Male Breast CancerPhase 1NCT02046421
Carboplatin, Gemcitabine Hydrochloride, and Mifepristone in Treating Patients With Advanced Breast Cancer or Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer
A Phase 1 study testing mifepristone, carboplatin and gemcitabine hydrochloride in people with Male Breast Cancer and Recurrent Breast Cancer, run by University of Chicago at 2 sites in United States.
Trial summary
This phase I trial studies the side effects and best dose of gemcitabine hydrochloride and mifepristone when given together with carboplatin in treating patients with breast cancer that is metastatic or cannot be removed by surgery or recurrent or persistent ovarian epithelial, fallopian tube, or primary peritoneal… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Male Breast Cancer, Recurrent Breast Cancer, Recurrent Fallopian Tube Cancer
- What is being tested?
- mifepristone, carboplatin and gemcitabine hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2013to May 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients are eligible if they have the following: metastatic or unresectable breast cancer, recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer
- Ovarian cancer patients with both platinum-sensitive and platinum-resistant disease are eligible. Ovarian cancer patients with platinum refractory disease (failure to achieve a complete response to first line platinum therapy) are ineligible.
- Men with metastatic or unresectable breast cancer are eligible
- Patients must have measurable or evaluable disease (subjects with elevation of tumor marker with no evidence of disease on imaging or exam are not eligible)
- Patients with breast cancer may have received neoadjuvant or adjuvant chemotherapy and up to two prior chemotherapy regimens for metastatic or locally recurrent disease; subjects with ovarian cancer may have had two regimens for advanced or persistent disease
- Patients with both ER positive and ER negative breast cancer are eligible for this study. Patients with HER2 positive disease will be excluded from participation in this study.
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- Metastatic breast cancer patients who are hormone receptor positive at baseline must be hormone refractory or have indications for emergent treatment with chemotherapy (e.g., visceral crisis).
- Patients with known brain metastases will be eligible as long as they have completed radiation to the brain and have been off of corticosteroid therapy for at least 2 weeks prior to study treatment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky > 60%)
- Absolute neutrophil count >= 1,500/mL
- Platelets >= 100,000/mL
- Total bilirubin =< institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) 5 =< X institutional ULN
- Creatinine =< institutional ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Morning cortisol >= institutional normal
- If a woman is of childbearing potential, a negative serum or urine pregnancy test is required; women of child-bearing potential and men who are sexually active must agree to use birth control such as barrier method of birth control, abstinence, or else be surgically sterile (tubal ligation, hysterectomy or partner with confirmed vasectomy) prior to study entry and for the duration of study participation; hormonal contraception is not permitted on trial; alternatively the patient must be post-menopausal defined as greater than 12 months without a menstrual cycle; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; nursing patients must discontinue breast feeding prior to the initiation of therapy
- Ability to understand and willingness to sign an informed consent document
- Bisphosphonate (e.g. zoledronic acid) and receptor activator of nuclear transcription factor kappa-B (NF-kappaB) ligand (RANKL) inhibitor (e.g. denosumab) use for bone metastasis is permitted
Who cannot join
- Patients who have not recovered from toxicities of prior therapy to the point that they would be appropriate for re-dosing will be ineligible for study treatment. All patients must have a two week washout period from prior chemotherapy.
- Patients must be at least two weeks from prior radiation therapy (RT)
- Patients must have a one week washout period from prior hormonal therapy (e.g. testosterone, estrogen, progestin, gonadotropin-releasing hormone antagonist)
- Patients may not be receiving any other investigational agents
- Mifepristone inhibits cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) and induces CYP3A4; addition of mifepristone to a pre-existing drug regimen may cause a mild and temporary increase in plasma drug concentration of drugs with significant CYP3A4 metabolism; medications that are strong inducers of CYP3A4 such as carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, St. John's Wort may decrease plasma mifepristone levels; strong CYP3A4 inhibitor medications are expected to cause the largest increases in plasma mifepristone concentrations; mifepristone may increase the plasma drug concentration of concomitant medications with metabolism mediated by cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9)/cytochrome P450, family 2, subfamily C, polypeptide 8 (2C8)
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, poorly controlled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
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- Pregnant women are excluded from this study; breastfeeding should be discontinued if patient wishes to participate in study
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- History of long-term use of corticosteroids or concurrent short-term use of corticosteroids is not allowed; short-term corticosteroid use must be discontinued at least 2 weeks prior to study treatment
- Prior mifepristone use for anticancer therapy is not allowed
- Patients with advanced breast cancer who have received platinum therapy (e.g. carboplatin or cisplatin) and/or gemcitabine therapy for metastatic disease are excluded (platinum-based therapy and/or gemcitabine in the adjuvant or neoadjuvant setting is allowed)
- Ovarian cancer patients who have received prior gemcitabine therapy are ineligible; (prior carboplatin therapy is allowed)
- Patients with known grade 2 or greater allergic reactions attributed to compounds of similar chemical or biologic composition to mifepristone, carboplatin, or gemcitabine are ineligible for study enrollment
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637-1470
NorthShore University HealthSystem
Evanston, Illinois, 60201
About this study
Official title: Carboplatin, Gemcitabine, and Mifepristone for Advanced Breast Cancer and Recurrent or Persistent Epithelial Ovarian Cancer
This phase I trial studies the side effects and best dose of gemcitabine hydrochloride and mifepristone when given together with carboplatin in treating patients with breast cancer that is metastatic or cannot be removed by surgery or recurrent or persistent ovarian epithelial, fallopian tube, or primary peritoneal cancer. 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 or by stopping them from dividing. Steroid hormones can cause the growth of cancer cells. Hormone therapy using mifepristone may fight breast and ovarian cancer by lowering the amount of steroid hormone the body makes. Giving carboplatin and gemcitabine hydrochloride together with mifepristone may be an effective treatment for breast, ovarian epithelial, fallopian tube, or primary peritoneal cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of mifepristone when given in combination with carboplatin and gemcitabine (gemcitabine hydrochloride).
