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Ovarian Serous TumorPhase 2NCT02595892

Gemcitabine Hydrochloride Alone or With M6620 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

A Phase 2 study testing Berzosertib, Gemcitabine and Gemcitabine Hydrochloride in people with Ovarian Serous Tumor and Recurrent Fallopian Tube Carcinoma, run by National Cancer Institute (NCI) at 17 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Berzosertib, Gemcitabine and Gemcitabine Hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
17 sitesUnited States
Study dates
25 Aug 2016to 5 Aug 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically confirmed high grade serous ovarian or primary peritoneal or fallopian tube cancer; platinum resistant disease is defined as progression within 6 months after last platinum regimen
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam; measurable disease by RECIST version (v)1.1 with at least one measurable target lesion
  • Prior therapy: No line limit but no more than 1 prior regimens in the platinum resistant setting; no prior treatment targeting the ATR/checkpoint kinase 1 (CHK1) pathway and no prior gemcitabine as single agent; hormonal therapies immunotherapy, and antiangiogenic therapies (as single agents) do not count as lines; poly (adenosine diphosphate [ADP]-ribose) polymerases (PARP)-inhibitors count as a line of therapy unless given in the maintenance setting; PARP-inhibitors given as maintenance after platinum therapy do not count as a line of therapy; prior carboplatin/gemcitabine is allowed provided that there was no disease progression within 12 months after completion of the carboplatin/gemcitabine regimen; subjects may begin protocol treatment at least 4 weeks or 5 half-lives, whichever is shorter, after their last dose of chemotherapy or hormonal therapy, assuming they are otherwise eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky >= 70%)
  • Life expectancy of greater than 6 months
  • Leukocytes >= 3,000/mcL (within 2 weeks prior to initiation of study treatment)
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  • Absolute neutrophil count >= 1,500/mcL (within 2 weeks prior to initiation of study treatment)
  • Platelets >= 100,000/mcL (within 2 weeks prior to initiation of study treatment)
  • Total bilirubin within normal institutional limits (within 2 weeks prior to initiation of study treatment)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (within 2 weeks prior to initiation of study treatment)
  • Creatinine =< upper limit of institutional normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (within 2 weeks prior to initiation of study treatment)
  • Confirmation of availability of a formalin-fixed, paraffin-embedded (FFPE) tumor specimen with adequate tumor tissue (either one paraffin embedded tissue block OR 10 5-micron unstained slides from the block on regular [non-plus] slides and 1 hematoxylin and eosin [H\&E] slide)
  • All acute, clinically significant treatment-related toxicity from prior therapy, except for alopecia, must have resolved to grade =< 1 prior to study entry
  • At least 4 weeks since major surgery or radiation therapy
  • The effects of M6620 (VX-970) on the developing human fetus are unknown; for this reason and because deoxyribonucleic acid (DNA) damage inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 6 months after completion of study; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • No known hypersensitivity or contraindication to the components of study treatment (M6620 [VX-970], gemcitabine)
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients with primary platinum refractory disease, defined as progression while first line platinum based chemotherapy
  • Patients who have had chemotherapy within 4 weeks or five half-lives, whichever is shorter, (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who have had radiotherapy within 4 weeks
  • Patients who are receiving any other investigational agents
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; a scan to confirm the absence of brain metastasis is not required
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to M6620 (VX-970) or gemcitabine
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  • M6620 (VX-970) is primarily metabolized by CYP3A4; therefore concomitant administration with strong inhibitors or inducers of CYP3A4 should be avoided; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of; patients receiving any medications or substances that are inhibitors or inducers of cytochrome P450 3A (CYP3A4 enzyme) are ineligible; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because M6620 (VX-970) and/or gemcitabine are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M6620 (VX-970) and/or gemcitabine, breastfeeding should be discontinued if the mother is treated with M6620 (VX-970) and/or gemcitabine
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with M6620 (VX-970) and/or gemcitabine; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • UC San Diego Medical Center - Hillcrest

    San Diego, California, 92103

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: Phase 2 Study of M6620 (VX-970) in Combination With Gemcitabine Versus Gemcitabine Alone in Subjects With Platinum-Resistant Recurrent Ovarian or Primary Peritoneal Fallopian Tube Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Assess and compare progression free survival (PFS) between gemcitabine (gemcitabine hydrochloride)/M6620 (VX-970) and gemcitabine alone arms.

