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Estrogen Receptor NegativePhase 1NCT01624441

Dinaciclib and Epirubicin Hydrochloride in Treating Patients With Metastatic Triple-Negative Breast Cancer

A Phase 1 study testing Dinaciclib, Epirubicin Hydrochloride and Laboratory Biomarker Analysis in people with Estrogen Receptor Negative and HER2/Neu Negative, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I clinical trial studies the side effects and the best dose of dinaciclib when given together with epirubicin hydrochloride (epirubicin) in patients with metastatic (cancer that has spread to other parts of the body) triple-negative breast cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Dinaciclib, Epirubicin Hydrochloride and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
21 Aug 2012to 10 Sep 2013
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 must have histologically confirmed estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2) negative carcinoma of the breast that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; for purposes of this study, triple negative disease will be tumors that have ER/PR < 10% and HER2 =< 1+ by immunohistochemistry (IHC) or HER2 fluorescent in situ hybridization (FISH) non-amplified (ratio < 2)
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Patients must have no more than two prior chemotherapy regimens for metastatic breast cancer; in patients who develop disease recurrence within 6 months of adjuvant or neoadjuvant chemotherapy, the adjuvant or neoadjuvant therapy will be considered one prior regimen for metastatic disease
  • Life expectancy of greater than 3 months
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
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  • Total bilirubin within normal limits unless clinical diagnosis of Gilbert's syndrome
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Patients must be disease free of prior malignancy for >= 5 years with the exception of curatively treated squamous cell carcinomas of the skin or carcinoma in situ of the cervix or breast
  • Must have at least one site of objective measurable or evaluable disease; baseline measurements and evaluations must be obtained within 4 weeks of start of therapy
  • Patients must have no history of prior therapy with dinaciclib
  • Concurrent use of hormonal therapy is not permitted; concurrent radiation therapy is not permitted; bisphosphonates are allowed, provided that they were started no less than two weeks prior to initiating protocol therapy
  • Patients must have completed and recovered from the effects of prior chemotherapy (< grade 2 toxicity) excluding alopecia
  • Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; 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; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of dinaciclib administration
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events
  • Patients who are receiving any other investigational agents
  • Patients with untreated brain metastases should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition as epirubicin or dinaciclib
  • Patients receiving any medications or substances that are inhibitors or inducers of cytochrome P450 family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) are ineligible
  • 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
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  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with dinaciclib
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Patients who have had prior organ allograft or require immunosuppressive therapy
  • Patients who have received a cumulative dose of doxorubicin of greater than 360 mg/m^2 or epirubicin of greater than 600 mg/m^2; patients who have received > 240 mg/m^2 of doxorubicin or > 400 mg/m^2 of epirubicin should be advised to undergo evaluation of left ventricular ejection fraction (LVEF) with echocardiogram or multi gated acquisition scan (MUGA) prior to initiating therapy
  • Patients with a history of New York Heart Association class 3 or 4 heart failure, or history of myocardial infarction, unstable angina or cerebral vascular accident (CVA) within 6 months of protocol registration
  • LVEF < 50% by MUGA or echocardiogram (ECHO)
  • Patients who have history of PR prolongation or atrioventricular (AV) block

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase 1 Study With Dose Expansion of Dinaciclib (SCH 727965) in Combination With Epirubicin in Patients With Metastatic Triple Negative Breast Cancer

This phase I clinical trial studies the side effects and the best dose of dinaciclib when given together with epirubicin hydrochloride (epirubicin) in patients with metastatic (cancer that has spread to other parts of the body) triple-negative breast cancer. Dinaciclib is designed to stop cancer cells from dividing into new cancer cells. Epirubicin is designed to block the way cancer cells grow and divide and may slow or stop cancer cells from spreading throughout the body. Researchers want to find out what is the highest tolerable dose of the experimental drug dinaciclib that can be given in combination with epirubicin in patients with metastatic triple negative breast cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of dinaciclib given in combination with epirubicin in patients with metastatic triple negative breast cancer.

SECONDARY OBJECTIVES:

  1. To determine the predictive value of myeloid cell leukemia sequence 1 protein (MCL-1), low molecular weight cyclin E (LMW-E), and tumor grade as predictors of biologic response (i.e. induction of apoptosis) in tumors treated with therapy.

