AzTrials
AzTrials

Triple Negative Breast CancerPhase 2NCT02768701

Study Of Single-dose Cyclophosphamide +Pembrolizumab In Patients With Metastatic Triple Negative Breast Cancer

A Phase 2 study testing Pembrolizumab and Cyclophosphamide in people with Triple Negative Breast Cancer, run by UNC Lineberger Comprehensive Cancer Center at 5 sites in United States.

Completed

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

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate pembrolizumab therapy in patients with triple-negative breast cancer (TNBC) who have received at least one prior line of therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Triple Negative Breast Cancer
What is being tested?
Pembrolizumab and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
5 sitesUnited States
Study dates
18 Oct 2016to 1 May 2023
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • Age ≥ 18 years at the time of consent.
  • Have measurable disease based on RECIST 1.1 (see section 6.7 for details).
  • ECOG Performance Status ≤ 1 as defined in the protocol ECOG Performance Status.
  • Subject must have histologically confirmed stage IV TNBC (ER-, PR-, HER2-negative) and have received at least 1 prior line of systemic therapy.
  • ER- and PR-negative: defined as < 1% staining by immunohistochemistry (IHC)
Show all 19Show fewer
  • HER2-negative disease, defined as IHC 0-1+ or fluorescence in situ hybridization (FISH) ratio < 2.0
  • Patients with stable brain metastases will be allowed provided the following criteria are met:
  • Brain radiation was already provided at least 4 weeks prior to initiating study treatment
  • The subject has no new or progressive neurologic symptoms AND neurological symptom stability for the last 4 weeks prior to the study
  • The subject has been off of corticosteroids for at least 7 days prior to trial treatment
  • The subject does not have carcinomatous meningitis
  • Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 72 h of initiating study treatment.
  • Females of childbearing potential must have a negative serum pregnancy test within 72 hrs prior to treatment. NOTE: Females are considered of child bearing potential unless they are surgically sterile, have a congenital acquired condition that prevents childbearing (have undergone a hysterectomy, bilateral tubal ligation/occlusion, bilateral salpingectomy or bilateral oophorectomy at least 6 weeks prior to screening) or they are naturally postmenopausal for at least 12 consecutive months without an alternative medical cause. In women < 45 years of age a high follicle stimulating hormone level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
  • Female patients of childbearing potential should be willing to use appropriate birth control as outlined in Section 5.2.8, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.
  • Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section 5.2.8, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • Consent for the use of any residual material from biopsy (archival tissue) and serial blood draws will be required for enrollment; fresh biopsy (pre and post dose) of tumor tissue will be optional. NOTE: Patients without adequate tissue for bio correlates will not be excluded or required to have a repeat biopsy.
  • As determined by the enrolling physician or protocol designee, the subject should be able to understand and comply with study procedures for the entire length of the study.
  • Has a LVEF within the normal institutional range (or ≥ 50%) based on ECHO or MUGA.

Who cannot join

  • Active infection requiring systemic therapy
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Has a known history of active Bacillus Tuberculosis (TB)
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to receipt of study medication or who has not recovered (i.e., ≤ Grade 1 or at baseline; excludes alopecia and Grade 2 neuropathy) from adverse events due to a previously administered agent.
Show all 24Show fewer
  • If subject had major surgery, they must have recovered adequately from the toxicity and complications from the intervention prior to starting therapy
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has had monoclonal antibody therapy within 4 weeks prior to study Day 1 or who has not recovered (ie, ≤ Grade 1 at baseline; excludes alopecia and Grade 2 neuropathy) from adverse events due to agent(s) administered more than 4 weeks earlier.
  • Treatment with any investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of study medication.
  • Used an investigational device within 4 weeks of the first dose of treatment.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has known history of, or any evidence of active, non-infectious pneumonitis requiring treatment with steroids; has history of, or any evidence of, active interstitial lung disease.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has participated in a previous trial and received pembrolizumab therapy
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment.
  • Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed
  • Cyclophosphamide is a substrate for cytochromes 2B6, 2C9, 3A4 and 2C19. Patients must not have received any drug that is a moderate or strong inhibitor of 2B6, 2C9, 3A4, and 2C19 within 1 week prior to receiving cyclophosphamide dosing through 72 hours after cyclophosphamide dosing. Patients must not have received any drug that is a moderate or strong inducer of 3A4 within 2 weeks prior to cyclophosphamide dosing.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites
  • Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Cone Health Cancer Center

    Greensboro, North Carolina, 27403

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • Rex Cancer Center

    Raleigh, North Carolina, 27607

  • George Washington University-Medical Faculty Associates

    Washington D.C., District of Columbia, 20037

Other trials in United States

About this study

Official title: Phase II Study Of Single-dose Cyclophosphamide +Pembrolizumab In Patients With Metastatic Triple Negative Breast Cancer

The purpose of this study is to evaluate pembrolizumab therapy in patients with triple-negative breast cancer (TNBC) who have received at least one prior line of therapy.

