Trial of Partial Breast Irradiation With Various Concurrent Chemotherapy Regimens

NCT00681993 | Completed DMC

• 2 other identifiers: J0805IRB00063221
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Breast conserving therapy, (BCT), which consists of wide local excision of the tumor followed by 6 weeks of whole breast irradiation, (WBI), is integral to the management of breast cancer. Evidence now suggests that WBI may not be necessary and treatment to the involved area only, partial breast irradiation, (PBI), may suffice. PBI can be achieved by interstitial or intracavitary brachytherapy, intra-op, or post op external beam radiation therapy. The feasibility, toxicity and efficacy of PBI are currently being studied in both the U.S. and Europe. Review of smaller studies suggests that PBI will prove to be comparable to WBI. Chemotherapy combined with radiation has been shown to increase local control in BCT when compared to radiation alone. However there is little data on how sequencing or timing of these therapies with respect to one another affect outcome. As a result there is no consensus about the optimal combination. There are real and potential benefits to concurrent chemo-radiation therapy. Concurrent therapy 1) allows both treatments to start closer to surgery, theoretically maximizing the benefits of each modality; 2) shortens the overall treatment program; and 3) may also improve local control via chemo-sensitization of residual cancer cells. However, concurrent chemotherapy and WBI have been associated with prohibitive skin toxicity. Since less breast tissue is treated with PBI, this skin toxicity may no longer be prohibitive. We have shown in J0381 that PBI and concurrent dose dense AC is safe. As a follow-up, we propose a phase I/II trial addressing the toxicity and efficacy associated with PBI delivered concurrently with various chemotherapy regimens.

Conditions

Breast Cancer

Keywords

cosmetic; effect; breast; irradiation; concurrent; chemotherapy; potential acute; late skin; subcutaneous toxicities

Outcome Measures

Primary Outcomes (3)

• Acute skin toxicities of partial breast irradiation concurrent with chemotherapy (PBIC)

  Acute Skin toxicity will be scored on a scale ranging from 0-4, where a higher score reflects more severe toxicity: 0= no change; 1= follicular, fain or dull erythema/epilation/dry/desquamation/decreased swelling; 2= tender or bright erythemal patchy moist desquamation/moderate edema; 3= confluent moist desquamation other than skin folds, pitting edema; 4= ulceration, hemorrhage, necrosis.

  up to 5 years post-intervention

• Late skin toxicities of PBIC

  Late Skin toxicity will be scored on a scale ranging from 0-4, where a higher score reflects more severe toxicity: 0= none; 1= slight atrophy, pigmentation change, some hair loss; 2= patchy atrophy, moderate telangiectasias, total hair loss; 3= marked atrophy, gross telangiectasias; 4= ulceration

  up to 5 years post-intervention

• Subcutaneous tissue toxicities of PBIC

  Subcutaneous tissue toxicity will be scored on a scale ranging from 0-4, where a higher score reflects more severe toxicity: 0= none; 1= slight induration (fibrosis) and loss of subcutaneous fat; 2= moderate fibrosis but asymptomatic; slight field contracture; \<10% linear reduction; 3= severe induration and loss subcutaneous tissue; field contracture \>10% linear reduction; 4= necrosis

  up to 5 years post-intervention

Secondary Outcomes (2)

• Cosmetic effect of PBIC

  up to 5 years post-intervention

• Local control rate of patients treated with PBIC.

  up to 5 years post-intervention

Study Arms (5)

Standard ddAC chemotherapy with concurrent radiation therapy

ACTIVE COMPARATOR

Standard dose-dense Adriamycin and Cyclophosphamide (ddAC) chemotherapy and concurrent radiation therapy (RT)

Other: Standard Dose Dense Doxorubucin and Cyclophosphamide

Standard AC chemotherapy with concurrent RT

ACTIVE COMPARATOR

Standard Adriamycin and Cyclophosphamide (AC) chemotherapy and concurrent radiation therapy

Other: Standard Doxorubucin and Cyclophosphamide

Standard TCarbo H chemotherapy with concurrent RT

ACTIVE COMPARATOR

Standard Taxotere, Carboplatin and Herceptin (TCarbo H) chemotherapy and concurrent radiation therapy

Other: Standard Docetaxel, Carboplatin, and Herceptin

Standard TAC chemotherapy with concurrent RT

ACTIVE COMPARATOR

Standard Taxotere, Adriamycin and Cyclophosphamide (TAC) chemotherapy with concurrent radiation therapy

Other: Standard Docetaxel, Doxorubucin and Cyclophosphamide

Standard TC chemotherapy with concurrent RT

ACTIVE COMPARATOR

Standard Taxotere and Cyclophosphamide (TC) chemotherapy with concurrent radiation therapy

Other: Standard Docetaxel and Cyclophosphamide

Interventions

Standard Dose Dense Doxorubucin and Cyclophosphamide OTHER

4 cycles of Standard Dose-Dense Doxorubucin and Cyclophosphamide and concurrent radiation therapy at a dose of 270 cGy per fraction for 15 fractions to a total dose of 40.5 Gy. Treatments will be given Monday through Friday for three weeks. Radiation therapy may start 7 days before, but no later than 7 days after, day 1 of cycle 1 of chemotherapy (C1D1).

Also known as: Doxorubucin (Adriamycin, Rubex, Adriamycin RDF, Adriamycin PFS,, hydroxydaunorubicin, hydroxydaunomycin), Cyclophosphamide (Cytoxan, Neosar, CTX, CPM)

Standard ddAC chemotherapy with concurrent radiation therapy

Standard Doxorubucin and Cyclophosphamide OTHER

4 cycles of Standard Dose Doxorubucin and Cyclophosphamide and concurrent radiation therapy at a dose of 270 cGy per fraction for 15 fractions to a total dose of 40.5 Gy. Treatments will be given Monday through Friday for three weeks. Radiation therapy may start 7 days before, but no later than 7 days after, day 1 of cycle 1 of chemotherapy (C1D1).

