Clinical trial NCT00821964: Topical Imiquimod and Abraxane in Treating Patients With Advanced Breast Cancer
Official title: Phase II Study of Topical Imiquimod and Weekly Abraxane for the Treatment of Breast Cancer Cutaneous Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Male Breast Cancer
Recurrent Breast Cancer
Skin Metastases
Stage IV Breast Cancer
Keywords: Breast Cancer
Stage IV
cream
topical
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-01-14
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is studying the side effects of giving topical imiquimod together with Abraxane (paclitaxel albumin-stabilized nanoparticle formulation) to see how well it works in treating patients with advanced breast cancer. Biological therapies, such as imiquimod, may stimulate the immune system to kill tumor cells. Drugs used in chemotherapy, such as Abraxane, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imiquimod together with Abraxane may kill more tumor cells.

Detailed description: PRIMARY OBJECTIVES:

I. To evaluate the safety of chemoimmunotherapy with topical imiquimod and Abraxane in breast cancer patients with recurrent chest wall disease or cutaneous metastasis.

II. To evaluate the anti-tumor effects of chemoimmunotherapy with topical imiquimod and Abraxane in breast cancer patients with recurrent chest wall disease or cutaneous metastasis.

SECONDARY OBJECTIVES:

I. To examine whether treatment with chemoimmunotherapy consisting of topical imiquimod and Abraxane augments endogenous tumor specific immunity.

II. To assess the effect of chemoimmunotherapy on circulating transforming growth factor (TGF)-beta levels.

OUTLINE:

Patients receive Abraxane intravenously (IV) over 30 minutes on days 1, 8, and 15 and apply topical imiquimod to cutaneous lesions once daily (QD) on days 1-4, 8-11, 15-18, and 22-25. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1, 4, 8, and 12 weeks.

Eligibility criteria: Inclusion Criteria:

* Patients with advanced stage refractory breast cancer
* Progressive or relapsed disease following standard therapy with chemotherapy and/or surgery, and/or radiation
* Patients must have measurable (bi-dimensional) chest wall disease and/or cutaneous metastatic lesions
* Patients must be at least 7 days from last chemotherapy and 30 days from local radiotherapy and/or systemic steroids
* Patients on bisphosphonates, trastuzumab, lapatinib and/or hormonal therapy are eligible
* White blood cell count \>= 1000/ul
* Absolute neutrophil count (ANC) \>= 1200/ul
* Platelets \> 75,000/ul
* Serum creatinine =\< 2.0 mg/dL, a creatinine clearance \> 60 ml/min
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2 X upper limit normal (ULN)
* Total bilirubin \< 2 X ULN
* Patients must have a Performance Status Score (Eastern Cooperative Oncology Group \[ECOG\] Scale) =\< 2
* Patients must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have a significant active concurrent medical illness precluding protocol treatment
* Men and women of reproductive ability must agree to contraceptive use during the study and for 1 month after imiquimod/Abraxane treatment is discontinued

Exclusion Criteria:

* Patients with prior allergic reaction to taxanes
* Patients with any clinically significant active autoimmune disease requiring active treatment with systemic steroids or other immunomodulators
* Pregnant or breast-feeding women
* Patients with peripheral neuropathy \>= Grade 2

Primary outcomes:
measure: Anti-tumor Effects of Imiquimod as Assessed by Modified World Health Organization (WHO) Criteria
timeFrame: Baseline and then every 4 weeks until week 24
measure: Safety and Systemic Toxicity as Assessed by a Review of Medical History, Physical Exam, Systems, Performance Status, and Clinical Labs (CBC and CMP)
timeFrame: Baseline and weeks 5, 9 13, 16, 20, and 24
measure: Pathologic Response by Immunohistochemical (IHC)as Assessed by Skin Punch Biopsy of the Target Lesion
timeFrame: Pre-and post-treatment
Secondary outcomes:
measure: Endogenous Immunity to Common Breast Tumor Antigens (HER2, IGFBP-2, Topoisomerase II-alpha, and p53) in Peripheral Blood as Assessed by IFN-gamma and ELISPOT Assay
timeFrame: Baseline and at weeks 13 and 24
measure: Incidence of Reduction of Serum TGF-beta Levels as Assessed by ELISA and Correlation With Th1 Adaptive Immunity and Clinical Response
timeFrame: Baseline and at weeks 13
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
name: Lupe Salazar
role: PRINCIPAL_INVESTIGATOR
References:
citation: Salazar LG, Lu H, Reichow JL, Childs JS, Coveler AL, Higgins DM, Waisman J, Allison KH, Dang Y, Disis ML. Topical Imiquimod Plus Nab-paclitaxel for Breast Cancer Cutaneous Metastases: A Phase 2 Clinical Trial. JAMA Oncol. 2017 Jul 1;3(7):969-973. doi: 10.1001/jamaoncol.2016.6007.