD1775 is an investigational drug that works by inhibiting a specific enzyme called Wee1, which plays a role in cell division. This unique mechanism targets cancer cells more precisely, potentially leading to fewer side effects than traditional therapies. Additionally, AZD1775 is taken orally in cycles, offering a more convenient administration compared to some intravenous options. This novel approach could offer new hope for patients with challenging cases like uterine serous carcinoma and carcinosarcoma.

What evidence suggests that AZD1775 might be an effective treatment for uterine cancer?

Research has shown that AZD1775, also known as adavosertib, holds early promise in treating uterine cancer, particularly uterine serous carcinoma. In earlier studies, adavosertib shrank tumors in about 26% of patients with this cancer type who had already tried several other treatments. This means roughly one in four patients experienced tumor reduction. However, while the drug demonstrated some effectiveness, it caused side effects at higher doses. Despite these issues, its ability to target a specific protein involved in cell division makes it a promising candidate for further research. Participants in this trial will receive AZD1775 in various contexts, including uterine serous carcinoma and carcinosarcoma, to further evaluate its effectiveness and safety. ^{1 2 3 4 5}

Who Is on the Research Team?

Joyce Liu, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for women aged 18+ with recurrent or persistent uterine serous carcinoma or carcinosarcoma, who've had one platinum-based chemo treatment. They must have measurable disease, normal organ/marrow function, and not be pregnant or breastfeeding. Participants need to agree to use contraception and can't join if they've recently had certain treatments, other cancers (with exceptions), severe heart conditions, uncontrolled illnesses, or are HIV-positive.

Inclusion Criteria

I am fully active or can carry out light work.

Women of child-bearing potential must use adequate contraception

My organs and bone marrow are functioning normally.

Exclusion Criteria

Receiving other investigational agents

History of allergic reactions to compounds similar to AZD1775

Pregnancy or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD1775 orally on days 1 through 5 and days 8 through 12 of each 21-day cycle

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• AZD1775

Trial Overview The study tests AZD1775 as a potential treatment for uterine cancer. It's an investigational drug given orally. The trial will assess its effectiveness in patients with specific genetic alterations (p53) and those who have previously undergone chemotherapy but whose cancer has returned.

How Is the Trial Designed?

Group I: Part C: AZD1775 in Uterine Serous with biopsiable disease Experimental Treatment 1 Intervention

-AZD1775 will be taken by mouth daily on days 1 through 5 and days 8 through 12 of each 21-day cycle

Group II: Part B: AZD1775 in Carcinosarcoma Experimental Treatment 1 Intervention

-AZD1775 will be taken by mouth daily on days 1 through 5 and days 8 through 12 of each 21-day cycle

Group III: Part A: AZD1775 Experimental Treatment 1 Intervention

-AZD1775 will be taken by mouth daily on days 1 through 5 and days 8 through 12 of each 21-day cycle

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

AZD1775, a WEE1 kinase inhibitor, was found to be safe and well-tolerated in a study involving 202 patients with refractory solid tumors, both as a monotherapy and in combination with chemotherapy.

The study showed that AZD1775 effectively engaged its target, leading to a 21% response rate in TP53-mutated patients, compared to 12% in those with wild-type TP53, suggesting it may be particularly beneficial for patients with TP53 deficiencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study Evaluating WEE1 Inhibitor AZD1775 As Monotherapy and in Combination With Gemcitabine, Cisplatin, or Carboplatin in Patients With Advanced Solid Tumors. Leijen, S., van Geel, RM., Pavlick, AC., et al.[2023]

In a phase 2 study involving 241 patients with advanced endometrial cancer, the combination of sapanisertib and paclitaxel showed a median progression-free survival (PFS) of 5.6 months compared to 3.7 months for paclitaxel alone, although the primary endpoint was not statistically significant (p = 0.139).

The combination treatment resulted in a higher rate of grade ≥ 3 treatment-emergent adverse events (89.5% for paclitaxel+sapanisertib vs. 54.0% for paclitaxel alone), indicating increased toxicity, but it was still considered manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer. Han, SN., Oza, A., Colombo, N., et al.[2023]

In a phase 2 study involving 44 patients with advanced or metastatic endometrial cancer who had limited treatment options, everolimus showed a 36% non-progressive disease rate at 3 months, indicating some efficacy in this difficult-to-treat population.

The most common side effects included anemia, fatigue, and hypercholesterolemia, but overall, everolimus was considered to have acceptable tolerability, supporting further research into targeted therapies for endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Everolimus as second- or third-line treatment of advanced endometrial cancer: ENDORAD, a phase II trial of GINECO. Ray-Coquard, I., Favier, L., Weber, B., et al.[2022]

Women with advanced or recurrent endometrial cancer have poor outcomes, with chemotherapy being the primary treatment despite low response rates; the combination of doxorubicin and cisplatin is the first-line choice but still yields low survival rates.

Topotecan shows promise as a treatment option, achieving a 10% response rate and stabilizing disease in 55% of previously treated patients, and is being studied in combination with cisplatin for chemotherapy-naive elderly patients, particularly for aggressive forms like uterine papillary serous carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment options for endometrial cancer: experience with topotecan. Holloway, RW.[2019]

Endometrial cancer has a better prognosis when detected early, but for recurrent or metastatic cases, the median survival is only about 12 months, highlighting the need for effective treatment options.

Recent trials show that combining doxorubicin, cisplatin, and paclitaxel significantly improves response rates and overall survival compared to the standard doxorubicin plus cisplatin regimen, suggesting a more effective approach for treating advanced endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in endometrial cancer. Obel, JC., Friberg, G., Fleming, GF.[2007]

Citations

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

ADAGIO: A Phase IIb, Open-Label, Single-Arm, Multicenter ... A phase II trial of the Wee1 inhibitor adavosertib (AZD1775) in recurrent uterine serous carcinoma. Joyce F. Liu et al. +0 authors. ORIGINAL ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40262070/

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 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03668340?cond=Carcinosarcoma&aggFilters=status:act&viewType=Table&rank=6

AZD1775 in Women With Recurrent or Persistent Uterine ... This study is being done to assess the safety and effectiveness of AZD1775 to learn if AZD1775 works in treating this type of cancer. Official Title. A Phase 2 ...

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. 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.