Carboplatin, Gemcitabine Hydrochloride, and Berzosertib in Treating Patients With Recurrent and Metastatic Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

NCT02627443 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 7 other identifiers: NCI-2015-02064MC15639948N01CM00099P30CA015083UM1CA186686UM1CA186709
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 14

Brief Summary

This phase I trial studies the side effects and best dose of gemcitabine hydrochloride and berzosertib when given together with carboplatin in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back (recurrent) and has spread to other places in the body (metastatic). Chemotherapy drugs, such as carboplatin and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Berzosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving berzosertib with chemotherapy (carboplatin and gemcitabine hydrochloride) may work better in treating patients with ovarian, primary peritoneal, or fallopian tube cancer compared to chemotherapy alone.

Conditions

Ovarian Endometrioid Tumor; Platinum-Sensitive Ovarian Carcinoma; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Ovarian High Grade Serous Adenocarcinoma; Recurrent Primary Peritoneal Carcinoma; Metastatic Primary Peritoneal Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7; Metastatic Ovarian Carcinoma; Metastatic Fallopian Tube Carcinoma

Outcome Measures

Primary Outcomes (2)

• Dost Limiting Toxicity (DLT) (Phase I Dose Escalation)

  DLT will be defined as grade 4 absolute neutrophil count for ≥ 5 days, grade 4 anemia, platelet count \< 25,000, or other non-hematologic events ≥ grade 3 as per NCI Common Terminology Criteria for Adverse Events Version 4.0 (except fatigue, alopecia and anorexia). The MTD in this study will be defined as the highest safely tolerated dose, up to a maximum of dose level 4, where at most 1 out of six patients experience a DLT with the next higher dose having at least 2 DLTs in 3 or more patients.

  Up to 28 days

• Incidence of Adverse Events

  The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Up to 3 years

Secondary Outcomes (4)

• Confirmed Response Rate

  Up to 3 years

• Overall Survival (OS)

  From study entry to death from any cause, assessed up to 3 years

• Duration of Response

  From first documented date of confirmed response (complete response [CR] or partial response [PR]), to the date at which progression is first documented, up to 3 years

• Progression Free Survival (PFS)

  From registration to the first of either disease progression or death from any cause, up to 3 years

Other Outcomes (2)

• Changes in the Frequency of Marker Inhibition

  Baseline to up to 3 years

• Correlation Between Deoxyribonucleic Acid (DNA) Damage Markers and Mutation Data With Clinical Endpoints (i.e. Response, PFS, OS)

  Up to 3 years

Study Arms (1)

Treatment (carboplatin, gemcitabine hydrochloride, VX-970)

EXPERIMENTAL

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.

Drug: Berzosertib; Drug: Carboplatin; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (carboplatin, gemcitabine hydrochloride, VX-970)

Pharmacological Study OTHER

Correlative studies

Treatment (carboplatin, gemcitabine hydrochloride, VX-970)

Berzosertib DRUG

Given IV

Also known as: 2-Pyrazinamine, 3-(3-(4-((Methylamino)methyl)phenyl)-5-isoxazolyl)-5-(4-((1-methylethyl)sulfonyl)phenyl)-, M 6620, M6620, VX 970, VX-970, VX970

Treatment (carboplatin, gemcitabine hydrochloride, VX-970)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (carboplatin, gemcitabine hydrochloride, VX-970)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, Gemzar, LY 188011, LY-188011, LY188011

Treatment (carboplatin, gemcitabine hydrochloride, VX-970)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed high grade serous or endometrioid ovarian, peritoneal or fallopian tube malignancy that is metastatic and for which curative measures do not exist. The histology can be confirmed from tissue that was taken at the time of diagnosis. A biopsy at the time of recurrence prior to enrollment on study is not required
• 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
• Patients enrolled in the expansion cohort will be required to have archival tumor tissue available for analysis and be willing to have a tumor biopsy at baseline (after registration and prior to starting study treatment), at cycle 1 day 2 and at cycle 2 day 2. Patients must have platinum sensitive disease and be in their first or second platinum sensitive recurrence. Platinum sensitive disease is defined as recurrence that occurred greater than six months after completion of their last line of platinum based therapy. No non-platinum regimens allowed; prior therapy with PARP inhibitors as well as bevacizumab is allowed
• No more than two prior platinum based regimens. One regimen is defined as the interval of treatment from start of platinum based doublet to finish of that treatment course for the initial therapy or for the recurrent disease episode. If the nonplatinum agent is altered due to any reason other than disease progression, it counts as one regimen. For example, if a patient started on carboplatin and paclitaxel but developed a taxol reaction and was switched to carboplatin and Abraxane, this counts as one prior regimen
• Children are excluded from this study, but will be eligible for future pediatric trials
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 6 months
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count (ANC) \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2 x institutional upper limit of normal (ULN)
• Creatinine within normal institutional limits OR creatinine clearance \>= 50 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Negative serum pregnancy test result for females of child bearing potential
• Note: The effects of M6620 (VX-970) on the developing human fetus are unknown. For this reason and because deoxyribonucleic acid (DNA)-damage response (DDR) inhibitors as well as other therapeutic agents used in this trial may have teratogenic potential, 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 M6620 (VX-970) administration. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately

You may not qualify if:

• Patients with platinum resistant disease or platinum sensitive disease that is past the first or second recurrence
• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier, excluding alopecia. Patients with treatment related effects, such as peripheral neuropathy, that are grade 1 or less are eligible
• Prior exposure to gemcitabine
• 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
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to M6620 (VX-970), carboplatin, gemcitabine or to these specific compounds
• 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. 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) as a DNA-damage response (DDR) inhibitor may have 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), breastfeeding should be discontinued if the mother is treated with M6620 (VX-970). These potential risks also apply to the other agents used in this study, such as carboplatin and gemcitabine
• Patients with Li Fraumeni syndrome are excluded from the study as M6620 (VX-970) is a DDR inhibitor
• Addition of bevacizumab to the treatment in this study is not allowed; if the treating physician feels that the addition of bevacizumab is in the best interest of the patient, the patient should be treated with an FDA approved regimen outside of the present study

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (14)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

UF Health Cancer Institute - Gainesville

Gainesville, Florida, 32610, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

berzosertib; Carboplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Andrea Wahner Hendrickson
• Organization: Mayo Clinic

wahnerhendrickson.andrea@mayo.edu

(507) 284-2511

Study Officials

• Andrea E Wahner Hendrickson

  Mayo Clinic Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2015
• First Posted: December 11, 2015
• Study Start: May 16, 2017
• Primary Completion: October 4, 2024
• Study Completion (Estimated): June 3, 2026
• Last Updated: April 13, 2026
• Results First Posted: April 2, 2026

Record last verified: 2025-12

Locations

US (14)