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Metastatic Breast CancerPhase 2NCT03051672

Phase II PEMBROLIZUMAB + PALLIATIVE RADIOTHERAPY IN BC

A Phase 2 study testing Pembrolizumab and Palliative radiotherapy in people with Metastatic Breast Cancer, run by Dana-Farber Cancer Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This research study is studying radiation therapy in combination with an immunotherapy as a possible treatment for metastatic hormone receptor (HR) positive, HER2-negative breast cancer. The interventions involved in this study are: Palliative Radiotherapy Pembrolizumab Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
Pembrolizumab and Palliative radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
22 May 2017to 11 Jan 2019
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

  • Participants must have histologically or cytologically confirmed invasive breast cancer, with metastatic disease. Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.
  • Invasive disease must have been tested for ER, PR and HER2. Participants must have hormone-receptor positive, HER2-negative breast cancer defined as:
  • ER>1% or PR>1%
  • HER2-negative per ASCO CAP guidelines, 2013 [Wolff et al., 2013]
  • Participant must be a candidate for palliative radiation treatment to at least one bone, lymph node, or soft tissue lesion. Radiation of visceral lesions (such as lung or hepatic lesions) is not permitted.
  • Participant must have measurable disease outside the field of radiation as defined by RECIST 1.1.
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  • If tumor is accessible and outside the field of radiation, the participant must be willing to undergo a research biopsy at baseline and after 2 cycles of pembrolizumab. Participants for whom newly-obtained samples cannot be provided (e.g. inaccessible or safety concern) must be willing to submit an archival specimen.
  • Prior systemic therapy:
  • Participant must be at least 14 days from the last dose of prior chemotherapy, endocrine therapy, biological agents (including small molecule targeted therapy) or any investigational drug product with adequate recovery of toxicity to baseline, or grade 1(with the exception of alopecia and hot flashes) at the time of registration.
  • There is no limit to the number of prior lines of therapy, including endocrine or cytotoxic agents. Systemic treatment naive patients for metastatic disease are also eligible.
  • Participants may initiate or continue bisphosphonate therapy on study.
  • Continuation of ovarian suppression is allowed.
  • Prior radiation therapy:
  • Patients must be at least 3 months from prior radiation therapy
  • Re-irradiation of the same field is not allowed
  • Concurrent administration of other cancer specific therapy during the course of this study is not allowed.
  • The subject is ≥18 years old
  • ECOG performance status ≤1 (See Appendix A for details)
  • Participants must have normal organ and marrow function as defined below:
  • absolute neutrophil count ≥1,500/mcL
  • platelets ≥100,000/mcL
  • hemoglobin ≥ 8 g/dl
  • total bilirubin ≤1.5 × institutional upper limit of normal (ULN)
  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN or ≤ 5 × institutional ULN for participants with documented liver metastases
  • creatinine ≤1.5 ×within normal institutional ULN (or 2.0 x ULN in patients with documented Gilbert's Syndrome) OR creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional ULN.
  • International normalized ratio (INR) or Prothrombin Time (PT) <1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • Activated Partial Thromboplastin Time (aPTT) <1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • Female subjects of childbearing potential must have a negative pregnancy test at screening
  • Female and male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in section 5.4.1. Contraception is required starting with the first dose of study medication through 120 days after the last dose of study medication Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Resolution of all chemotherapy-related or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy (≤ Grade 2) and alopecia.
  • The subject is capable of understanding and complying with the protocol and has signed the informed consent document

Who cannot join

  • Participants who are receiving any other investigational agents.
  • Previous treatment with any anti-PD-1, PD-L1, or PD-L2 agent.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab.
  • Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms. Participants with previously diagnosed brain metastases are eligible if they have:
  • completed treatment (whole brain radiotherapy, radiosurgery, or a combination) at least 3 months prior to trial therapy initiation,
  • are neurologically stable, and
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  • have recovered from effects of radiotherapy or surgery. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for ≥2 weeks before prior to registration.
  • Radiologic or clinical evidence of Spinal Cord Compression.
  • Spinal Instability Neoplastic Score ≥ 7 unless lesion reviewed by a neurosurgical service and considered stable.
  • Participants with bone lesions requiring surgical fixation to provide mechanical stability are ineligible. Participants with previously fixed lesions are allowed.
  • The participant has an uncontrolled intercurrent illness, including, but not limited to uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, congestive heart failure-New York Heart Association Class III or IV, active ischemic heart disease, myocardial infarction within the previous six months, uncontrolled diabetes mellitus, gastric or duodenal ulceration diagnosed within the previous 6 months, severe malnutrition or psychiatric illness/social situations that would limit compliance with study requirements.
  • Clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/QTc ([QT interval/corrected QT interval], eg, a repeated demonstration of a QTc interval >500 ms).
  • Participant has a medical condition that requires chronic systemic steroid therapy or on any other form of immunosuppressive medication. For example, patients with autoimmune disease that requires systemic steroids or immunosuppression agents should be excluded. 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 history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Has a history of interstitial lung disease.
  • The participant is known to be positive for the human immunodeficiency virus (HIV), HepBsAg, or HCV RNA. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Pembrolizumab.
  • Individuals with a history of different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years or are deemed by the investigator to be at low risk for recurrence of that malignancy.
  • Has received a live vaccine within 30 days of planned start of study therapy.
  • The participant is pregnant or breast-feeding

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Phase II Study Of Pembrolizumab In Combination With Palliative Radiotherapy For Metastatic Hormone Receptor Positive Breast Cancer

This research study is studying radiation therapy in combination with an immunotherapy as a possible treatment for metastatic hormone receptor (HR) positive, HER2-negative breast cancer.

