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

49 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is studying an investigational drug as a possible treatment for uterine cancer. The drug involved in this study is: -AZD1775

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 AZD1775 safe for use in humans?

AZD1775 has been found to be safe and well-tolerated as a single treatment and in combination with chemotherapy in patients with advanced solid tumors. Common side effects include fatigue, nausea, vomiting, diarrhea, and blood-related issues, but the maximum-tolerated dose was not reached, indicating a favorable safety profile. ^{1 2 3 4 5}

How is the drug AZD1775 different from other treatments for uterine cancer?

AZD1775 is a unique treatment for uterine cancer as it targets specific pathways involved in cancer cell growth, potentially offering a novel approach compared to traditional chemotherapy options. While other treatments like ONC201 and topotecan focus on different mechanisms, AZD1775's distinct action may provide new hope for patients with limited options. ^{6 7 8 9 10}

Research Team

Joyce Liu, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

1. United States 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Anti-Tumor Effects of Wee1 Kinase Inhibitor with Radiotherapy in Human Cervical Cancer. [2021]

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

Phase II Study of WEE1 Inhibitor AZD1775 Plus Carboplatin in Patients With TP53-Mutated Ovarian Cancer Refractory or Resistant to First-Line Therapy Within 3 Months. [2021]

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

A phase II clinical trial of diaziquone in the treatment of patients with recurrent endometrial carcinoma. A Gynecologic Oncology Group study. [2019]

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

A phase II clinical trial of diaziquone (AZQ) in the treatment of patients with recurrent adenocarcinoma and adenosquamous carcinoma of the cervix. A Gynecologic Oncology Group study. [2019]

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

ONC201 demonstrates anti-tumorigenic and anti-metastatic activity in uterine serous carcinoma in vitro. [2022]

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

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

8. England pubmed.ncbi.nlm.nih.gov

Everolimus as second- or third-line treatment of advanced endometrial cancer: ENDORAD, a phase II trial of GINECO. [2022]

9. United States 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. [2023]

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

Chemotherapy in endometrial cancer. [2007]