Randomized Study of Combination Chemotherapy With or Without Focused Microwave Thermotherapy Before Surgery in Treating Women With Large Breast Cancer Tumors

NCT01204801 | Unknown Phase 3

• 1 other identifier: 102-00-301
• Study Type: interventional
• Target: 238
• Locations: 2 countries
• Sites: 2

Brief Summary

The purpose of this randomized Phase III study is to determine whether preoperative focused microwave heat treatment and chemotherapy combined are more effective than preoperative chemotherapy alone in the treatment of large breast cancer tumors in the intact breast. Combining heat with chemotherapy before surgery might shrink the tumor so that it can be removed in a breast conserving surgery (lumpectomy) instead of a mastectomy.

Conditions

Breast Cancer

Keywords

Cancer; Breast Cancer; Breast Tumor; Breast Neoplasm; Neoplasms by Site; Neoplasms; Breast Diseases; Breast Conserving Surgery; Breast Conservation; Partial Mastectomy; Lumpectomy; Mastectomy; Surgery; Neoadjuvant Therapy; Primary Therapy; Neoadjuvant Systemic Therapy; Thermotherapy; Fever Therapy; Hot Temperature; Hyperthermia; Hyperthermia, Therapeutic; Hyperthermia, Local; Hyperthermia, Induced; Therapeutic Hyperthermia; Microwave; Focused Microwave; Focused Microwave Thermotherapy; Minimally Invasive; Doxorubicin; Epirubicin; Epidoxirubicin; Immunosuppresive Agent; Immunologic Factors; Physiological Effects of Drugs; Chemotherapy; Drug Therapy; Pharmalogic Actions; Antirheumatic Agents; Therapeutic Uses; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloblative Agonists; Antibiotics, Antineoplastic; Anthracycline Agents

Outcome Measures

Primary Outcomes (1)

• Tumor Shrinkage (ultrasound)

  Evaluate the efficiency of preoperative focused microwave thermotherapy as an adjunct to chemotherapy to increase the ultrasound-measured absolute mean tumor percent shrinkage by volume over that achieved by SOC preoperative chemotherapy.

  Prior to Surgery, on average 4 months from the start of treatment

Secondary Outcomes (5)

• Conversion Rate to Breast Conservation (surgeon recommended)

  Prior to Mastectomy Recommendation, on average 4 months from the start of treatment

• Tumor Shrinkage (Clinical)

  Prior to Surgery, on average 4 months from the start of treatment

• Tumor Shrinkage (Mammography)

  Prior to Surgery, on average 4 months from the start of treatment

• Tumor Shrinkage (MRI)

  Prior to Surgery, on average 4 months from the start of treatment

• Tumor Necrosis (pathology)

  After Surgery, on average 5 months from the start of treatment

Study Arms (2)

Thermochemotherapy

EXPERIMENTAL

Preoperative Anthracycline Doxorubicin 60mg/m2 (or Epirubicin 100 mg/m2) + Standard of Care chemotherapy and drugs + Thermotherapy. Thermotherapy at first 3 chemotherapy treatments for Anthracycline chemotherapy nominally every 21±7 days plus Standard of Care chemotherapy.

Device: Focused Microwave Thermotherapy

Chemotherapy (control)

ACTIVE COMPARATOR

Preoperative Anthracycline Doxorubicin 60mg/m2 (or Epirubicin 100 mg/m2) + Standard of Care chemotherapy and drugs

Drug: Chemotherapy (control)

Interventions

Focused Microwave Thermotherapy DEVICE

Anthracycline Doxorubicin 60mg/m2 (or Epirubicin 100 mg/m2) + Standard of Care chemotherapy and drugs + Thermotherapy. Thermotherapy at first 3 chemotherapy treatments for Anthracycline chemotherapy nominally every 21±7 days plus Standard of Care chemotherapy. (A targeted tumor temperature of 44ºC (plus or minus 1.5ºC) and a targeted thermal dose of 80 equivalent treatment minutes (plus or minus 20 treatment minutes)). In the event that the targeted minimum cumulative thermal dose of 180 equivalent treatment minutes is not achieved in the first three treatments, an optional fourth thermotherapy treatment may be administered in combination with the fourth course of Anthracycline and standard of care chemotherapy. Standard of care (including breast imaging, drugs, and radiation) will be provided to all eligible subjects during and following the above study treatments.

Also known as: APA-1000 Focused Microwave Thermotherapy Device, Adriamycin

Thermochemotherapy

Chemotherapy (control) DRUG

Anthracycline Doxorubicin 60mg/m2 (or Epirubicin 100 mg/m2) + Standard of Care chemotherapy and drugs. Anthracycline chemotherapy nominally every 21±7 days. Standard of care (including breast imaging, drugs, and radiation) will be provided to all eligible subjects during and following the above study treatments.