SECONDARY OBJECTIVES:

  1. Determine and compare overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) between gemcitabine/M6620 (VX-970) and gemcitabine alone arms.

II. Determine and compare the safety profile of gemcitabine/M6620 (VX-970) and gemcitabine alone regimens.

III. Assess and compare PFS at 6 months between gemcitabine/M6620 (VX-970) and gemcitabine alone arms.

IV. Determine and compare the clinical benefit rate (CBR) between gemcitabine/M6620 (VX-970) and gemcitabine alone arms.

  1. Determine and compare the duration of response (DOR) between gemcitabine/M6620 (VX-970) and gemcitabine alone arms.

VI. Determine and compare cancer antigen (CA)125 reduction by >= 50% between gemcitabine/M6620 (VX-970) and gemcitabine alone arms.

VII. Determine and compare overall survival (OS) between gemcitabine/M6620 (VX-970) and gemcitabine alone arms.

VIII. Determine the ORR for subjects in the gemcitabine alone arm who cross over to the gemcitabine/M6620 (VX-970) arm.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive gemcitabine hydrochloride intravenously (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.

ARM II: 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.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, and then every 6 months for 2 years.

Being tested
Berzosertib, Gemcitabine, Gemcitabine Hydrochloride
Medical subject headings
Fallopian Tube Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BerzosertibDrug

    Also called 2-Pyrazinamine, 3-(3-(4-((Methylamino)methyl)phenyl)-5-isoxazolyl)-5-(4-((1-methylethyl)sulfonyl)phenyl)-, M 6620, M6620, VX 970

    Given IV

  • GemcitabineDrug

    Also called dFdC, dFdCyd, Difluorodeoxycytidine

    Given IV

  • Gemcitabine HydrochlorideDrug

    Also called dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, Gemzar

    Given IV

Study groups in NCT02595892
Study groupRoleWhat they receive
Arm I (gemcitabine hydrochloride)Active comparatorPatients 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.
Receives: Drug: Gemcitabine; Drug: Gemcitabine Hydrochloride
Arm II (gemcitabine, ATR kinase inhibitor M6620)ExperimentalPatients 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.
Receives: Drug: Berzosertib; Drug: Gemcitabine; Drug: Gemcitabine Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS)

    PFS was summarized using Kaplan-Meier analyses and compared between the two arms using the logrank test. Additionally, PFS was analyzed using a Cox Proportional Hazards Model, including the stratification factor, and will be used to estimate the hazard ratio of the gemcitabine hydrochloride (gemcitabine)/ataxia telangiectasia mutated and Rad3-related (ATR) kinase inhibitor M6620 (formerly VX-970) arm relative to the gemcitabine alone arm and the associated 90% confidence interval. Disease progression, per protocol, is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the diameters of target lesions, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

    Measured: Number of days from the day the subject received the first dose of protocol therapy to the date of documented progressive disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or death (regardless of cause), assessed up to 3 years

Secondary outcomes (8)

  1. Objective Response Rate (ORR)

    Defined as the percentage of subjects achieving a response rating of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) in the whole population. Per RECIST v1.1 definitions for target lesions and assessed by conventional CT and MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the diameters of target lesions; Overall Response (OR) = CR + PR. ORR was summarized by counts (percentages) in each Arm.

    Measured: Up to 3 years

  2. Progression Free Survival at 6 Months (PFS-6)

    Assessed and compared PFS-6 between gemcitabine/VX-970 and gemcitabine alone arms

    Measured: Number of days from the day the subject received the first dose of protocol therapy to the date of documented progressive disease by RECIST version 1.1 or death (regardless of cause), assessed at 6 months

  3. Clinical Benefit Rate (CBR)

    CBR is defined as the percentage of subjects achieving a response rating of stable disease >= 4 months, partial response (PR), or complete response (CR). Subject demographic and baseline characteristics will be summarized by mean, standard deviation, median, minimum, and maximum for continuous variables; and by counts and percentages for categorical variables. Summaries will be provided separately for each treatment group. Treatment group comparisons in CBR will be evaluated using logistic regression and expressed as odds ratios with associated 90% confidence intervals. In the event that rates are low, comparisons will be based on Fisher's exact test.