Read the detailed description

This phase II, single-arm, multicenter study will evaluate efficacy and toxicity of administration of pembrolizumab following cyclophosphamide therapy, in advanced stage triple-negative breast cancer.

Duration of Therapy

Treatment may continue until one of the following occurs:

  • Disease progression
  • Inter-current illness that prevents further administration of treatment
  • Unacceptable adverse event(s)
  • Pregnancy
  • Patient decides to withdraw from study treatment,
  • General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator
  • Completed 24 months of uninterrupted treatment with pembrolizumab or 35 administrations of study medication, whichever is later

Duration of Follow Up

  • Subjects will be followed for up to 3 years after removal from study treatment or until death, whichever occurs first.
  • Patients removed from study for unacceptable adverse events (AEs) will be followed until resolution or stabilization of the event(s).
Keywords
Pembrolizumab, cyclophosphamide
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

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

  • PembrolizumabDrug

    Also called Keytruda

    Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion.

  • CyclophosphamideDrug

    Also called Cytoxan, Neosar

    A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.

Study groups in NCT02768701
Study groupRoleWhat they receive
Experimental: Single ArmExperimentalSubjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks.
Receives: Drug: Pembrolizumab; Drug: Cyclophosphamide

What is being measured

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

  1. The Progression Free Survival (PFS)

    PFS is defined as the time from day1 of the study treatment until disease progression or death. Disease progression is defined as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST)1.1 based on computerized tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) images or assessment of the physician.

    RECIST v.1.1: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Measured: Up to 5 years

  2. Quantification of the Change in Regulatory T Cells (Tregs) During the Study Treatment.

    Regulatory T cells (Tregs) are counted before the treatment start and during the treatment. Methods: Blood Sample collection.

    Measured: Up to 2 years

Secondary outcomes (5)
  1. Overall Response Rate (ORR)

    ORR is defined as the percentage of patients with [compete response (CR) + partial response (PR)] per RECIST1.1 based on computerized tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) images.

    RECIST v.1.1: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions;

    Measured: Up to 2 years

  2. Duration of Response (DOR)

    DOR is defined as the time from documentation of tumor response by RECIST1.1 [(CR) + (PR)] to disease progression by RECIST 1.1. It will be measured from when the time measurement criteria are first met for complete response or partial response (whichever status is recorded first) until the first date of progressive disease or death. Patients who neither progress nor die will be censored on the date of their last tumor assessment.

    Measured: Up to 3 years

  3. Disease Control Rate (DCR)

    DCR is defined as the percentage of participants, who achieve [compete response (CR) + partial response (PR) and stable disease (SD) per RECIST1.1. If best response is SD, then it must last more than 6 months to be included in calculation of DCR, to be considered to have received clinical benefit from the treatment regimen.

    RECIST v.1.1: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Measured: Up to 2 years

  4. Overall Survival (OS)

    OS is defined as the time from D1 of study treatment to death from any cause.

    Measured: Up to 3 years

  5. Treatment Associated Toxicity

    Treatment Associated Toxicity is defined as the number of participants with Grade 3-4 adverse events associated with study treatment.

    Adverse Events were classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.4 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.

    Measured: 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 posted11 May 2016 (estimated)
  2. Study start18 Oct 2016
  3. Primary completion1 May 2022
  4. Study completion1 May 2023

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02768701
Sponsor's protocol ID
LCCC 1525
Status last verified
May 2023
First submitted
5 May 2016
Last updated
22 May 2023
Data monitoring committee
Yes
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Cyclophosphamide in people with Triple Negative Breast Cancer, run by UNC Lineberger Comprehensive Cancer Center at 5 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 19 inclusion and 24 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 22 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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 3 Aug 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?

The Progression Free Survival (PFS) (time frame: Up to 5 years). The study lists 2 primary outcomes in all. 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 22 May 2023.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in