Berzosertib + Gemcitabine for Ovarian Cancer

Not currently recruiting at 19 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors/inducers, Antiretrovirals

Disqualifiers: Brain metastases, Uncontrolled illness, Pregnancy, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 31

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining a new drug, ATR kinase inhibitor M6620, with the chemotherapy drug gemcitabine (Gemzar) is more effective than using gemcitabine alone for certain recurrent ovarian cancers. The focus is on ovarian, primary peritoneal, or fallopian tube cancers that have returned after initial improvement. Patients with these cancers, who have shown resistance to platinum-based treatments within six months, might be suitable candidates. The goal is to determine if the new combination can more effectively stop cancer cell growth compared to the standard treatment. 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 protocol does not specify if you must stop taking your current medications. However, you should avoid medications that strongly affect the CYP3A4 enzyme, as they may interact with the trial drugs. It's important to discuss your current medications with the trial team to ensure safety.

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

Research shows that the combination of berzosertib and gemcitabine is generally well-tolerated by patients with advanced cancers. Studies have found that this combination has been safely used in patients with advanced solid tumors, such as lung cancer, without unexpected side effects.

Gemcitabine alone, a chemotherapy drug, treats ovarian cancer and is known for its good safety record. Serious side effects are uncommon, making it a standard part of cancer treatment.

Overall, evidence suggests that the combination of berzosertib and gemcitabine is safe, with both treatments well-tolerated in previous patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about berzosertib combined with gemcitabine for ovarian cancer because it targets cancer cells differently than standard treatments. Most ovarian cancer therapies focus on killing rapidly dividing cells, but berzosertib is an ATR kinase inhibitor, which disrupts the cancer cells' ability to repair their DNA. This mechanism could potentially make it more effective against tumors that have become resistant to conventional chemotherapy. Additionally, combining berzosertib with gemcitabine may enhance the effectiveness of treatment by exploiting the weaknesses in cancer cells' DNA repair processes, offering hope for improved outcomes.

What evidence suggests that this trial's treatments could be effective for ovarian cancer?

In this trial, participants will be assigned to one of two treatment arms. Arm I involves treatment with gemcitabine alone, which has already shown promise, with nearly 20% of patients experiencing cancer remission. Arm II involves a combination of gemcitabine and the drug M6620. Research has shown that adding M6620 to gemcitabine can make treatment for recurring ovarian cancer more effective. Specifically, studies have found that this combination helps patients live longer without their cancer worsening, averaging about 22.9 weeks compared to 14.7 weeks with just gemcitabine. M6620 may enhance gemcitabine's effectiveness by blocking an enzyme that cancer cells need to grow. Overall, these findings suggest that the combination could outperform gemcitabine alone. ^{4 5 6 7 8}

Who Is on the Research Team?

Panagiotis A Konstantinopoulos

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for patients with high-grade serous ovarian, primary peritoneal, or fallopian tube cancer that's resistant to platinum-based treatment and has recurred. Participants must have measurable disease, resolved prior therapy side effects (except hair loss), good physical health, and adequate organ function. They can't join if they've had certain recent treatments, brain metastases, uncontrolled illnesses, are pregnant/breastfeeding or HIV-positive on antiretrovirals.

Inclusion Criteria

I am not allergic to the study drugs M6620 or gemcitabine.

Ability to understand and the willingness to sign a written informed consent document

My kidney function is normal or nearly normal.

Exclusion Criteria

I am allergic to medications similar to M6620 or gemcitabine.

My cancer got worse during my first platinum-based chemotherapy.

I have undergone radiotherapy in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive gemcitabine hydrochloride with or without ATR kinase inhibitor M6620 in 21-day cycles

Up to 3 years

Visits 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

Follow-up at 30 days, every 3 months for 1 year, then every 6 months for 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• M6620

Trial Overview The study compares the effectiveness of adding ATR kinase inhibitor M6620 (Berzosertib) to gemcitabine hydrochloride versus using gemcitabine alone in recurrent cancers. M6620 potentially enhances cell growth inhibition by blocking a key enzyme and may improve gemcitabine's efficacy.

How Is the Trial Designed?

Group I: Arm II (gemcitabine, ATR kinase inhibitor M6620) Experimental Treatment 3 Interventions

Patients receive gemcitabine hydrochloride as in Arm I and ATR kinase inhibitor M6620 IV over 60-90 minutes on days 2 and 9. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (gemcitabine hydrochloride) Active Control 2 Interventions

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover to Arm II.

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Gemcitabine (GEMZAR) has shown to be an effective treatment for non-small-cell lung cancer (NSCLC) with a response rate of about 21% as a single agent, and it has a mild toxicity profile, making it suitable for combination therapies.

When combined with cisplatin, gemcitabine achieved higher response rates ranging from 38% to 54% and median survival times of 8.4 to 14.3 months, with manageable side effects, indicating its potential as a preferred treatment option in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination studies with gemcitabine in the treatment of non-small-cell lung cancer. Steward, WP.[2022]

Gemcitabine has shown promising results as a single-agent treatment for platinum-resistant ovarian cancer, achieving remission rates of nearly 20% with a favorable safety profile.

Combining gemcitabine with carboplatin has been explored in phase I and II trials, showing potential for improved efficacy in treating ovarian cancer, and further combinations with other agents are being actively researched.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in ovarian cancer. Orlando, M., Mandachain, M.[2022]

In a study of 43 recurrent epithelial ovarian cancer patients treated with gemcitabine, the overall response rate was modest at 11.6%, with better outcomes in platinum-sensitive patients (19% response) compared to platinum-resistant patients (4.5%).

Combining gemcitabine with platinum-based chemotherapy significantly improved progression-free survival (PFS) to 8.1 months compared to 2.7 months with gemcitabine alone in platinum-sensitive patients, indicating that combination therapy may enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment outcomes of gemcitabine in refractory or recurrent epithelial ovarian cancer patients. Chanpanitkitchot, S., Tangjitgamol, S., Khunnarong, J., et al.[2022]

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/science/article/abs/pii/S1470204520301807

Articles Berzosertib plus gemcitabine versus ... Median progression-free survival was 22·9 weeks (17·9–72·0) for gemcitabine plus berzosertib and 14·7 weeks (90% CI 9·7–36·7) for gemcitabine alone (hazard ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02595892?id=%22NCT00183794%22OR%22NCT00312650%22OR%22NCT01936974%22OR%22NCT02272790%22OR%22NCT02595892%22OR%22NCT03598270%22OR%22NCT03690739%22&rank=3&tab=results

Gemcitabine Hydrochloride Alone or With M6620 in ... Patients receive gemcitabine hydrochloride as in Arm I and ATR kinase inhibitor M6620 IV over 60-90 minutes on days 2 and 9. Cycles repeat every 21 days in the ...

4. withpower.com withpower.com/trial/berzosertib-gemcitabine-for-ovarian-cancer-045bd

Berzosertib + Gemcitabine for Ovarian Cancer Gemcitabine has shown promising results as a single-agent treatment for platinum-resistant ovarian cancer, achieving remission rates of nearly 20% with a ...

5. nature.com nature.com/articles/s41467-021-25904-w

A Replication stress biomarker is associated with response ... Here we report a candidate biomarker of response to gemcitabine versus combined gemcitabine and ATR inhibitor therapy in HGSOC ovarian cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8023719/

Berzosertib plus gemcitabine versus ... - PubMed Central Median progression-free survival was 22·9 weeks (17·9–72·0) for gemcitabine plus berzosertib and 14·7 weeks (90% CI 9·7–36·7) for gemcitabine alone (hazard ...

7. 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 ...

8. 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.