Radiotherapy in Combo With Chemo and Immunotherapy in Patients With PD-L1 Positive Metastatic TNBC

NCT05233696 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 21-3117.cc
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with locally advanced unresectable or metastatic programmed cell death ligand (PD-L1) positive triple negative breast cancer (TNBC) will be treated with radiation to one-four sites of metastasis amenable to radiation (sites of disease to be selected at the discretion of the treating radiation oncologist) followed by initiation of systemic therapy with pembrolizumab plus nab-paclitaxel/paclitaxel. Patients will be treated with pembrolizumab plus nab-paclitaxel/paclitaxel within 7 days of completion of radiation. Repeat imaging of all sites of disease will be performed every 9 weeks and response will be assessed according to RECIST 1.1.

Conditions

Triple Negative Breast Cancer; Locally Advanced Breast Cancer; Unresectable Breast Carcinoma; Metastatic Breast Cancer; PD-L1 Gene Mutation

Outcome Measures

Primary Outcomes (1)

• 1 year progression free survival rate

  To determine the efficacy of radiotherapy in combination with chemotherapy plus immunotherapy as defined by 1-year PFS rate in patients with PD-L1-positive metastatic TNBC.

  36 months

Secondary Outcomes (9)

• Rate of in-field tumor control

  36 months

• Determine overall response rate (ORR)

  36 months

• Determine clinical benefit rate (CBR)

  36 months

• Duration of response

  36 months

• Progression free survival

  36 months

Study Arms (1)

RT followed by nab-paclitaxel/paclitaxel plus pembrolizumab

EXPERIMENTAL

Nab-paclitaxel/paclitaxel plus pembrolizumab will be started within 7 days of completion of RT.

Drug: Nab-paclitaxel; Drug: Paclitaxel; Radiation: Radiation Therapy; Drug: Pembrolizumab

Interventions

Nab-paclitaxel DRUG

All patients are encouraged to receive nab-paclitaxel 100 mg/m2 IV D1 and D8 every 21 days (in combination with pembrolizumab) for at least 4-6 cycles per institutional standards and treating physicians' recommendations.

Also known as: Abraxane

RT followed by nab-paclitaxel/paclitaxel plus pembrolizumab

Paclitaxel DRUG

Paclitaxel can be substituted for nab-paclitaxel at the discretion of the treating physician 80 mg/m2 IV D1 and D8 every 21 days.

Also known as: Abraxane

RT followed by nab-paclitaxel/paclitaxel plus pembrolizumab

Radiation Therapy RADIATION

The treating radiation oncologist will select 1-4 sites of metastatic disease to target with radiation. All sites of disease may be targeted with radiation. Sites of metastatic disease planned to be biopsied should not be radiated.

RT followed by nab-paclitaxel/paclitaxel plus pembrolizumab

Pembrolizumab DRUG

Patients will receive pembrolizumab 200 mg D1 every 21 days.

Also known as: Keytruda

RT followed by nab-paclitaxel/paclitaxel plus pembrolizumab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision to sign and date the consent form including non-English speaking and non-reading participants.
• Stated willingness to comply with all study procedures and be available for the duration of the study.
• Male or female aged ≥ 18 years.
• Metastatic or locally advanced unresectable histologically documented TNBC as defined by absence of estrogen receptor (ER) and progesterone receptor (PR) expression and no HER2 amplification or over-expression by local pathology report.
• HER2 negativity is defined as either: in situ hybridization non-amplified (ratio of HER2 to CEP17 \< 2 or single probe average HER2 gene copy number \< 4 signals/cell OR IHC 0 or 1+).
• ER and PR negativity is defined as \< 1% positive by IHC.
• Treatment with \< 1 prior line of systemic therapy in the metastatic setting or adjuvant/neoadjuvant setting if metastatic recurrence within 12 months of treatment.
• Confirmed PD-L1 positive as defined by Combined Positive Score (CPS) \> 10% by a CLIA-certified lab
• At least one site of disease amenable to radiation therapy.
• Clinically appropriate for treatment with nab-paclitaxel/paclitaxel plus pembrolizumab in the opinion of the treating investigator.
• If the maximum number of non-biopsy subjects has accrued to the study, willingness to undergo 2 tumor biopsies and disease amenable to safe biopsy in the opinion of the treating investigator. NOTE: Tumor biopsies may be required, depending on the number of subjects who have agreed to undergo correlative studies.
• Life expectancy of \> 3 months per treating investigator.
• ECOG performance status ≤ 1.
• Baseline labs must meet the following criteria within 21 days of radiation initiation:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.

You may not qualify if:

• Any of the following interventions within the specified time frame prior to radiation:
• Radiation therapy within 21 days.
• Cytotoxic chemotherapy within 21 days (capecitabine within 14 days).
• Monoclonal antibodies within 21 days.
• Administration of an investigational agent that is not expected to be cleared prior to initiation of radiation.
• More than one prior line of chemotherapy in the locally advanced unresectable or metastatic setting.
• Prior treatment with a taxane in the metastatic setting. Prior taxane in the curative setting is allowed if treatment was completed ≥ 6 months prior to metastatic recurrence.
• Prior receipt of immune checkpoint inhibitor (PD-L1, PD-1 or CTLA-4 inhibitors) less than 12 mos from metastatic recurrence.
• Patients with active collagen vascular disease (CVD), specifically systemic lupus erythematosus or scleroderma. Patients with a history of CVD without evidence of active disease are eligible for enrollment at the discretion of the study PI.
• History of immunodeficiency, hypersensitivity to pembrolizumab or other medical contraindication to receipt of immunotherapy.
• Has active, or history of, pneumonitis requiring treatment with corticosteroids.
• Has a known history of active tuberculosis.
• Has a known history of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome - related illness (testing not required at screening).
• Has known active hepatitis B (hepatitis B surface antigen reactive) or hepatitis C (qualitative HCV RNA is detected) (testing not required at screening).
• Has received a live vaccine within 30 days prior to enrollment.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Cancer League of Colorado: collaborator

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Paclitaxel; Radiotherapy; pembrolizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Therapeutics

Study Officials

• Jennifer Diamond, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2022
• First Posted: February 10, 2022
• Study Start: January 4, 2022
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: December 6, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)