The interventions involved in this study are:

  • Palliative Radiotherapy
  • Pembrolizumab
Read the detailed description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

In this research study, the investigators are evaluating the safety and effectiveness of palliative radiotherapy ("radiation therapy") in combination with pembrolizumab in HR-positive, HER2-negative breast cancer. This study is designed to test how well radiation therapy in combination with pembrolizumab treats this type of cancer.

The FDA has approved radiation therapy as a treatment option for this type of breast cancer.

The FDA (the U.S. Food and Drug Administration) has not approved pembrolizumab for this specific disease but it has been approved in the United Sates for other types of cancer.

Pembrolizumab is a drug that may treat cancer by working with the immune system. The immune system is the body's natural defense against disease. The immune system sends types of cells called "T cells" throughout the body to detect and fight infections and diseases, including cancer. For some types of cancer, the T cells do not work as they should and are prevented from attacking the tumors. Pembrolizumab is thought to work by blocking a protein in the T cells called PD-1 ("programmed death 1"), which then allows these cells and other parts of the immune system to attack tumors.

The combination of pembrolizumab and radiation therapy is investigational. The study drug and radiation therapy, when given separately, work in different waysto help stop the cancer cells from growing and spreading. However, it is not known if giving the study drug and radiation therapy at the same time will have a better anti-cancer effect than giving each treatment on its own.

Being tested
Pembrolizumab, Palliative radiotherapy
Keywords
Breast Cancer
Medical subject headings
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

    Pembrolizumab (formerly MK-3475) is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD1 and its ligands, PD-L1 and PD-L2.

  • Palliative radiotherapyRadiation

    Palliative radiotherapy aims to shrink cancer, slow down its growth or control symptoms.

Study groups in NCT03051672
Study groupRoleWhat they receive
Pembrolizumab With RadiationExperimentalpembrolizumab : 200 mg intravenously 2 to 7 days prior to radiotherapy (RT) and on day 1 of repeating 21-day cycles. Treatment up to 35 cycles. Palliative radiation: a total dose of 20 Gy in 5 fractions
Receives: Drug: Pembrolizumab; Radiation: Palliative radiotherapy

What is being measured

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

  1. Objective Response Rate

    The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) outside the field of radiation based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Tumor measurements are repeated every 6 weeks for the first 24 weeks and then every 9 weeks thereafter. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was 1 cycle. Response was evaluated up to 3 months.

Secondary outcomes (3)

  1. Incidence of Grade 4 Treatment-Related Toxicity

    All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv3 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation.

    Measured: Tumor measurements are repeated every 6 weeks for the first 24 weeks and then every 9 weeks thereafter. Treatment continued until disease progression or unacceptable toxicity. Response was evaluated up to 3 months.

  2. Median Progression-free Survival (PFS)

    Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

    Measured: Tumor measurements are repeated every 6 weeks for the first 24 weeks and then every 9 weeks thereafter. Treatment continued until disease progression or unacceptable toxicity. The maximum follow-up time is 3 months.

  3. Median Overall Survival (OS)

    OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

    Measured: Tumor measurements are repeated every 6 weeks for the first 24 weeks and then every 9 weeks thereafter. Treatment continued until disease progression or unacceptable toxicity. The maximum follow-up time is 13 months.

Timeline

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

  1. First posted14 Feb 2017
  2. Study start22 May 2017
  3. Primary completion4 Sep 2018
  4. Study completion11 Jan 2019

Why it stopped: Based on two-stage design, the study ended at stage 1 with no evidence of promise based on pre-specified decision rule.

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
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03051672
Sponsor's protocol ID
16-588
Status last verified
Mar 2021
First submitted
8 Feb 2017
Last updated
27 Apr 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Barroso-Sousa R, Krop IE, Trippa L, Tan-Wasielewski Z, Li T, Osmani W, Andrews C, Dillon D, Richardson ET 3rd, Pastorello RG, Winer EP, Mittendorf EA, Bellon JR, Schoenfeld JD, Tolaney SM. A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer. Clin Breast Cancer. 2020 Jun;20(3):238-245. doi: 10.1016/j.clbc.2020.01.012. Epub 2020 Jan 30.

    PubMed 32113750

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Palliative radiotherapy in people with Metastatic Breast Cancer, run by Dana-Farber Cancer Institute 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 31 inclusion and 19 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: stopped early, as of the sponsor's last update on 27 Apr 2021. 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 27 Apr 2021). 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?

Objective Response Rate (time frame: Tumor measurements are repeated every 6 weeks for the first 24 weeks and then every 9 weeks thereafter. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was 1 cycle. Response was evaluated up to 3 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 NCT03051672, 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 27 Apr 2021.

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