Berzosertib + Gemcitabine for Ovarian Cancer

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

70 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

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. ^{1 4 6 7 8}

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. ^{1 2 4 7 9}

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.

Research Team

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.

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.

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 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.

Participant Groups

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+

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

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]

References

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

Gemcitabine in ovarian cancer. [2022]

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

The current role of gemcitabine in ovarian cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Gemcitabine-oxaliplatin (GEMOX) as salvage treatment in pretreated epithelial ovarian cancer patients. [2022]

4. England pubmed.ncbi.nlm.nih.gov

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]

5. Singapore pubmed.ncbi.nlm.nih.gov

Complete remission of recurrent and refractory ovarian cancers using weekly administration of bevacizumab and gemcitabine/oxaliplatin: report of two cases. [2022]

6. England pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial. [2023]

8. Thailand pubmed.ncbi.nlm.nih.gov

Treatment outcomes of gemcitabine in refractory or recurrent epithelial ovarian cancer patients. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial. [2023]