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Breast - FemalePhase 2PePPyNCT03018080

Pilot Study of Paclitaxel Plus Pembrolizumab in Metastatic HER2-Negative Breast Cancer

A Phase 2 study testing Pembrolizumab and Paclitaxel in people with Breast - Female and Male Breast Cancer, run by Wake Forest University Health Sciences 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

The primary objective of this study is to assess the safety and feasibility of the following two regimens: Cohort A) phased regimen of pembrolizumab in which paclitaxel is followed by paclitaxel plus pembrolizumab and Cohort B) concurrent regimen of paclitaxel plus pembrolizumab. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast - Female, Male Breast Cancer
What is being tested?
Pembrolizumab and Paclitaxel
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
12 Jun 2017to 5 Aug 2022
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

  • Subjects must meet all of the following criteria:
  • Histologically or cytological confirmed diagnosis of HER2-negative metastatic breast cancer or locally advanced disease not amenable to resection.
  • Available ER and PR status from tumor sample with either hormone receptor positive or negative tumor(s).
  • For subjects with hormone receptor-positive, HER2-negative metastatic breast cancer, they are eligible if they have already received or been intolerant to at least two lines of endocrine therapies (including the adjuvant and/or metastatic setting), or are appropriate candidates for chemotherapy (i.e. large burden of visceral disease).
  • Measurable disease by RECIST 1.1, or evaluable bone disease, i.e., bone lesions that are lytic or mixed (i.e. lytic + sclerotic) in the absence of measurable lesion. Refer to section 11 for the evaluation of measurable disease.
  • Male or female age ≥18 years.
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  • ECOG performance status 0, 1 or 2.
  • Must have normal organ and marrow function as defined below:
  • Hematologic - Absolute neutrophil count ≥1,500/mcL
  • Platelets ≥75,000/mcL
  • Hemoglobin ≥ 9 g/dL
  • Renal
  • Creatinine ≤ 1.5X ULN or
  • Measured or calculated creatinine clearance (CrCl) ≥ 30 mL/min for subject with creatinine levels > 1.5X ULN [CrCl should be calculated per institutional standard; GFR can also be used in place of creatinine or CrCl]
  • Hepatic
  • Total bilirubin ≤1.5X ULN or for subjects with total bilirubin levels >1.5X ULN, direct bilirubin ≤ULN
  • AST(SGOT)/ALT(SGPT) ≤2.5X ULN
  • Coagulation
  • PT and PTT ≤ 1.5X ULN; subjects receiving anticoagulant therapy are eligible if PT or PTT is within therapeutic range of intended use of anticoagulants per investigator discretion.
  • INR ≤ 1.5; Patients receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation per investigator discretion.
  • Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to receiving C1D1.
  • Female subjects of childbearing potential must be willing to use an adequate method of birth control as outlined in Section 8.1.10, be surgically sterile, or abstain from heterosexual activity for the course of the study and 120 days after the last dose of study therapy. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Male subjects of reproductive potential should agree to use an adequate method of contraception starting with the first dose of study therapy and 120 days after the last dose of study therapy. Abstinence is acceptable if this is the established and preferred contraception for the subject.
  • Has completed the screening requirement of a core or punch biopsy of a tumor lesion per Section 5 (bone tissue not acceptable). Biopsy of the breast tumor or other regional areas is acceptable (i.e. lymph nodes, skin lesions).
  • Subjects who are unable to meet the screening requirement of a tumor biopsy due to inaccessible tumor, subject safety concern, or bone-only disease may submit an archived tumor specimen from primary tumor or metastatic biopsy collected within 12 months from consent.
  • Subjects who decline tumor biopsy may submit archived tumor specimen as specified above (within 12 months from consent) only after Sponsor-Investigator approval.
  • Ability to understand and the willingness to sign the written informed consent document.

