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Breast CancerPhase 2NCT00930930

Cisplatin and Paclitaxel With or Without Everolimus in Treating Patients With Stage II or Stage III Breast Cancer

A Phase 2 study testing cisplatin, everolimus and paclitaxel in people with Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
cisplatin, everolimus and paclitaxel
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
145 participants
Where
8 sitesUnited States
Study dates
Jun 2009to Oct 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must provide informed written consent.
  • Patient must be ≥ 18 years of age.
  • ECOG performance status 0-1.
  • Clinical stage II or stage III triple-negative (ER and/or PR no staining or weak staining in less than or equal to 10% cells by immunohistochemistry [IHC] and HER2-negative by Herceptest [0, 1+] or FISH) invasive mammary carcinoma, confirmed by histological analysis.
  • Patients who have measurable* residual tumor at the primary site
  • Measurable disease: any mass that can be reproducibly measured by physical examination, mammogram, and/or ultrasound and can be accurately measured in at least one dimension (longest diameter to be recorded) as 10 mm (1 cm), either in the breast or axillary lymph nodes.
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  • Available core biopsies from the time of diagnosis. Fresh tissue must be obtainable at baseline or fresh tissue biopsy prior to treatment initiation.
  • Patients who will undergo surgical treatment with either segmental resection or total mastectomy.
  • Patients must have adequate hematologic, hepatic, and renal function. All tests must be obtained less than 4 weeks from study entry. This includes:
  • ANC >/=1500/mm3
  • Platelet count >/=100,000/mm3
  • Creatinine </=1.5X upper limits of normal
  • Bilirubin, SGOT, SGPT </=1.5X upper limits of normal*
  • for patients with Gilbert"s syndrome, direct bilirubin will be measured instead of total bilirubin.
  • The patient must have not had anyprior chemotherapy for primary breast cancer.
  • Patients with a prior history of contra-lateral breast cancer are eligible if they have no evidence of recurrence of their initial primary breast cancer within the last 5 years.
  • Able to swallow and retain oral medication.
  • Four days prior to biopsy procedures patients must be off medications that could increase risk of bleeding (i.e. ASA, NSAIDS, Coumadin, heparin products)
  • Potential subjects must complete all screening assessments as outlined in the protocol.
  • The pre-menopausal patient of childbearing potential must have had a negative pregnancy test and agreed to use birth control methods while participating in the study. Note: Women of childbearing potential and their male counterparts should use a barrier method of contraception during and for 3 months following protocol therapy.
  • Ineligibility Criteria

Who cannot join

  • Locally recurrent breast cancer.
  • Pregnant or lactating women.
  • Evidence of distant metastatic disease (i.e. lung, liver, bone, brain, etc.)
  • Use of CYP3A4 modifiers (Appendix A)
  • Serious medical illness that in the judgment of the treating physician places the patient at high risk of operative mortality.
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
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  • History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinomas are eligible.
  • History of hepatitis B or hepatitis C. If patient is judged to be at risk for having had exposure to viral B or C hepatitis (i.e. illicit IV drug use, blood transfusion prior to 1990, body piercing, tattoos, etc.), appropriate testing should be performed (i.e. Hepatitis B surface antigen antibody, and Hepatitis C antibody)
  • Active or uncontrolled infection requiring parenteral antibiotics.
  • Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  • Symptomatic neuropathy (≥ grade 2).
  • Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, or any other biologic therapy) other than the ones specified in the protocol.
  • Concurrent treatment with an investigational agent.
  • Used an investigational drug within 15 days or 5 half-lives, whichever is longer, preceding the first dose of randomized therapy.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites
  • University of Alabama

    Birmingham, Alabama, 35249

  • University of Virginia Health Sciences Center

    Charlottesville, Virginia, 22098

  • Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • The Methodist Hospital Research Institute

    Houston, Texas, 77030

  • University of Mississippi Medical Center Research Institute

    Jackson, Mississippi, 39213

  • Vanderbilt-Ingram Cancer Center - Cool Springs

    Nashville, Tennessee, 37064

  • MBCCOP - Meharry Medical College - Nashville

    Nashville, Tennessee, 37208

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232-6838

Other trials in United States

About this study

Official title: A Phase II Neo-Adjuvant Study of Cisplatin, Paclitaxel With or Without RAD001 in Patients With Triple-negative Locally Advanced Breast Cancer.

RATIONALE: Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving chemotherapy together with everolimus before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether cisplatin and paclitaxel are more effective when given together with or without everolimus in treating patients with breast cancer.

PURPOSE: This randomized phase II trial is studying how well cisplatin and paclitaxel work when given together with or without everolimus in treating patients with stage II or stage III breast cancer.

Read the detailed description

OBJECTIVES:

Primary

  • To determine the pathological complete response in patients with triple-negative, stage II or III breast cancer treated with neoadjuvant cisplatin and paclitaxel with or without everolimus.

