A Randomized Phase III Trial of the Value of Early Local Therapy for the Intact Primary Tumor in Patients With Metastatic Breast Cancer
- To evaluate whether early local therapy comprising surgery of intact primary disease
compared to local palliative therapy only in patients with stage IV breast cancer,
whose disease does not progress during initial optimal systemic therapy, will result in
- To compare the time to uncontrolled chest wall disease between patients treated with
- To determine whether there is a difference in health-related quality-of-life (HRQOL)
between patients treated with these regimens.
- To determine whether the absolute value of circulating tumor cells (CTC) burden at 6
months following randomization (time +6) will be lower in the palliative therapy arm
than in early local therapy arm, and whether this value is inversely related to
survival (lower CTC, longer survival).
- To collect tumor and blood specimens for future exploration of the biological
interactions between the primary tumor and metastatic lesions and the effect of primary
OUTLINE: This is a multicenter study. Patients are stratified according to hormone receptor
and treatment plan (ER+ or PR+, HER2-, endocrine therapy alone vs ER+ or PR+, and HER2-,
chemotherapy and/or endocrine therapy vs ER- or PR-, and HER2- vs HER2+), and number of
involved organ systems with distant disease (regional nodes in the axillary,
supraclavicular, and internal mammary locations are not considered distant sites) (1 vs >
1). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive standard palliative therapy, if needed, to address symptoms
such as tumor ulceration, pain, bulky adenopathy causing arm symptoms, and other
similar situations. Therapy may consist of radiotherapy alone, surgery alone, or a
combination of both.
- Arm II: Patients undergo surgery comprising breast-conserving therapy (BCT) or total
mastectomy according to patient and treating physician preference. Surgery is to occur
no later than 10 weeks after completion of 32 weeks of systemic therapy. Free surgical
margins must be achieved with re-excision or mastectomy for patients undergoing BCT.
After completion of BCT, patients undergo radiotherapy once a day, 5 days per week.
Patients who had mastectomy undergo radiotherapy at the discretion of treating
Patients may undergo blood and tumor tissue sample collection for circulating tumor cells
(CTC) burden and future studies.
Patients complete the Functional Assessment of Cancer Therapy - Breast Trial Outcome Index
(FACT- TOI) and FACT - General (22) and the Breast Cancer Subscale (FACT-B) quality-of-life
questionnaires at baseline and periodically during study.
After completion of study therapy, patients are followed up periodically for 5 years.
Combined Exercise Program for Early Breast Cancer Survivors
I. To determine whether a 16-week exercise intervention will improve components of
metastasis (MetS) in breast cancer survivors soon after completion of cancer-related
treatments by measuring changes in body composition, waist circumference, blood pressure,
and serum levels of insulin, glucose, lipids, C-reactive protein, and hemoglobin A1c
II. To determine whether a 16-week exercise intervention will improve physical fitness in
breast cancer survivors soon after completion of cancer-related treatments by measuring
cardiorespiratory fitness and muscle strength.
III. To assesses the feasibility of a supervised exercise intervention in early breast
IV. To determine whether a 16-week exercise intervention will result in a reduction in
adipose tissue inflammation in obese breast cancer survivors soon after completion of
cancer-related treatments by measuring ATM phenotype and ATM cytokine expression.
V. To determine whether breast cancer survivors can maintain positive benefits of an
exercise intervention following a 12-week follow-up period by measuring changes in body
composition, waist circumference, blood pressure, and serum levels of insulin, glucose,
lipids, C-reactive protein, and HbA1c, cardiorespiratory fitness and muscle strength.
Patients are randomized to 1 of 2 arms.
Arm I (Control): Patients refrain from increasing physical activity levels for 16 weeks.
Arm II (Exercise): Patients participate in supervised exercise sessions over 60 minutes
thrice weekly and are encouraged to participate in a home-based exercise session over 30-45
minutes once weekly for 16 weeks.
A Phase 2, Open-label, Multicenter, Safety and Efficacy Study of Oral Lucitanib in Patients With FGF Aberrant Metastatic Breast Cancer
Lucitanib is a selective, orally available tyrosine kinase inhibitor targeting FGFR1-3,
VEGFR1-3, and PDGFRα and β, with activity in relevant cell lines and animal models.
The first in human trial of lucitanib demonstrated that daily dosing with lucitanib can
provide durable clinical responses in patients with FGFR1- or 11q (FGF3, FGF4, Cyclin D1, or
FGF19)-amplified breast cancer. RECIST partial responses (PRs) were also observed in
patients not known to have FGF abnormalities.
Based on these results, is study is designed to explore the safety and anti-tumor activity
of daily lucitanib in breast cancer patients with and without alterations of the FGF
A Phase I/II Trial of Temsirolimus Plus Neratinib for Patients With Metastatic HER2-Amplified or Triple Negative Breast Cancer
Phase I Design
A standard, 3+3, dose escalation schedule will be used. Between 6 and 12 patients will
likely be necessary to determine the MTD of temsirolimus in combination with neratinib.