Who cannot join

  • Subjects must not meet any of the following criteria:
  • Prior chemotherapy within 3 weeks, prior targeted small molecule therapy or radiation therapy within 2 weeks, or prior anti-cancer monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks prior to Cycle 1 Day 1.
  • Not recovered (i.e., ≤ Grade 1) from adverse events due to agents previously administered.
  • o Note: Subjects with ≤ Grade 2 neuropathy or alopecia of any grade are an exception and may qualify for the study.
  • More than three prior lines of chemotherapy for HER2-negative metastatic disease or for locally advanced disease that is not amenable to resection.
  • o Note: Non-Chemotherapy regimens do not count as prior lines (ex: hormonals, biologics)
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  • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137) or has participated in Merck MK-3475 trial(s) and received MK-3475 as part of protocol therapy.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Cycle 1 Day 1
  • Has had major surgery within 3 weeks prior to Cycle 1 Day 1.
  • Has received any other investigational agents within 4 weeks of Cycle 1 Day 1 of study therapy.
  • Known active uncontrolled or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
  • o Note: Subjects with treated CNS metastases are eligible if they are asymptomatic, have no requirement for steroids, no requirement for anticonvulsants, and stable CNS radiographic study showing no significant vasogenic edema ≥ 4 weeks since completion of radiation and ≥ 2 weeks since discontinuation of steroids.
  • History of known allergic reaction to paclitaxel
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might 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.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment. Pregnant women are excluded from this study because paclitaxel is an agent with 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 paclitaxel, breastfeeding should be discontinued if the mother is treated with paclitaxel. These potential risks also apply to pembrolizumab being used in this study.
  • Has a known history of Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency disorder (AIDS). HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with paclitaxel and pembrolizumab. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
  • Has known active infection with hepatitis B or hepatitis C.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
  • o Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has a known additional malignancy that progressed or required active treatment within the last 5 years.
  • o Note: Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Has received a live vaccine within 30 days of Cycle 1 Day 1 of study therapy. o Note: 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

Other trials in United States

About this study

Official title: LCI-BRE-H2N-PEPP-001: A Pilot Study of Paclitaxel Plus Pembrolizumab in Patients With Metastatic HER2-Negative Breast Cancer (The PePPy Trial)

The primary objective of this study is to assess the safety and feasibility of the following two regimens: Cohort A) phased regimen of pembrolizumab in which paclitaxel is followed by paclitaxel plus pembrolizumab and Cohort B) concurrent regimen of paclitaxel plus pembrolizumab. The primary safety objective is to evaluate the overall grade 3 or 4 treatment-related adverse event rate for each cohort and compare them to relevant historical controls.

Read the detailed description

This is an open-label randomized pilot research study to determine if the study drug, pembrolizumab, is safe to use in combination with a chemotherapy drug called paclitaxel. This study will have the following two regimens: Cohort A) phased regimen of pembrolizumab in which paclitaxel is followed by paclitaxel plus pembrolizumab and Cohort B) concurrent regimen of paclitaxel plus pembrolizumab. A total of 40 evaluable subjects will be enrolled over an enrollment period of 18-24 months. The study is planned to enroll approximately 20 evaluable subjects in each treatment cohort.

Medical subject headings
Breast Neoplasms, Male

What participants receive

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

  • PembrolizumabDrug

    Also called Keytruda

    IV (in the vein) on day 1 of a 21 day cycle

  • PaclitaxelDrug

    Also called Taxol

    IV (in the vein) on days 1 and 8 of a 21 day cycle

Study groups in NCT03018080
Study groupRoleWhat they receive
Arm A (Phased Pembrolizumab Regimen)ExperimentalPaclitaxel will be given as an IV infusion over 60 minutes, on days 1 and 8 every 21 (+/- 3) days during Cycles 1 and 2. No pembrolizumab will be given during Cycles 1 and 2. Starting with cycle 3 and subsequent cycles, pembrolizumab will be given as an IV infusion over 30 minutes before paclitaxel on day 1 every 21 (+/- 3) days.
Receives: Drug: Pembrolizumab; Drug: Paclitaxel
Arm B (Concurrent Pembrolizumab Regimen)ExperimentalPembrolizumab will be given as an IV infusion on day 1 before paclitaxel every 21 (+/- 3) days. Paclitaxel will be given as an IV infusion over 60 minutes, on days 1 and 8 every 21 (+/- 3) days.
Receives: Drug: Pembrolizumab; Drug: Paclitaxel

What is being measured

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

  1. Number of Participants With at Least One Grade 3 or 4 Treatment-related Adverse Event

    Grade 3 or 4 study treatment-related adverse events will be determined for each subject as a binary variable indicating whether or not the subject experienced at least one grade 3 or 4 study treatment-related adverse events according to the NCI Common Terminology for Adverse Events, version 4.0. An adverse event will be considered study treatment related if it is determined that the event is at least possibly related to either paclitaxel, pembrolizumab, or both.

