Topical Imiquimod and Abraxane in Treating Patients With Advanced Breast Cancer

NCT00821964 | Completed Phase 2 Results

• 4 other identifiers: 6578NCI-2010-00040R01CA138521131
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Male Breast Cancer; Recurrent Breast Cancer; Skin Metastases; Stage IV Breast Cancer

Keywords

Breast Cancer; Stage IV; cream; topical

Outcome Measures

Primary Outcomes (3)

• Anti-tumor Effects of Imiquimod as Assessed by Modified World Health Organization (WHO) Criteria

  Tumor responses will be determined using the sum of the products of the largest perpendicular dimensions. Target lesions will be evaluated by the following response criteria: complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Evaluation of target lesions per modified WHO response criteria: * Complete response (CR): complete clearance (100%) of target lesion(s) * Partial response (PR): ≥ 50% decrease in target lesion size * Stable disease (SD): \< 50% decrease in target lesion size * Progressive (PD): ≥ 25% increase in target lesion size Overall Response Rate (ORR) determined at end of study treatment which was 1 week after cycle #3, unless patient was withdrawn from study. If patient was withdrawn from study, then ORR was determined after their last cycle of treatment received.

  Baseline and then every 4 weeks until week 24

• Safety and Systemic Toxicity as Assessed by a Review of Medical History, Physical Exam, Systems, Performance Status, and Clinical Labs (CBC and CMP)

  Evaluated according to the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and monitoring of adverse events will be done per Food and Drug Administration (FDA) and National Cancer Institute (NCI) guidelines for the time frame below. Number of Participants with at Least 1 Adverse Event as Assessed by a Review of Medical History, Physical Exam, Systems, Performance Status, and Clinical Labs (CBC and CMP) under the following CTCAE categories: Constitutional (Fatigue) Neurological (Neuropathy (sensory or motor)) Cardiac (Arrhythemia) Pulmonary (Cough, Pharyngitis) GI (Constipation, Diarrhea, Mucositis, Vomiting) Dermatology (Ulceration, Hairloss/alopecia) Pain (Headache, other pain) Syndrome (Flu-like) Visual Changes Hearing/Auditory Edema Other (General) In addition they were asked the severity of the event so that a clinician could grade the event.

  Baseline and weeks 5, 9 13, 16, 20, and 24

• Pathologic Response by Immunohistochemical (IHC)as Assessed by Skin Punch Biopsy of the Target Lesion

  This is done by IHC staining reviewed by a pathologist. This is done by comparing the baseline to the post-treatment biopsy tissue. Yes equals absence of residual disease.

  Pre-and post-treatment

Secondary Outcomes (2)

• 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

  Baseline and at weeks 13 and 24

• Incidence of Reduction of Serum TGF-beta Levels as Assessed by ELISA and Correlation With Th1 Adaptive Immunity and Clinical Response

  Baseline and at weeks 13

Study Arms (1)

Treatment (biological therapy, chemo)

EXPERIMENTAL

Patients receive Abraxane IV over 30 minutes on days 1, 8, and 15 and apply topical imiquimod to cutaneous lesions 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.

Drug: imiquimod; Drug: Abraxane; Other: laboratory biomarker analysis; Genetic: RNA analysis; Other: immunoenzyme technique

Interventions

imiquimod DRUG

Given topically

Also known as: Aldara, IMQ, R 837

Treatment (biological therapy, chemo)

Abraxane DRUG

Given IV

Also known as: Albumin-Stabilized Nanoparticle Paclitaxel, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxel, Nanoparticle Paclitaxel, paclitaxel albumin-stabilized nanoparticle formulation

Treatment (biological therapy, chemo)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (biological therapy, chemo)

RNA analysis GENETIC

Correlative studies

Treatment (biological therapy, chemo)

immunoenzyme technique OTHER

Correlative studies

Also known as: immunoenzyme techniques

Treatment (biological therapy, chemo)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 28114604 DERIVED

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms

Interventions

Imiquimod; Albumin-Bound Paclitaxel; Taxes; 130-nm albumin-bound paclitaxel; Immunoenzyme Techniques

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; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Economics; Health Care Economics and Organizations; Immunoassay; Immunologic Techniques; Investigative Techniques; Immunohistochemistry; Molecular Probe Techniques

Results Point of Contact

• Title: Principal Investigator
• Organization: University of Washington

TrialTVG@medicine.washington.edu

Study Officials

• Lupe Salazar

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: January 13, 2009
• First Posted: January 14, 2009
• Study Start: December 1, 2008
• Primary Completion: November 1, 2012
• Study Completion: November 29, 2012
• Last Updated: January 2, 2018
• Results First Posted: June 28, 2017

Record last verified: 2017-12

Locations

US (1)