There will be no intrapatient dose escalation. The starting dose of temsirolimus is 8 mg
administered intravenously weekly (dose level 1). Three patients will initially be enrolled
in each cohort. The Phase I portion is closed to enrollment.
Phase II Design
The phase II portion of this trial will be comprised of two cohorts—HER2-amplified and
triple negative breast cancer—each of which has a Simon two-stage design to determine the
efficacy of temsirolimus when administered in combination with neratinib. Both pathologic
subtypes of patients will be studied separately though accrual will be simultaneous.
Response (RECIST criteria) will be assessed every 8 weeks (every 2 cycles) after the start
of therapy. As of 2/10/12, the Triple-negative cohort is closed to accrual. The HER2-
amplified cohort will continue to enroll as planned up to a total of 34 patients.
A Phase III, Randomized Clinical Trial of Standard Adjuvant Endocrine Therapy +/- Chemotherapy in Patients With 1-3 Positive Nodes, Hormone Receptor-Positive and HER2-Negative Breast Cancer With Recurrence Score (RS) of 25 or Less. RxPONDER: A Clinical Trial Rx for Positive Node, Endocrine Responsive Breast Cancer
I. To determine the effect of chemotherapy in patients with node positive breast cancer who
do not have high Recurrence Scores (RS) by Oncotype DX. In patients with 1-3 positive nodes,
and hormone receptor (HR)-positive, human epidermal growth factor receptor (HER)2-negative
breast cancer with RS =< 25 treated with endocrine therapy we will test whether the
difference in disease-free survival for patients treated with chemotherapy compared to no
chemotherapy depends directly on the magnitude of RS. If benefit depends on the RS score,
the trial will determine the optimal cutpoint for recommending chemotherapy or not.
I. To compare overall survival (OS), distant disease-free survival (DDFS), and local
disease-free interval (LDFI) by receipt of chemotherapy or not and its interaction with RS.
II. To compare the toxicity across the treatment arms. III. To perform other assays or tests
(in particular the PAM50 risk of relapse score) as they are developed and validated that
measure potential benefit of chemotherapy and compare them to Oncotype DX.
IV. To determine the impact of management with Oncotype DX on patient-reported anxiety
(co-primary Health-Related Quality of Life [HRQL] outcome) prior to screening, after
disclosure of test results, and during the randomized trial.
V. To determine the impact of Oncotype DX on the initial management cost of node-positive,
HR-positive, HER2-negative breast cancer.
VI. To compare patient-reported utilities (e.g., QOL) for those randomized to chemotherapy
versus no chemotherapy.
VII. To estimate the cost-effectiveness of management with Oncotype DX vs usual care using
modeling and DFS information from the trial.
VIII. To determine the role of other assays (e.g., PAM50) as predictors of DFS, DDFS, and
LDFI of patients randomized to chemotherapy versus no chemotherapy.
IX. To determine the impact of treatment with chemotherapy versus no chemotherapy on
patient-reported fatigue and cognitive concerns (secondary HRQL outcomes).
X. To determine the impact of management with Oncotype DX on patient-reported decision
conflict, perceptions regarding Oncotype DX testing, and survivor concerns prior to
screening, after disclosure of test results, and during the randomized trial (secondary HRQL
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive a protocol-approved chemotherapy regimen based on the patient and/or
physician preference. Patients then receive a protocol-approved adjuvant endocrine therapy
comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or
exemestane), or both for 5-10 years in the absence of disease progression or unacceptable
ARM II: Patients receive a protocol-approved endocrine therapy comprising tamoxifen citrate,
an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in
the absence of disease progression or unacceptable toxicity.
Patients may complete health-related quality-of-life (QOL) questionnaires at baseline and
periodically during study. Information on Medicare and/or insurance coverage and on health
coverage decisions may also be collected periodically.
After completion of study therapy, patients are followed up every 3 months for 2 years,
every 6 months for 3 years, and then yearly for at least 15 years.
Effect of Preoperative Breast MRI on Surgical Outcomes, Costs and Quality of Life of Women With Breast Cancer
This is a randomized trial of preoperative breast MRI in patients deemed eligible for breast
conserving surgery by conventional clinical criteria will provide important information
about the clinical and biologic relevance of occult disease identified by MRI alone.
Patients will be assigned to standard pre-operative breast cancer disease assessment without
the addition of MRI prior to breast conserving surgery or standard pre-operative breast
cancer disease assessment with the use of MRI prior to breast conserving surgery.
The primary objective is to compare the rates of local-regional recurrence (LRR) following
attempted breast conserving therapy in a cohort of women with triple negative or HER-2
amplified breast cancer randomized to preoperative staging with mammography (control arm) or
mammography plus breast MRI (MRI arm).
