70 Participants Needed

Berzosertib + Gemcitabine for Ovarian Cancer

Recruiting at 19 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 4 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This randomized phase II trial studies how well ATR kinase inhibitor M6620 (M6620) and gemcitabine hydrochloride work compared to standard treatment with gemcitabine hydrochloride alone in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of improvement (recurrent). ATR kinase inhibitor M6620 may stop the growth of tumor cells by blocking an enzyme needed for cell growth, and may also help gemcitabine hydrochloride work better. Gemcitabine hydrochloride is a drug used in chemotherapy that works to stop the growth of tumor cells by blocking cells from growing and repairing themselves, causing them to die. It is not yet known whether adding ATR kinase inhibitor M6620 to standard treatment with gemcitabine hydrochloride is more effective than gemcitabine hydrochloride alone in treating patients with ovarian, primary peritoneal, or fallopian tube cancer.

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.

What data supports the effectiveness of the drug combination Berzosertib + Gemcitabine for ovarian cancer?

Gemcitabine has shown consistent activity in treating platinum-resistant ovarian cancer, with remission rates of nearly 20% and a favorable safety profile. It has been effectively combined with other drugs like carboplatin and oxaliplatin in clinical trials, suggesting potential benefits when used in combination therapies for ovarian cancer.12345

Is the combination of Berzosertib and Gemcitabine safe for treating ovarian cancer?

The combination of Berzosertib and Gemcitabine has been studied for high-grade serous ovarian cancer and showed acceptable safety levels. Gemcitabine alone has a favorable safety profile, with mild side effects like short-lived blood cell count reductions.14678

What makes the drug combination of berzosertib and gemcitabine unique for treating ovarian cancer?

The combination of berzosertib and gemcitabine is unique because berzosertib is a selective ATR inhibitor that targets the increased replication stress in high-grade serous ovarian cancer, potentially making it more effective than gemcitabine alone.12479

Research Team

PA

Panagiotis A Konstantinopoulos

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

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.
See 14 more

Exclusion Criteria

I am allergic to medications similar to M6620 or gemcitabine.
My cancer got worse during my first platinum-based chemotherapy.
I do not have any serious illnesses or social situations that would stop me from following the study's requirements.
See 7 more

Timeline

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

Treatment Details

Interventions

  • Gemcitabine
  • M6620
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm II (gemcitabine, ATR kinase inhibitor M6620)Experimental Treatment3 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 Control2 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

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

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.
Gemcitabine in ovarian cancer.Orlando, M., Mandachain, M.[2022]
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.
Combination studies with gemcitabine in the treatment of non-small-cell lung cancer.Steward, WP.[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.
Treatment outcomes of gemcitabine in refractory or recurrent epithelial ovarian cancer patients.Chanpanitkitchot, S., Tangjitgamol, S., Khunnarong, J., et al.[2022]

References

Gemcitabine in ovarian cancer. [2022]
The current role of gemcitabine in ovarian cancer. [2022]
Gemcitabine-oxaliplatin (GEMOX) as salvage treatment in pretreated epithelial ovarian cancer patients. [2022]
A phase II study of the combination chemotherapy of bevacizumab and gemcitabine in women with platinum-resistant recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. [2022]
Complete remission of recurrent and refractory ovarian cancers using weekly administration of bevacizumab and gemcitabine/oxaliplatin: report of two cases. [2022]
Combination studies with gemcitabine in the treatment of non-small-cell lung cancer. [2022]
Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial. [2023]
Treatment outcomes of gemcitabine in refractory or recurrent epithelial ovarian cancer patients. [2022]
Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial. [2023]