Chemotherapy + Berzosertib for Ovarian Cancer

Not currently recruiting at 16 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors/inducers

Disqualifiers: Brain metastases, Li Fraumeni, others

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

Compensation: Varies

Number of Visits: 1

Duration: 21-day cycles, repeated until disease progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well a new drug, berzosertib, works with standard chemotherapy (carboplatin and gemcitabine hydrochloride) in treating certain types of recurrent and metastatic ovarian cancer. Researchers aim to determine the best dose and understand any side effects. This trial may suit individuals with specific types of ovarian, peritoneal, or fallopian tube cancer that respond to platinum-based treatments and have not previously received gemcitabine. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications to join the trial?

The trial protocol does not clearly specify if you need to stop your current medications. However, it mentions avoiding strong inhibitors or inducers of CYP3A4, a liver enzyme, as they may interact with the trial drugs. It's important to discuss your current medications with the trial team to ensure there are no interactions.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies found that the combination of berzosertib and gemcitabine was well tolerated by patients with advanced solid tumors. Berzosertib blocks certain enzymes necessary for cancer cell growth and showed promising safety results when combined with gemcitabine. Most patients managed the treatment well, experiencing only mild to moderate side effects.

Carboplatin, a common chemotherapy drug, has been used safely to treat ovarian cancer, even in frail, elderly patients. It is generally well-tolerated, with manageable side effects.

Gemcitabine, another chemotherapy drug for ovarian cancer, has been shown to be both effective and safe. It works well for patients whose cancer has returned, with a good safety profile.

Overall, research has shown that these drugs can be used safely together. While side effects can occur, they are usually not severe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about berzosertib for ovarian cancer because it offers a novel approach to treatment by targeting the ATR kinase, a crucial part of the DNA damage response pathway. Unlike standard options like carboplatin and gemcitabine alone, which primarily attack cancer cells directly, berzosertib enhances the effectiveness of these chemotherapy agents by preventing cancer cells from repairing their damaged DNA. This combination could potentially lead to better outcomes by making the cancer cells more vulnerable and less capable of survival after chemotherapy.

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

In this trial, participants will receive a combination of carboplatin, gemcitabine hydrochloride, and berzosertib. Research has shown that adding berzosertib to gemcitabine helps patients live longer without their cancer worsening. One study found that patients who took both berzosertib and gemcitabine had a median time of 22.9 weeks before their cancer progressed, compared to 14.7 weeks for those who took only gemcitabine. This suggests that berzosertib may enhance the effects of chemotherapy by blocking enzymes that cancer cells need to grow. Patients with advanced solid tumors have generally tolerated this combination well and have shown early signs of improvement. These findings are encouraging for those with recurrent ovarian, primary peritoneal, or fallopian tube cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Andrea E. Wahner Hendrickson, M.D.

Principal Investigator

Mayo Clinic Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with high-grade serous or endometrioid ovarian, peritoneal, or fallopian tube cancer that's metastatic and beyond cure. Participants must have measurable disease, be in their first or second platinum-sensitive recurrence (recurrence >6 months after last platinum therapy), and have adequate organ function. They can't join if they've had more than two prior platinum treatments, recent chemotherapy/radiotherapy, known brain metastases, allergies to the drugs being tested, are pregnant/breastfeeding, or have certain genetic syndromes.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

My cancer is a specific type that has spread and cannot be cured with surgery or radiation.

I have a tumor that can be measured with scans or exams.

Exclusion Criteria

I will not receive bevacizumab as part of this study's treatment.

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

My cancer did not respond to platinum-based treatment or it came back after such treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation/Safety Lead-in

Assess safety and tolerability of the combination therapy and determine the dose for the expansion cohort

Up to 28 days

Multiple visits for dose escalation and monitoring

Treatment

Patients receive carboplatin, gemcitabine hydrochloride, and berzosertib in 21-day cycles

21-day cycles, repeated until disease progression or unacceptable toxicity

IV administration on days 1, 2, 8, and 9 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Berzosertib
• Carboplatin
• Gemcitabine Hydrochloride

Trial Overview The trial tests how well patients respond to a combination of Carboplatin and Gemcitabine Hydrochloride with Berzosertib versus standard treatment alone. It aims to find the best dose of these drugs together while assessing side effects when treating recurrent/metastatic ovarian, primary peritoneal or fallopian tube cancer.

How Is the Trial Designed?

Group I: Treatment (carboplatin, gemcitabine hydrochloride, VX-970) Experimental Treatment 5 Interventions

Patients receive carboplatin IV over 30 minutes on day 1, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and berzosertib IV over 60 minutes on days 2 and 9. 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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11095660/

Randomized Phase II Study of Gemcitabine With or Without ... Addition of ATR inhibitor (ATRi) berzosertib to gemcitabine increased progression-free survival (PFS) compared to gemcitabine alone.

2. sciencedirect.com sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/berzosertib

Berzosertib - an overview Berzosertib is the first ATR inhibitor to be evaluated in humans, with the first participant enrolled in a clinical study on December 10, 2012.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.5512

Randomized phase 2 study of gemcitabine with or without ... Addition of ATR inhibitor (ATRi) berzosertib to gemcitabine increased progression-free survival (PFS) compared to gemcitabine alone.

4. nature.com nature.com/articles/s41416-021-01405-x

Phase 1 study of the ATR inhibitor berzosertib (formerly ... Berzosertib + gemcitabine was well tolerated in patients with advanced solid tumours and showed preliminary efficacy signs.

5. healio.com healio.com/news/hematology-oncology/20200706/berzosertib-regimen-extends-pfs-in-ovarian-cancer-subset

Berzosertib regimen extends PFS in ovarian cancer subset Results showed median PFS of 22.9 weeks (90% CI, 17.9-72) in the combination group and 14.7 weeks (90% CI, 9.7-36.7) for the gemcitabine ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12278758/

Safety and Tolerability of Berzosertib, an Ataxia ... The addition of ATR inhibition to PARP inhibition results in mitotic lethality and an opportunity to further enhance cisplatin sensitivity.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9740197/

ATR Inhibitors in Platinum-Resistant Ovarian Cancer - PMC Multiple Phase I trials showed that the recommended phase II dose (RP2D) of berzosertib was 210 mg/m2 with intermittent use of other drugs [76,77,78].

8. sciencedirect.com sciencedirect.com/science/article/pii/S0169500221006048

Lung Cancer Berzosertib plus gemcitabine was well tolerated in patients with advanced, pre-treated NSCLC. Based on the observed clinical efficacy, future clinical trials ...

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)60417-5/fulltext

Randomized phase II (RP2) study of ATR inhibitor M6620 ... Primary endpoint was progression-free survival (PFS) while secondary endpoints included safety, objective response and clinical benefit rate. Unlimited prior ...