Standard of Care Chemotherapy Plus Pembrolizumab for Breast Cancer

NCT02734290 | Active Not Recruiting Phase 1 Results FDA Drug

• 1 other identifier: 16-001
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this study is to establish the safety and tolerability of pembrolizumab when administered in combination with either of two chemotherapy regimens (weekly paclitaxel or capecitabine) in unresectable/metastatic triple negative breast cancer (MTNBC) patients.

Conditions

Triple Negative Breast Cancer

Keywords

metastatic; Human epidermal growth factor receptor 2 (HER2) negative breast cancer; Estrogen Receptor (ER) negative breast cancer; Progesterone Receptor (PR) negative breast cancer; Immunotherapy; Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Treatment-Associated Adverse Events Requiring Discontinuation

  The count of participants who experienced serious adverse events and grade III/IV treatment-associated adverse events requiring discontinuation of pembrolizumab.

  6 weeks

• Number of Patients Who Complete Chemotherapy Without a Dose Delay of More Than 21 Days.

  The number of patients who complete 6 weeks of chemotherapy without requiring a dose delay of more than 21 days.

  6 weeks

Secondary Outcomes (1)

• Overall Response Rate

  12 weeks

Study Arms (2)

Arm A

EXPERIMENTAL

pembrolizumab + weekly paclitaxel

Drug: Pembrolizumab; Drug: Paclitaxel

Arm B

EXPERIMENTAL

pembrolizumab + capecitabine

Drug: Pembrolizumab; Drug: Capecitabine

Interventions

Pembrolizumab DRUG

Pembrolizumab 200mg every 3 weeks by IV infusion on Day 1 of each 3 week cycle

Also known as: Keytruda

Arm A; Arm B

Paclitaxel DRUG

Paclitaxel 80mg/m2 every 3 weeks by IV infusion on Days 1, 8, and 15 of each 3 week cycle

Also known as: Taxol

Arm A

Capecitabine DRUG

Capecitabine 2000mg every two weeks by mouth twice each day on days 1-7 of each 2 week cycle.

Also known as: Xeloda

Arm B

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be 18 years of age on day of signing informed consent.
• HER2-negative breast cancer (defined by immunohistochemistry (IHC) 0-1 (or) IHC 2 and in situ hybridization (ISH) HER2 / centromere on chromosome 17 (CEP17) \< 2.0);
• ER and PR-negative breast cancer (defined by IHC\<1%);
• Measurable metastatic or unresectable disease based on response evaluation criteria in solid tumours (RECIST) 1.1.
• Indicated for treatment with either weekly paclitaxel or oral capecitabine, as first or second-line chemotherapy in the metastatic/unresectable setting (as determined by the consenting investigator);
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained during screening. Archival tissue is acceptable if no intervening anti-neoplastic therapy has been administered, and if sufficient material is available for analysis (see section 8.0 for requirements);
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Demonstrate adequate organ function as defined by protocol defined lab values
• Female subjects of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential must avoid becoming pregnant while on treatment. Men must avoid fathering a child while on treatment.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or 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 a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study, Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. Denosumab is allowed.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy and alopecia are an exception to this criterion and may qualify for the study.
• Has received the assigned chemotherapy regimen previously in the metastatic setting, or has received the assigned chemotherapy regimen previously in the (neo)adjuvant setting within 12 months of consent;
• If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that progressed or required active treatment in the last 5 years.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• 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 history of/active pneumonitis requiring treatment with steroids or history of/active interstitial lung disease.
• Has an active infection requiring systemic therapy.
• 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.

Sponsors & Collaborators

• Providence Health & Services: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Providence Cancer Center

Portland, Oregon, 97213, United States

Location

Related Publications (2)

• Page DB, Pucilowska J, Chun B, Kim I, Sanchez K, Moxon N, Mellinger S, Wu Y, Koguchi Y, Conrad V, Redmond WL, Martel M, Sun Z, Campbell MB, Conlin A, Acheson A, Basho R, McAndrew P, El-Masry M, Park D, Bennetts L, Seitz RS, Nielsen TJ, McGregor K, Rajamanickam V, Bernard B, Urba WJ, McArthur HL. A phase Ib trial of pembrolizumab plus paclitaxel or flat-dose capecitabine in 1st/2nd line metastatic triple-negative breast cancer. NPJ Breast Cancer. 2023 Jun 21;9(1):53. doi: 10.1038/s41523-023-00541-2.

  PMID: 37344474 DERIVED

• Chun B, Pucilowska J, Chang S, Kim I, Nikitin B, Koguchi Y, Redmond WL, Bernard B, Rajamanickam V, Polaske N, Fields PA, Conrad V, Schmidt M, Urba WJ, Conlin AK, McArthur HL, Page DB. Changes in T-cell subsets and clonal repertoire during chemoimmunotherapy with pembrolizumab and paclitaxel or capecitabine for metastatic triple-negative breast cancer. J Immunother Cancer. 2022 Jan;10(1):e004033. doi: 10.1136/jitc-2021-004033.

  PMID: 35086949 DERIVED

Related Links

• Providence Cancer Center

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Neoplasm Metastasis; Breast Neoplasms

Interventions

pembrolizumab; Paclitaxel; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Dr. David B. Page
• Organization: Providence Portland Medical Center

david.page2@providence.org

5032156588

Study Officials

• David Page, MD

  Medical Oncologist

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2016
• First Posted: April 12, 2016
• Study Start: February 23, 2016
• Primary Completion: August 21, 2019
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 24, 2026
• Results First Posted: February 22, 2024

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)