    Measured: From enrollment to at least 30 days following cessation of study treatment. The median time on treatment was 5.5 months.

Secondary outcomes (5)

  1. Number of Subjects With an Objective Response (Per RECIST V1.1)

    Objective response was determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of complete response (CR) or partial response (PR) as determined by RECIST 1.1 response criteria. A CR is indicated by disappearance of all target and non target lesions. A PR is indicated by >=30% decrease in sum of longest diameter of target lesions with baseline as reference.

    Measured: From enrollment to best response while on study treatment; subjects remained on treatment until disease progression or death or unacceptable toxicity (subjects were on treatment for a median of 5.5 months)

  2. Progression-free Survival (PFS) Per RECIST 1.1

    PFS is defined as the duration of time from treatment start date to first occurrence of either progressive disease (PD) or death. PD must be objectively determined per RECIST 1.1 criteria, where progression date is date of last assessment that identified PD. If subject died without documented PD, progression date will be death date. For surviving subjects who do not have PD, PFS will be censored at the date of last disease assessment. For subjects who received subsequent anti-cancer therapy prior to documented PD, PFS will be censored at the date of last disease assessment prior to commencement of subsequent therapy. Subjects who have an initial PFS event immediately following 2 or more consecutive missed assessments will be censored at date of last assessment prior to missed assessments.

    Measured: From treatment start date to date of progression/death, or censored as described; assessed for approximately 2 years.

  3. Overall Survival (OS)

    OS is defined as the duration from treatment start date to the date of death from any cause. Subjects who are alive or lost to follow up at the time of the analysis will be censored at the last known date they were alive.

    Measured: From date of treatment start to date of death, or censored as described; assessed for approximately 5 years.

  4. Number of Subjects With Disease Control (Per RECIST V1.1)

    Disease control was determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of complete response (CR), partial response (PR), or stable disease (SD) as determined by RECIST 1.1 response criteria. A CR is indicated by disappearance of all target and non target lesions. A PR is indicated by >=30% decrease in sum of longest diameter of target lesions with baseline as reference. SD is indicated by neither sufficient shrinkage to qualify for PR nor sufficient growth from nadir (>=20%) to indicate progression.

    Measured: From enrollment to best response while on study treatment; subjects remained on treatment until disease progression or death or unacceptable toxicity (subjects were on treatment for a median of 5.5 months)

  5. Duration of Response (DoR)

    Duration of Response (DoR) is defined as the duration of time from the first assessment that determined a CR or PR to the date of the first occurrence of progressive disease or death. Progression events and the censoring mechanism for DoR will be the same as described for PFS. DoR will be determined for each subject using the RECIST 1.1 criteria.

    Measured: From date of response to date of progression/death, or censored as described above; assessed for approximately 2 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 Jan 2017 (estimated)
  2. Study start12 Jun 2017
  3. Primary completion29 Jul 2021
  4. Study completion5 Aug 2022

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03018080
Sponsor's protocol ID
IRB00081370
Other IDs
00019078, LCI-BRE-H2N-PEPP-001
Acronym
PePPy
Status last verified
Jul 2023
First submitted
10 Jan 2017
Last updated
4 Aug 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L. Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol. 2016 Jul 20;34(21):2460-7. doi: 10.1200/JCO.2015.64.8931. Epub 2016 May 2.

    PubMed 27138582

  • Tan AR, Chai SJ, Robinson MM, Hellner LB, Gavini N, Sulai N, Turner JD, Atlas J, Graham DL, Induru RR, Kadakia KC, Vallabhanei GD, Heeke AL, Foureau DM, Fisher JG. A pilot study of paclitaxel plus pembrolizumab in patients with metastatic HER2-negative breast cancer (PePPy). Cancer Research. 2022; 82(4_Supplement): P2-14-03

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Paclitaxel in people with Breast - Female and Male Breast Cancer, run by Wake Forest University Health Sciences 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 26 inclusion and 25 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 4 Aug 2023. 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 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 13 Oct 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?

Number of Participants With at Least One Grade 3 or 4 Treatment-related Adverse Event (time frame: From enrollment to at least 30 days following cessation of study treatment. The median time on treatment was 5.5 months.). 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 NCT03018080, which also lists 2 linked publications.

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 4 Aug 2023.

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