Also known as: Doxorubucin (Adriamycin, Rubex, Adriamycin RDF, Adriamycin PFS,, hydroxydaunorubicin, hydroxydaunomycin), Cyclophosphamide (Cytoxan, Neosar, CTX, CPM)

Standard AC chemotherapy with concurrent RT

Standard Docetaxel, Carboplatin, and Herceptin OTHER

6 cycles of Standard Docetaxel, Carboplatin and Herceptin chemotherapy with concurrent radiation therapy at a dose of 270 cGy per fraction for 15 fractions to a total dose of 40.5 Gy. Treatments will be given Monday through Friday for three weeks. Radiation therapy may start 7 days before, but no later than 7 days after, day 1 of cycle 1 of chemotherapy (C1D1).

Also known as: Docetaxel (Taxotere), Carboplatin (CBDCA, Paraplatin, JM-8), Herceptin (Trastuzumab, RhuMAb HER2, HER2/neu, anti-HER2 humanized, monoclonal antibody)

Standard TCarbo H chemotherapy with concurrent RT

Standard Docetaxel, Doxorubucin and Cyclophosphamide OTHER

3 cycles of Standard Docetaxel, Doxorubucin and Cyclophosphamide chemotherapy with concurrent radiation therapy at a dose of 270 cGy per fraction for 15 fractions to a total dose of 40.5 Gy. Treatments will be given Monday through Friday for three weeks. Radiation therapy may start 7 days before, but no later than 7 days after, day 1 of cycle 1 of chemotherapy (C1D1).

Also known as: Docetaxel (Taxotere), Cyclophosphamide (Cytoxan, Neosar, CTX, CPM)

Standard TAC chemotherapy with concurrent RT

Standard Docetaxel and Cyclophosphamide OTHER

4 cycles of Standard Docetaxel and Cyclophosphamide chemotherapy with concurrent radiation therapy at a dose of 270 cGy per fraction for 15 fractions to a total dose of 40.5 Gy. Treatments will be given Monday through Friday for three weeks. Radiation therapy may start 7 days before, but no later than 7 days after, day 1 of cycle 1 of chemotherapy (C1D1).

Also known as: Docetaxel (Taxotere), Cyclophosphamide (Cytoxan, Neosar, CTX, CPM)

Standard TC chemotherapy with concurrent RT

Eligibility Criteria

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

Eligibility Criteria: Each of the criteria in the following section must be met in order for a patient to be considered eligible for registration. * Patient must be older than 18 years of age * Patients must have histologically confirmed (by routine H\&E staining) adenocarcinoma of the breast, with the primary tumor \< 4 cm and 0 - 3 positive axillary lymph nodes (pathologic T1-2, pathologic N0 -N1, M0). Patients with squamous carcinomas or sarcomas of the breast cancer are NOT eligible. * Patient must have a history and physical within six weeks prior to the start of any protocol therapy. * Patient must have had a bilateral mammogram prior to surgery. * Patients must have undergone a segmental mastectomy (SM) with a level I and ll axillary dissection or sentinel lymph node biopsy. Surgical margins at time of SM must be negative (\> or = 2 mm) for both invasive carcinoma and for non-invasive ductal carcinoma. Patients who have post-operative margins which are negative but less than 2mm will be considered eligible if the surgeon states that the margin in question could not be improved. * Patient must have a Medical Oncology consult and be recommended to receive one of the following regimens: Cyclophosphamide and Doxorubicin (AC); Taxotere, Doxorubicin and Cyclophosphamide (TAC); Taxotere and Cyclophosphamide (TC) or Taxotere, Carboplatin and Trastuzumab (TCH) prior to registration. The use of additional chemotherapy, hormonal therapy or Trastuzumab after the initial regimen is at the discretion of the medical oncologist. * Patients must be registered such that radiation therapy begins no sooner than 7 days prior to, but no later than 7 days after, day 1 of cycle 1 (C1D1). Patient must start chemotherapy and radiation less than 14 weeks from the last breast surgical procedure. * Patients must NOT have received any neo adjuvant chemo or hormonal therapy for the current cancer. * Patients must have a performance status 0 or 1 by ECOG criteria * Patients must not have received prior radiation therapy to the involved breast at any time for any reason. * Any patient with active local-regional disease prior to registration is not eligible. * No other prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer from which the patient has been disease-free for 5 years. * Patients must not be pregnant due to the potential for fetal harm as a result of this treatment regimen. Women of child-bearing potential must use effective non hormonal contraception while undergoing radiation therapy. Women of child-bearing potential must also have a negative pregnancy test within six weeks prior to start of protocol therapy. * Patients must not have a serious medical or psychiatric illness which prevents informed consent or compliance with treatment. * All patients must be informed of the investigational nature of this study and given written informed consent in accordance with institutional and federal guidelines.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Breast Cancer Research Foundation: collaborator

Study Sites (1)

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide; Doxorubicin; carboxypeptidase M; Carboplatin; Trastuzumab; Docetaxel; Receptor Protein-Tyrosine Kinases; Antibodies, Monoclonal

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Protein-Tyrosine Kinases; Protein Kinases; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Intracellular Signaling Peptides and Proteins; Receptors, Cell Surface; Membrane Proteins

Study Officials

• Richard Zellars, M.D.

  The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

• Amit Shah, M.D.

  York Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2008
• First Posted: May 21, 2008
• Study Start: April 1, 2008
• Primary Completion: June 1, 2012
• Study Completion: March 4, 2016
• Last Updated: January 22, 2019

Record last verified: 2019-01

Locations

US (1)