SECONDARY OBJECTIVES:
- To determine the safety and tolerability of mifepristone in combination with carboplatin and gemcitabine.
II. To describe the toxicities seen with carboplatin, gemcitabine, and mifepristone combination therapy.
TERTIARY OBJECTIVES:
- To correlate expression of biomarkers (e.g. glucocorticoid receptor [GR], androgen receptor [AR], estrogen receptor [ER], and progesterone receptor [PR]) with treatment outcomes.
II. To correlate serum and intratumoral mifepristone concentrations after two doses of mifepristone (in patients with easily accessible tumor who consent to an optional research biopsy).
OUTLINE: This is a dose-escalation study of mifepristone.
Patients receive mifepristone orally (PO) once daily (QD) on days 0, 1, 7, and 8, and carboplatin intravenously (IV) over 30 minutes and gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 18 months.
- Conditions
- Male Breast Cancer, Recurrent Breast Cancer, Recurrent Fallopian Tube Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Primary Peritoneal Cavity Cancer, Stage IIIB Breast Cancer
- Being tested
- mifepristone, carboplatin, gemcitabine hydrochloride, laboratory biomarker analysis, pharmacological study
- Medical subject headings
- Breast Neoplasms, Male, Breast Neoplasms, Fallopian Tube Neoplasms, Carcinoma, Ovarian Epithelial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mifepristoneDrug
Also called Mifegyne, Mifeprex, RU-38486
Given PO
carboplatinDrug
Also called Carboplat, CBDCA, JM-8, Paraplat
Given IV
Also called dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
Given IV
laboratory biomarker analysisOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (mifepristone, carboplatin, gemcitabine) | Experimental | Patients receive mifepristone PO QD on days 0, 1, 7, and 8, and carboplatin IV over 30 minutes and gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: mifepristone; Drug: carboplatin; Drug: gemcitabine hydrochloride; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD/RP2D, defined as < 1/6 patients at highest dose level below max administered dose or fewer than 33% of patients experiencing dose limiting toxicity (DLT), graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0
Summarized by type and grade overall and for each dose level. Confidence intervals for the proportion of patients experiencing a DLT will be constructed.
Measured: 21 days
Secondary outcomes (3)
Response to treatment according to Response Evaluation Criteria in Solid Tumors 1.1
Measured: Up to 12 weeks
Progression free survival (PFS)
Estimated using the method of Kaplan-Meier, and compared between groups using the logrank test. In addition, the association between GR expression status and PFS or overall survival (OS) will be examined using Cox proportional hazards regression with GR status and dose level as covariates.
Measured: Up to 18 months
OS
Estimated using the method of Kaplan-Meier, and compared between groups using the logrank test. In addition, the association between GR expression status and PFS or OS will be examined using Cox proportional hazards regression with GR status and dose level as covariates.
Measured: Up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2014 (estimated)
- Study startNov 2013
- Primary completionMay 2018
- Study completionMay 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Male Breast CancerStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Rita Nanda, Principal investigator, University of Chicago Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02046421
- Sponsor's protocol ID
- IRB13-1000
- Other IDs
- NCI-2014-00107, IRB13-1000, P30CA014599
- Status last verified
- Sep 2018
- First submitted
- 23 Jan 2014
- Last updated
- 11 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Carboplatin, Gemcitabine, and Mifepristone for Advanced Breast Cancer and Recurrent or Persistent Epithelial Ovarian Cancer
- ClinicalTrials.gov ID
- NCT02046421
- Acronym / sponsor ID
- IRB13-1000
- Conditions
- Male Breast Cancer, Recurrent Breast Cancer, Recurrent Fallopian Tube Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Primary Peritoneal Cavity Cancer, Stage IIIB Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Nov 2013 (actual)
- Primary completion
- May 2018 (actual)
- Study completion
- May 2018 (actual)
- First posted
- 27 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and best dose of gemcitabine hydrochloride and mifepristone when given together with carboplatin in treating patients with breast cancer that is metastatic or cannot be removed by surgery or recurrent or persistent ovarian epithelial, fallopian tube, or primary peritoneal cancer. 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 or by stopping them from dividing. Steroid hormones can cause the growth of cancer cells. Hormone therapy using mifepristone may fight breast and ovarian cancer by lowering the amount of steroid hormone the body makes. Giving carboplatin and gemcitabine hydrochloride together with mifepristone may be an effective treatment for breast, ovarian epithelial, fallopian tube, or primary peritoneal cancer.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of mifepristone when given in combination with carboplatin and gemcitabine (gemcitabine hydrochloride).
SECONDARY OBJECTIVES:
- To determine the safety and tolerability of mifepristone in combination with carboplatin and gemcitabine.
II. To describe the toxicities seen with carboplatin, gemcitabine, and mifepristone combination therapy.
TERTIARY OBJECTIVES:
- To correlate expression of biomarkers (e.g. glucocorticoid receptor [GR], androgen receptor [AR], estrogen receptor [ER], and progesterone receptor [PR]) with treatment outcomes.
II. To correlate serum and intratumoral mifepristone concentrations after two doses of mifepristone (in patients with easily accessible tumor who consent to an optional research biopsy).
OUTLINE: This is a dose-escalation study of mifepristone.
Patients receive mifepristone orally (PO) once daily (QD) on days 0, 1, 7, and 8, and carboplatin intravenously (IV) over 30 minutes and gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 18 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (mifepristone, carboplatin, gemcitabine) | Experimental | Drug: mifepristone, Drug: carboplatin, Drug: gemcitabine hydrochloride, Other: laboratory biomarker analysis, Other: pharmacological studyPatients receive mifepristone PO QD on days 0, 1, 7, and 8, and carboplatin IV over 30 minutes and gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients are eligible if they have the following: metastatic or unresectable breast cancer, recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer
- Ovarian cancer patients with both platinum-sensitive and platinum-resistant disease are eligible. Ovarian cancer patients with platinum refractory disease (failure to achieve a complete response to first line platinum therapy) are ineligible.
- Men with metastatic or unresectable breast cancer are eligible
- Patients must have measurable or evaluable disease (subjects with elevation of tumor marker with no evidence of disease on imaging or exam are not eligible)
- Patients with breast cancer may have received neoadjuvant or adjuvant chemotherapy and up to two prior chemotherapy regimens for metastatic or locally recurrent disease; subjects with ovarian cancer may have had two regimens for advanced or persistent disease
Key exclusion criteria (13 listed)
- Patients who have not recovered from toxicities of prior therapy to the point that they would be appropriate for re-dosing will be ineligible for study treatment. All patients must have a two week washout period from prior chemotherapy.
- Patients must be at least two weeks from prior radiation therapy (RT)
- Patients must have a one week washout period from prior hormonal therapy (e.g. testosterone, estrogen, progestin, gonadotropin-releasing hormone antagonist)
- Patients may not be receiving any other investigational agents
- Mifepristone inhibits cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) and induces CYP3A4; addition of mifepristone to a pre-existing drug regimen may cause a mild and temporary increase in plasma drug concentration of drugs with significant CYP3A4 metabolism; medications that are strong inducers of CYP3A4 such as carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, St. John's Wort may decrease plasma mifepristone levels; strong CYP3A4 inhibitor medications are expected to cause the largest increases in plasma mifepristone concentrations; mifepristone may increase the plasma drug concentration of concomitant medications with metabolism mediated by cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9)/cytochrome P450, family 2, subfamily C, polypeptide 8 (2C8)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mifepristoneAlso: Mifegyne, Mifeprex, RU-38486Given PO | Drug | Treatment (mifepristone, carboplatin, gemcitabine) |
| carboplatinAlso: Carboplat, CBDCA, JM-8, ParaplatGiven IV | Drug | Treatment (mifepristone, carboplatin, gemcitabine) |
| gemcitabine hydrochlorideAlso: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, GemzarGiven IV | Drug | Treatment (mifepristone, carboplatin, gemcitabine) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (mifepristone, carboplatin, gemcitabine) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (mifepristone, carboplatin, gemcitabine) |
Primary outcome
MTD/RP2D, defined as < 1/6 patients at highest dose level below max administered dose or fewer than 33% of patients experiencing dose limiting toxicity (DLT), graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0
Time frame: 21 days
Summarized by type and grade overall and for each dose level. Confidence intervals for the proportion of patients experiencing a DLT will be constructed.
3 secondary outcomes
Response to treatment according to Response Evaluation Criteria in Solid Tumors 1.1
Time frame: Up to 12 weeks
Progression free survival (PFS)
Time frame: Up to 18 months
OS
Time frame: Up to 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rita Nanda principal investigator
University of Chicago Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing mifepristone, carboplatin and gemcitabine hydrochloride in people with Male Breast Cancer and Recurrent Breast Cancer, run by University of Chicago at 2 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 18 inclusion and 13 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: finished, as of the sponsor's last update on 11 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
MTD/RP2D, defined as < 1/6 patients at highest dose level below max administered dose or fewer than 33% of patients experiencing dose limiting toxicity (DLT), graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0 (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Sep 2018.