Secondary

  • To determine the safety profile of these treatment regimens.
  • To evaluate tumor response to these treatment regimens as measured by ultrasound before definitive surgery.
  • To evaluate the rate of breast conservation surgery after treatment with these regimens.
  • To determine treatment-mediated changes in cell cycle position, proliferation, and apoptosis as well as status, levels, and phosphorylation state of S6K, p53, p73, and p63 and select p53 family target genes before and after initiation of paclitaxel.
  • To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to identify a pre-treatment gene signature that will predict response.
  • To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to identify a change in gene signature after the first treatment that will predict response.
  • To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to determine if previously established p63 and p73 gene signatures predict response to treatment.
  • To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to determine if a change will be observed in p63 and p73 gene signatures between pre- and post-treatment biopsies.
  • To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to determine if triple-negative breast cancers can be clustered into different subtypes on the basis of gene expression, given the size of the microarray data set that will be generated from this clinical trial and previous clinical trials (> 100 tumors).
  • To isolate RNA and generate microarray data sets from pre- and post-treatment biopsy material to determine if p63 and p73 gene signatures can sub-classify triple-negative breast cancers.

OUTLINE: This is a multicenter study. Patients are stratified according to initial lymph node status (positive vs negative involvement) and tumor grade (low or intermediate vs high). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive cisplatin IV over 1 hour and oral everolimus once weekly in weeks 1-12 and paclitaxel IV over 1 hour once weekly in weeks 4-12 in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive cisplatin IV over 1 hour and oral placebo once weekly in weeks 1-12 and paclitaxel IV over 1 hour once weekly in weeks 4-12 in the absence of disease progression or unacceptable toxicity.

Approximately 3-6 weeks after the completion of neoadjuvant therapy, patients undergo partial or total mastectomy with lymph node evaluation. Patients may then receive additional chemotherapy or radiotherapy.

Patients undergo ultrasound-guided core biopsies at baseline and in weeks 1, 4, and 12 for analysis of proliferation, apoptosis, and pathway activity markers via IHC or western blotting and RNA microarrays.

Patients are followed up within 3 weeks after surgery.

Conditions
Breast Cancer
Being tested
cisplatin, everolimus, paclitaxel, placebo, Venous blood draw
Keywords
triple-negative breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, male breast cancer
Medical subject headings
Breast Neoplasms, Triple Negative Breast Neoplasms, Breast Neoplasms, Male

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cisplatinDrug

    Given IV

  • everolimusDrug

    Given orally

  • paclitaxelDrug

    Given IV

  • placeboOther

    Given orally

  • Venous blood drawProcedure or surgery

    Venous blood (2-3 tablespoons) will be taken for germline DNA analysis to complement the correlative studies in the tumor tissue. Blood can be drawn at any time prior, during, or after completion of study treatment

Study groups in NCT00930930
Study groupRoleWhat they receive
Cisplatin and Paclitaxel + RAD001ExperimentalCisplatin 25 mg/m2 IV weekly + RAD001 5 mg PO daily for 1 week followed by Cisplatin 25 mg/m2 IV + Paclitaxel 80 mg/m2 IV weekly + RAD001 5 mg PO daily for 11 weeks
Receives: Drug: cisplatin; Drug: everolimus; Drug: paclitaxel; Procedure: Venous blood draw
Cisplatin and Paclitaxel + PlaceboActive comparatorCisplatin 25 mg/m2 IV weekly + placebo PO daily for 1 week followed by Cisplatin 25 mg/m2 IV + Paclitaxel 80 mg/m2 IV weekly + placebo PO daily for 11 weeks
Receives: Drug: cisplatin; Drug: paclitaxel; Other: placebo; Procedure: Venous blood draw

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients With Pathological Complete Response

    Pathological complete response is defined as no residual tumor on histopathological analysis of both breast and axillary contents.

    Measured: at time of surgery, week 15-18

Secondary outcomes (3)
  1. Number of Patients That Underwent Breast Conservation Surgery

    Defined as patients that did not undergo complete removal of a cancerous breast (mastectomy).

    Measured: at the time of surgery, week 15-18

  2. Clinical Tumor Response to Neoadjuvant Therapy as Measured by Ultrasound Immediately Before Surgery

    Per RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions

    Measured: After treatment, week 12-15

  3. Number of Patients With Each Worst-grade Toxicity Response

    Tables represent the number of patients with their worst-grade toxicity at each of five grades (grade 1, least severe to grade 5, most severe) following NCI Common Toxicity Criteria. Not all participants necessarily have an adverse event, thus not everyone will be accounted for in worst-grade toxicities. Likewise, one participant can potentially have more than one event in various grades 1-5 which accounts for the difference in number of patients analyzed and total number in the worst-grade toxicity tables.

    Measured: week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2009 (estimated)
  2. Study startJun 2009
  3. Primary completionOct 2013
  4. Study completionOct 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
145 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00930930
Sponsor's protocol ID
VICC BRE 0904
Other IDs
P30CA068485, VU-VICC-BRE-0904, IRB# 090291
Status last verified
May 2015
First submitted
1 Jul 2009
Last updated
7 May 2015
Data monitoring committee
Yes

Publications

  • Jovanovic B, Sheng Q, Seitz RS, Lawrence KD, Morris SW, Thomas LR, Hout DR, Schweitzer BL, Guo Y, Pietenpol JA, Lehmann BD. Comparison of triple-negative breast cancer molecular subtyping using RNA from matched fresh-frozen versus formalin-fixed paraffin-embedded tissue. BMC Cancer. 2017 Apr 4;17(1):241. doi: 10.1186/s12885-017-3237-1.

    PubMed 28376728

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cisplatin, everolimus and paclitaxel in people with Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Pathological Complete Response (time frame: at time of surgery, week 15-18). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00930930, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2015.

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