Phase II PEMBROLIZUMAB + PALLIATIVE RADIOTHERAPY IN BC

NCT03051672 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 16-588
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Metastatic Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (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.

  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)

• Incidence of Grade 4 Treatment-Related Toxicity

  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.

• Median Progression-free Survival (PFS)

  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.

• Median Overall Survival (OS)

  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.

Study Arms (1)

Pembrolizumab With Radiation

EXPERIMENTAL

pembrolizumab : 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

Drug: Pembrolizumab; Radiation: Palliative radiotherapy

Interventions

Pembrolizumab DRUG

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.

Also known as: Keytruda

Pembrolizumab With Radiation

Palliative radiotherapy RADIATION

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

Pembrolizumab With Radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• 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.

  PMID: 32113750 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Dr. Sara Tolaney
• Organization: Dana-Farber Cancer Institute

sara_tolaney@dfci.harvard.edu

6176323800

Study Officials

• Sara Tolaney, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 8, 2017
• First Posted: February 14, 2017
• Study Start: May 22, 2017
• Primary Completion: September 4, 2018
• Study Completion: January 11, 2019
• Last Updated: April 27, 2021
• Results First Posted: April 27, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)