Also known as: Adriamycin

Chemotherapy (control)

Eligibility Criteria

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

You may qualify if:

• Subjects must fulfill all of the following criteria to be eligible to participate in the study unless a specific waiver is requested by the investigator, agreed to by the sponsor, and documented for the study records. This protocol does not supersede Institutional IRB requirements for patient eligibility.
• Female subject must be 18 years of age or older.
• Subject must have adequate cognitive function to understand and sign the IRB/EC - approved informed consent prior to the performance of any study-specific procedure.
• The subject must be at no risk for pregnancy either postmenopausal for at least one year, surgically sterile (i.e. hysterectomy), using two forms of birth control one being barrier method or practicing abstinence throughout the length of the study. The subject must also have a negative serum pregnancy test prior to any study-specific procedure.
• Subject must have diagnosis by core biopsy of primary breast cancer, invasive ductal carcinoma or invasive lobular carcinoma, clinical tumor size 3.5 cm or greater, tumor classification T2 or T3, clinically node positive (N1, N2) or node negative (N0) by clinical exam, CT scan, or ultrasound, with distant metastasis (M1) or without distant metastasis (M0), with an indication for mastectomy.
• Primary tumor must be measurable on breast ultrasound (US).
• Primary tumor must be measurable by clinical exam.
• Subject is a candidate for mastectomy and is eligible for neoadjuvant treatment.
• Subject is a candidate for preoperative anthracycline-based combination chemotherapy.
• Subject has a life expectancy of 6 months or more.
• Karnofsky Score \> 70.

You may not qualify if:

• Subjects meeting any of the following criteria will be excluded from the study unless a specific waiver is requested by the investigator, agreed to by the sponsor, and documented appropriately for the study records. This protocol does not supersede Institutional IRB requirements for patient eligibility:
• Pregnant or lactating subject.
• Mentally unable to participate in the study successfully because they are unable to understand the informed consent or unable to comply with the required study procedures.
• Currently has breast implants.
• Bilateral breast cancer.
• Subjects with malignant breast tumors other than invasive ductal or invasive lobular carcinomas.
• Subject is a candidate for breast conservation at enrollment.
• Unable to tolerate prone position or breast compression.
• Clinically significant heart disease, pacemakers, or defibrillators.
• Bleeding disorders. Laboratory evidence of coagulopathy (PT, INR \> 1.5; PTT \> 1.5) or those who are receiving anticoagulants.
• Thrombocytopenia (platelet count less than 100,000/mm3).
• Renal insufficiency (BUN \> 30 mg/dlan/or serum creatinine \> 1.9 mg/dl).
• Liver disease (bilirubin \> 2.0 mg/dl and or \> 2 fold increase of transaminases).
• Diagnosis of cancer made by lumpectomy or incisional biopsy.
• Contraindications to chemotherapy.

Sponsors & Collaborators

• Medifocus, Inc.: lead

Study Sites (2)

Dr. William Dooley

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Ville-Marie Medical Centre

Montreal, Quebec, H3G 1L5, Canada

RECRUITING

Related Publications (2)

• Vargas HI; Dooley WC; Fenn AJ; Tomaselli MB; and Harness JK. Study of preoperative focused microwave phased array thermotherapy in combination with neoadjuvant anthracycline-based chemotherapy for large breast carcinomas. Cancer Therapy. 2007;5B:401-408. Available; http://www.cancer-therapy.org/CT5B/pdf/45._Vargas_et_al,_401-408.pdf. Accessed November 25, 2007. (background for protocol)

  BACKGROUND

• Dooley WC, Vargas HI, Fenn AJ, Tomaselli MB, Harness JK. Focused microwave thermotherapy for preoperative treatment of invasive breast cancer: a review of clinical studies. Ann Surg Oncol. 2010 Apr;17(4):1076-93. doi: 10.1245/s10434-009-0872-z. Epub 2009 Dec 22.

  PMID: 20033319 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms; Neoplasms by Site; Breast Diseases; Hyperthermia

Interventions

Drug Therapy; Doxorubicin

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heat Stress Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Therapeutics; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• William C. Dooley, MD

  University of Oklahoma

  PRINCIPAL INVESTIGATOR

• John Keyserlingk, MD

  Centre Medical Ville-Marie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2010
• First Posted: September 17, 2010
• Study Start: November 1, 2010
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: September 24, 2015

Record last verified: 2015-09

Locations

CA (1); US (1)