Secondary objectives are:
- To compare the re-operation rates following attempted breast conserving therapy between
women assessed preoperatively with breast MRI to those assessed without the use of
- To compare local recurrence rates between women who undergo BCT on the control arm to
women who undergo BCT on the MRI arm
- To compare the conversion rate to mastectomy secondary to persistent positive margins
or poor cosmesis within the first 6 months of attempting BCT (prior to the
administration of RT) between women assessed preoperatively with breast MRI to those
assessed without the use of breast MRI
- To compare the contralateral breast cancer rates in women randomized to preoperative
breast MRI to those not receiving pre-operative breast MRI
- To compare the disease-free survival rates between women assessed preoperatively with
breast MRI to those assessed without the use of breast MRI
- To compare breast cancer specific and overall survival outcomes of women assessed
preoperatively with breast MRI to those assessed without the use of breast MRI
- To estimate the rate of MRI-guided localization assisted surgery
- To estimate the rate of multi-centric disease in the index breast for women in the MRI
- To evaluate the accuracy of index lesion characteristics and other factors in
predicting multi-centricity in the cohort randomized to breast MRI
- To assess the positive predictive values (PPV) of MRI in detecting ipsilateral
multi-centric disease and contralateral disease in women with breast cancer undergoing
preoperative breast MRI
- To estimate the false positive rate for detection of multiple foci of breast cancer by
All registered patients will be monitored for relapse and survival for 5 years from the date
of surgery. Patients will be followed a minimum of every 4 months for the first 2 years from
diagnosis and a minimum of every 6 months during years 3-5. Patients will be monitored for
local, regional, distant relapse and vital status.
A Phase II-R and a Phase III Trial Evaluating Both *Erlotinib (PH II-R) and Chemoradiation (PH III) as Adjuvant Treatment For Patients With Resected Head of Pancreas Adenocarcinoma
I. To determine whether the addition of erlotinib (erlotinib hydrochloride) to gemcitabine
(gemcitabine hydrochloride) adjuvant chemotherapy shows a signal for improved survival as
compared to gemcitabine alone following R0 or R1 resection of head of pancreas
adenocarcinoma (including adenocarcinoma of the head, neck, and uncinate process). (Phase
II-R) II. To determine whether the use of concurrent fluoropyrimidine and radiotherapy
following adjuvant gemcitabine hydrochloride-based chemotherapy further enhances survival
for such patients who are without evidence of progressive disease after 5 cycles of
gemcitabine based chemotherapy. (Phase III)
I. To evaluate disease-free survival of adjuvant chemotherapy followed by radiotherapy and
concurrent fluoropyrimidine for patients with resected head of pancreas adenocarcinoma who
are disease free after 5 cycles of adjuvant chemotherapy.
II. To evaluate disease-free survival of standard adjuvant gemcitabine chemotherapy with and
without erlotinib for patients with resected head of pancreas adenocarcinoma.
III. To evaluate adverse events with and without erlotinib for patients with resected head
of pancreas adenocarcinoma.
IV. To evaluate adverse events of adjuvant chemotherapy with or without radiation therapy
and concurrent fluoropyrimidine for patients with resected head of pancreas adenocarcinoma
who are disease free after adjuvant chemotherapy.
V. To evaluate preoperative cross-sectional imaging of the primary head of pancreas
adenocarcinoma in order to determine the frequency with which objective criteria of
resectability are present.
VI. To determine if patients reporting low baseline fatigue, as measured by the Functional
Assessment of Chronic Illness Therapy (FACIT)-Fatigue, predicts survival and to explore
correlations between baseline fatigue, as measured by Patient-Reported Outcomes Measurement
Information System (PROMIS), and survival.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days
1, 8, and 15. Treatment repeats every 28 days for 5 courses in the absence of disease
progression or unacceptable toxicity.
ARM II: Patients receive gemcitabine hydrochloride as in arm I and erlotinib hydrochloride
orally (PO) once daily on days 1-28. Treatment repeats every 28 days for 5 courses in the
absence of disease progression or unacceptable toxicity. (NOTE: Phase II-R erlotinib
hydrochloride randomization completed, Arm 2 closed to accrual effective 2/19/2014)
Patients with no disease progression after treatment in arm I or II are then stratified
according to their first randomization treatment arm (arm I vs arm II) and randomized to 1
of 2 additional treatment arms (arm III or IV).
ARM III: Patients receive 1 course of the same treatment that they receive in arm I or II.
ARM IV: Patients receive 1 course of the same treatment that they receive in arm I or II.
Beginning within 7-21 days after completion of chemotherapy, patients undergo radiotherapy
(3-dimensional conformal radiotherapy or intensity-modulated radiotherapy) 5 days per week
for 5.5 weeks (28 fractions). During radiotherapy, patients receive either capecitabine PO
twice daily (BID) 5 days per week or fluorouracil IV continuously for 5.5 weeks or until
radiotherapy is completed.
After completion of study treatment, patients are followed up periodically.