II. To evaluate the efficacy of combination therapy. III. To determine the effects of therapy on proliferation as measured by proliferation-related Ki-67 antigen (Ki67) and apoptosis as measured by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay (TUNEL).

OUTLINE: This is a dose-escalation study of dinaciclib.

Patients receive dinaciclib intravenously (IV) over 2 hours on day 1 and epirubicin hydrochloride IV over 30 minutes on day 2. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Being tested
Dinaciclib, Epirubicin Hydrochloride, Laboratory Biomarker Analysis
Medical subject headings
Breast Neoplasms, Male, Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

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

  • DinaciclibDrug

    Also called CDK Inhibitor SCH 727965, MK-7965, SCH 727965

    Given IV

  • Epirubicin HydrochlorideDrug

    Also called Ellence, IMI-28, Pharmorubicin PFS

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT01624441
Study groupRoleWhat they receive
Treatment (dinaciclib and epirubicin hydrochloride)ExperimentalPatients receive dinaciclib IV over 2 hours on day 1 and epirubicin hydrochloride IV over 30 minutes on day 2. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Dinaciclib; Drug: Epirubicin Hydrochloride; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. MTD of dinaciclib given in combination with epirubicin hydrochloride, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4

    The number (%) of DLTs will tabulate by dose level of dinaciclib.

    Measured: 21 days

Secondary outcomes (3)

  1. Predictive value of MCL-1, LMW-E, and tumor grade as predictors of biologic response (i.e. induction of apoptosis) in tumors treated with therapy

    A logistic regression model will be used to assess whether the expression level of LMW-E can predict clinical benefit, adjusted for dose level and other potential prognostic factors: visceral organ involvement (present vs. absent), number of prior therapies for metastatic breast cancer (0-2 or > 2), age (< 60 vs. > 60) and ECOG performance status (0-1 vs. 2).

    Measured: Up to 30 days after completion of study treatment

  2. Clinical benefit rate (complete response [CR] + partial response [PR] + stable disease [SD]), assessed using Response Evaluation Criteria in Solid Tumors (RECIST)

    The overall clinical benefit rate for patients treated at the MTD will be estimated with a 90% credible interval.

    Measured: At 6 months

  3. Changes in proliferation as measured by Ki67 and apoptosis as measured by TUNEL

    For the patients with pre- and post- treatment biopsies, summary statistics used to describe change in apoptotic index pre- to post-treatment, and boxplots to illustrate distribution pre- and post-treatment, as well as distribution of change. Mean change estimated with 95% confidence interval. MCL-1, LMW-E, and Ki67 similarly analyzed. Analyses also performed stratified by tumor grade. Correlation between changes in MCL-1 and LMW-E pre- to post-treatment estimated with 95% confidence interval. Number of tumors in 4 categories (negative, low, medium, high) tabulated by % of TUNEL+ tumor cells.

    Measured: From baseline to 2 weeks

Timeline

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

  1. First posted20 Jun 2012 (estimated)
  2. Study start21 Aug 2012
  3. Primary completion10 Sep 2013
  4. Study completion10 Sep 2013

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01624441
Sponsor's protocol ID
NCI-2012-00950
Other IDs
NCI-2012-00950, 2012-0229, 9138, P30CA016672, R01CA152228, U01CA062461
Status last verified
Mar 2018
First submitted
18 Jun 2012
Last updated
30 Mar 2018
Results posted
No

Publications

  • Mitri Z, Karakas C, Wei C, Briones B, Simmons H, Ibrahim N, Alvarez R, Murray JL, Keyomarsi K, Moulder S. A phase 1 study with dose expansion of the CDK inhibitor dinaciclib (SCH 727965) in combination with epirubicin in patients with metastatic triple negative breast cancer. Invest New Drugs. 2015 Aug;33(4):890-4. doi: 10.1007/s10637-015-0244-4. Epub 2015 May 7.

    PubMed 25947565

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dinaciclib, Epirubicin Hydrochloride and Laboratory Biomarker Analysis in people with Estrogen Receptor Negative and HER2/Neu Negative, run by National Cancer Institute (NCI) at 1 site 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 16 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 30 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 of dinaciclib given in combination with epirubicin hydrochloride, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4 (time frame: 21 days). 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 NCT01624441, which also lists 1 linked publication.

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 30 Mar 2018.

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