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Carboplatin and Gemcitabine Hydrochloride With or Without ATR Kinase Inhibitor VX-970 in Treating Patients With Recurrent and Metastatic Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

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ClinicalTrials.gov Identifier: NCT02627443
Recruitment Status : Suspended (Scheduled Interim Monitoring)
First Posted : December 11, 2015
Last Update Posted : May 14, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This randomized phase I/II trial studies the side effects and how well carboplatin and gemcitabine hydrochloride with or without ATR kinase inhibitor VX-970 work 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). Drugs used in chemotherapy, 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. ATR kinase inhibitor VX-970 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving carboplatin and gemcitabine with or without ATR kinase inhibitor VX-970 may work better in treating ovarian, primary peritoneal, or fallopian tube cancer.

Condition or disease Intervention/treatment Phase
High Grade Ovarian Serous Adenocarcinoma Ovarian Endometrioid Tumor Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Stage IV Fallopian Tube Cancer AJCC v6 and v7 Stage IV Ovarian Cancer AJCC v6 and v7 Stage IV Primary Peritoneal Cancer AJCC v7 Drug: ATR Kinase Inhibitor M6620 Drug: Carboplatin Drug: Gemcitabine Hydrochloride Other: Laboratory Biomarker Analysis Other: Pharmacological Study Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 111 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Dose Escalation and Randomized Phase 2 Trial of Carboplatin and Gemcitabine With or Without M6620 (VX-970) in First Recurrence Platinum-Sensitive Epithelial Ovarian, Peritoneal, and Fallopian Tube Cancer
Actual Study Start Date : November 4, 2016
Estimated Primary Completion Date : November 30, 2020
Estimated Study Completion Date : November 30, 2020


Arm Intervention/treatment
Experimental: Arm I (carboplatin, gemcitabine hydrochloride, VX-970)
Patients receive carboplatin IV over 30 minutes on day 1, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and ATR kinase inhibitor VX-970 IV over 60 minutes on days 2 and 9. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: ATR Kinase Inhibitor M6620
Given IV
Other Names:
  • M 6620
  • M6620
  • VX-970

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

Active Comparator: Arm II (carboplatin, gemcitabine hydrochloride)
Patients receive carboplatin IV over 30 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies




Primary Outcome Measures :
  1. Confirmed response rate [ Time Frame: Up to 3 years ]
    Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. The proportion of patients with a confirmed response will be calculated and compared between the 2 treatment groups using a Chi-square or Fisher's Exact test.


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Time from study entry to death from any cause, assessed up to 3 years ]
    OS will be estimated using the Kaplan-Meier method, and the log-rank test will be used to compare the 2 treatment arms.

  2. PFS according to RECIST 1.1 criteria [ Time Frame: Time from randomization to the first of either disease progression or death from any cause, assessed up to 3 years ]
    PFS will be estimated using the Kaplan-Meier method, where the stratified log- rank test will be used to compare the 2 treatment groups.

  3. Incidence of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 3 years ]
    The frequency and percentage of grade 3+ adverse events will be compared between the 2 treatment arms. Comparisons between arms will be made by using either the Chi-square or Fisher's exact test.


Other Outcome Measures:
  1. Changes in the frequency of marker inhibition [ Time Frame: Baseline to up to 3 years ]
    Semi-quantitative data will be used to compare the data between the treatment arms using boxplots and descriptive statistics.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 phase 2 portion of the study 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) and at cycle 1 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 × 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
  • 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 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
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • 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
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to M6620 (VX-970), carboplatin, gemcitabine or to these specific compounds
  • VX-970 is primarily metabolized by cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); therefore, concomitant administration with strong inhibitors or inducers of CYP3A4 should be avoided
  • 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, 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02627443


Locations
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United States, Arizona
Mayo Clinic Hospital
Phoenix, Arizona, United States, 85054
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Florida
University of Florida Health Science Center - Gainesville
Gainesville, Florida, United States, 32610
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Kentucky
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States, 40536
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Pennsylvania
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States, 19107
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States, 15232
United States, Virginia
University of Virginia Cancer Center
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Andrea E Wahner Hendrickson Mayo Clinic Cancer Center LAO

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02627443     History of Changes
Other Study ID Numbers: NCI-2015-02064
NCI-2015-02064 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1563
9948 ( Other Identifier: Mayo Clinic Cancer Center LAO )
9948 ( Other Identifier: CTEP )
N01CM00099 ( U.S. NIH Grant/Contract )
P30CA015083 ( U.S. NIH Grant/Contract )
UM1CA186686 ( U.S. NIH Grant/Contract )
First Posted: December 11, 2015    Key Record Dates
Last Update Posted: May 14, 2019
Last Verified: May 2019

Additional relevant MeSH terms:
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Carcinoma
Adenocarcinoma
Fallopian Tube Neoplasms
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Cystadenocarcinoma, Serous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Endocrine Gland Neoplasms
Ovarian Diseases
Endocrine System Diseases
Gonadal Disorders
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Gemcitabine
Carboplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors