Epicutaneous Cryoimmunotherapy Combined With Pembrolizumab for Cutaneous Metastatic Breast Cancer

NCT03982004 | Terminated Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 201911047
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to look at the safety and side effects of combining the drug pembrolizumab with imiquimod, GM-CSF, and cryotherapy to treat breast cancer that includes skin lesions.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability as measured by rate of treatment emergent grade 3 or higher toxicities

  -NCI Common terminology criteria for adverse events (CTCAE v5.0) will be used to grade toxicities

  From beginning of treatment through 90 days following completion of treatment or 30 days following completion of treatment if the participant initiates new therapy (whichever is earlier)

Secondary Outcomes (9)

• Objective response rate (ORR) as measured by RECIST 1.1

  Baseline and 18 weeks

• Progression-free survival (PFS)

  2 years

• Change from baseline to week 3 in the number of tumor infiltrating lymphocytes after epicutaneous cryoimmunotherapy

  Baseline and week 3

• Change from baseline to week 9 in the number of tumor infiltrating lymphocytes after epicutaenous cryoimmunotherapy plus pemrolizumab

  Baseline and week 9

• Change from baseline to 18 weeks in the number of tumor cells

  Baseline and 18 weeks

Study Arms (1)

Epicutaneous cryoimmunotherapy+imiquimod+pembrolizumab+GM-CSF

EXPERIMENTAL

* Epicutaneous cryoimmunotherapy treatments (6 total) during weeks 1-15 (every 2 weeks for the first 2 treatments, then every 3 weeks until week 15) * Topical imiquimod will be applied 5 days per week (5 days on, 2 days off from weeks 1-15) * Pembrolizumab will be given every 3 weeks for a minimum of 4 cycles starting at Week 3 until disease progression or unacceptable toxicity. * Intra-lesional GM-CSF 250 mcg every 2 weeks x 2 doses then every 3 weeks for 3 doses

Device: Epicutaneous cryoimmunotherapy; Drug: Topical imiquimod; Drug: Pembrolizumab; Other: Dermatologic Quality of Life Index; Other: Functional Assessment of Cancer Therapy; Drug: Intra-lesional GM-CSF; Device: Cry-AC; Procedure: Cutaneous tumor biopsy; Procedure: Peripheral blood draw for research

Interventions

Epicutaneous cryoimmunotherapy DEVICE

Epicutaneous cryoimmunotherapy (EC) treatment includes liquid nitrogen cryotherapy applied for 10 seconds x 2 freeze-thaw cycles. Four treatment areas will be chosen at each treatment.

Epicutaneous cryoimmunotherapy+imiquimod+pembrolizumab+GM-CSF

Topical imiquimod DRUG

Patients will apply the cream directly over the treatment areas and can use up to one packet per day (covers approximately 5 cm x 5 cm).

Epicutaneous cryoimmunotherapy+imiquimod+pembrolizumab+GM-CSF

Pembrolizumab DRUG

Pembrolizumab 200 mg will be administered as a 30 minute IV infusion

Also known as: Keytruda

Epicutaneous cryoimmunotherapy+imiquimod+pembrolizumab+GM-CSF

Dermatologic Quality of Life Index OTHER

* 10 questions about how much skin problems has affected the participant's life over the past week * The scoring of each question is as follows: very much = 3, a lot = 2, a little = 1, not at all = 0, not relevant = 0, and question #7 'prevented work or studying' = 3 * The DLQI is calculated by summing the score of each question resulting in a max of 30 and min of 0. The higher the score, the more quality of life is impaired.