    Measured: Up to 3 years

  4. Objective Response Rate by Platinum Free Status

    Objective response rate by platinum-free status includes only informational summaries (counts of participants who met the categories outlined below) without formal statistical comparisons.

    Measured: Up to 3 years

  5. Percentage of Patients With a Reduction in CA-125

    Determined and compared CA125 reduction by > 50% between gemcitabine/VX-970 and gemcitabine alone arms.

    Measured: CA-125 serum samples were collected from participants in both Arms I and II at baseline, on Day 1 of each cycle, and at the end-of-study treatment visit, assessed up to 2 years.

  6. Overall Survival (OS)

    Assessed and compared OS between gemcitabine/VX-970 and gemcitabine alone arms.

    Measured: Number of weeks from the date of registration until date of death (regardless of cause), assessed up to 3 years.

  7. Number of Participants With Serious Adverse Events (SAEs)

    Determined and compared the safety profile of gemcitabine/VX-970 and gemcitabine alone regimens.

    Measured: AE checks occurred on D1 and D8 of each cycle for up to 2 years and at the Final Treatment Visit. Patients who were removed from study treatment for unacceptable AEs were followed until resolution/stabilization of the AE up to 3 years, or until death.

  8. Duration of Response

    Duration of response was evaluated at the first instance of CR or PR through the earliest assessment of progressive disease, death, or the last follow-up where the subject had not yet progressed from her prior response. Informational summaries without formal statistical comparisons were produced.

    Measured: Assessed for up to 3 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 2015 (estimated)
  2. Study start25 Aug 2016
  3. Primary completion15 Jun 2020
  4. Study completion5 Aug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02595892
Sponsor's protocol ID
NCI-2015-01910
Other IDs
NCI-2015-01910, 16-724, 9944, 9944, UM1CA186709
Status last verified
Aug 2026
First submitted
3 Nov 2015
Last updated
9 Sep 2026
Data monitoring committee
No

Publications

  • Konstantinopoulos PA, Cheng SC, Lee EK, da Costa AABA, Gulhan D, Wahner Hendrickson AE, Kochupurakkal B, Kolin DL, Kohn EC, Liu JF, Penson RT, Stover EH, Curtis J, Sawyer H, Polak M, Chowdhury D, D'Andrea AD, Farkkila A, Shapiro GI, Matulonis UA. Randomized Phase II Study of Gemcitabine With or Without ATR Inhibitor Berzosertib in Platinum-Resistant Ovarian Cancer: Final Overall Survival and Biomarker Analyses. JCO Precis Oncol. 2024 Apr;8:e2300635. doi: 10.1200/PO.23.00635.

    PubMed 38635934

  • Konstantinopoulos PA, Cheng SC, Wahner Hendrickson AE, Penson RT, Schumer ST, Doyle LA, Lee EK, Kohn EC, Duska LR, Crispens MA, Olawaiye AB, Winer IS, Barroilhet LM, Fu S, McHale MT, Schilder RJ, Farkkila A, Chowdhury D, Curtis J, Quinn RS, Bowes B, D'Andrea AD, Shapiro GI, Matulonis UA. Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2020 Jul;21(7):957-968. doi: 10.1016/S1470-2045(20)30180-7. Epub 2020 Jun 15.

    PubMed 32553118

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Berzosertib, Gemcitabine and Gemcitabine Hydrochloride in people with Ovarian Serous Tumor and Recurrent Fallopian Tube Carcinoma, run by National Cancer Institute (NCI) at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: Number of days from the day the subject received the first dose of protocol therapy to the date of documented progressive disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or death (regardless of cause), assessed up to 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02595892, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2026.

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