Also known as: DLQI

Epicutaneous cryoimmunotherapy+imiquimod+pembrolizumab+GM-CSF

Functional Assessment of Cancer Therapy OTHER

* 5 subscales (physical well-being, social/family well-being, emotional well-being, functional well-being, and additional concerns) * Answers ranging from 0=Not at all to 4 = very much * Each item is rated on a 5-point Likert scale. * The higher the score on the social/family well-being and functional well-being indicate higher quality of life * The lower the score on physical well-being, emotional well-being, and additional concerns indicate higher quality of life

Also known as: FACT-B

Epicutaneous cryoimmunotherapy+imiquimod+pembrolizumab+GM-CSF

Intra-lesional GM-CSF DRUG

250 mcg every 2 weeks x 3 doses then every 3 weeks for 3 doses

Epicutaneous cryoimmunotherapy+imiquimod+pembrolizumab+GM-CSF

Cry-AC DEVICE

-Device used to give the cryoimmunotherapy

Epicutaneous cryoimmunotherapy+imiquimod+pembrolizumab+GM-CSF

Cutaneous tumor biopsy PROCEDURE

-Baseline, week 3 (prior to 1st dose of pembrolizumab), week 9, and at week 18. An optional biopsy can be obtained at the time of disease progression.

Epicutaneous cryoimmunotherapy+imiquimod+pembrolizumab+GM-CSF

Peripheral blood draw for research PROCEDURE

-Baseline, week 3 (prior to 1st dose of pembrolizumab), week 9, and at week 18. An optional biopsy can be obtained at the time of disease progression.

Epicutaneous cryoimmunotherapy+imiquimod+pembrolizumab+GM-CSF

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed locally advanced unresectable or metastatic breast cancer (any ER, PR, HER2) with biopsy-proven cutaneous metastasis
• Disease progression in skin and/or systemic lesions after one or more lines of therapy as follows:
• HER2 positive patients must have been previously treated with Pertuzumab, Trastuzumab, and T-DM1, with at least one of them in the metastatic setting
• ER positive patients must have had at least one prior line of endocrine therapy in the metastatic setting.
• Prior treatment could include:
• Chemotherapy
• Endocrine therapy for patients with ER+ disease (including aromatase inhibitors, selective estrogen receptor degraders/modulators, mTOR inhibitors, CDK 4/6 inhibitors)
• HER2-targeted therapies for HER2+ disease (including monoclonal antibodies, antibody drug conjugates, tyrosine kinase inhibitors) Note: there is no limit to the number of prior therapy lines for unresectable or metastatic breast cancer.
• Concurrent treatment is allowed as follows:
• Patients with stable systemic disease may continue on concurrent maintenance therapy provided there is no anticipated need to change therapy during the study period.
• Note: for these patients, the cutaneous lesions must either be progressing or stable for at least 2 months (i.e. not responding to current therapy).
• Patients changing to a new systemic therapy must start treatment at least 2 weeks before the planned start of study treatment.
• Have measurable disease based on RECIST 1.1.
• Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Patients with non-measurable or measurable systemic disease are eligible.

You may not qualify if:

• Has large, ulcerated, bulky tumors (defined as total volume greater than 4 x 4 x 4 cm\^3 with \> 50% ulceration).
• Has life expectancy of \< 6 months.
• Prior treatment with the following:
• Any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137).
• Radiotherapy within 2 weeks of start of study treatment. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
• Investigational agents or devices within 4 weeks prior to anticipated study treatment start date Note: Participants must have recovered from all AEs due to a previous therapies to ≤ grade 1 or baseline. Subjects with ≤ Grade 2 neuropathy are eligible if per treating physician the neuropathy symptoms are stable. Patients must have completed any corticosteroids for treatment-related toxicities. Patients who developed radiation pneumonitis are not eligible.
• Note: If subject had recent surgery, they must have recovered adequately from the toxicity and/or complications from the intervention in the opinion of the treating investigator prior to starting therapy
• Has severe hypersensitivity (≥ grade 3) to pembrolizumab or any of its excipients.
• Has a known additional malignancy that is progressing or requires active treatment within the past 3 years. Note: participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer) that have undergone potentially curative therapy are not excluded.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Subjects with previously treated brain metastases may participate provided they are radiologically stable for at least 4 weeks and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Note: Patients with stable brain metastases must have stable brain imaging within 28 days prior to first dose of study treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) 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)
• 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). Note: Replacement therapy (e.g., thyroxin, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Imiquimod; pembrolizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Mateusz Opyrchal, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2019
• First Posted: June 11, 2019
• Study Start: September 14, 2020
• Primary Completion: March 3, 2021
• Study Completion: March 3, 2021
• Last Updated: June 21, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)