Breast CancerPhase 1/2NCT01031446
Cisplatin, Paclitaxel, and Everolimus in Treating Patients With Metastatic Breast Cancer
A Phase 1/2 study testing cisplatin, everolimus and paclitaxel in people with Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 4 sites in United States.
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
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 4 sitesUnited States
- Study dates
- Oct 2009to Aug 2017
- Phase
- Phase 1/2
- 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
DISEASE CHARACTERISTICS:
- Histologically confirmed invasive mammary carcinoma
- Stage IV disease
- Basal-like disease (triple-negative, hormone-refractory, HER2-negative)
- No locally recurrent breast cancer
- No symptomatic brain metastases
- Patients with a history of brain metastases are eligible provided they are clinically stable for > 3 weeks after completion of radiotherapy and are not taking steroids or therapeutic anticonvulsants that are cytochrome P450 3A4 (CYP3A4) modifiers
- Patients with asymptomatic brain metastases are eligible provided they are not taking prophylactic anticonvulsants that are CYP3A4 modifiers
PATIENT CHARACTERISTICS:
- Pre- or post-menopausal
- European Cooperative Oncology Group (ECOG) performance status 0-1
- Life expectancy ≥ 6 months
- Absolute neutrophil count (ANC) ≥ 1,000/mm^3
- Platelet count ≥ 100,000/mm^3
- Creatinine ≤ 1.5 times upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 times ULN (≤ 3 times ULN in the presence of liver metastasis)
- Direct bilirubin will be measured in patients with Gilbert syndrome
- serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) ≤ 1.5 times ULN (≤ 3 times ULN in the presence of liver metastasis)
- Alkaline phosphatase ≤ 3 times ULN (in the presence of liver metastasis)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception during and for 3 months after completion of study treatment
- Able to swallow and retain oral medication
- No malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel
- No concurrent uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection requiring parenteral antibiotics
- Impaired lung function (chronic obstructive pulmonary disease or lung conditions requiring oxygen therapy)
- New York Heart Association class III-IV congestive heart failure
- Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within the past 6 months
- Uncontrolled hypertension (systolic BP > 180 mm Hg or diastolic BP > 100 mm Hg, found on 2 consecutive measurements separated by a 1-week period and despite adequate medical support)
- Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment [grade 3 according to NCI Common Toxicity Criteria for Adverse Events v3.0])
- Uncontrolled diabetes (hyperosmolar state, ketoacidosis, etc.)
- Psychiatric illness or social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary
- No symptomatic neuropathy ≥ grade 2
- No other invasive cancer within the past 5 years except for completely resected basal cell or squamous cell carcinoma of the skin or successfully treated cervical carcinoma in situ
- No hypersensitivity to paclitaxel or drugs using the vehicle Cremophor, Chinese hamster ovary cell products, or other recombinant human antibodies
- No history of hepatitis B or C
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from prior therapy
- Prior total cumulative life-time dose of doxorubicin ≤ 360 mg/m^2 or epirubicin ≤ 640 mg/m^2
- No more than 4 prior chemotherapy treatments in the metastatic setting (not including endocrine therapy or single-agent biologic therapy)
- At least 2 weeks since prior investigational drugs
- At least 14 days since prior and no concurrent herbal or dietary supplements
- At least 14 days since prior and no concurrent CYP3A4 inducers
- At least 7 days since prior and no concurrent CYP3A4 inhibitors
- Concurrent radiotherapy to painful bone metastases or areas of impending bone fracture allowed provided radiotherapy is initiated before study entry
- No other concurrent anticancer therapy (chemotherapy, radiotherapy, surgery, immunotherapy, hormonal therapy, biologic therapy)
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Erlanger Cancer Center at Erlanger Hospital - Baroness
Chattanooga, Tennessee, 37403
West Tennessee Cancer Center at Jackson-Madison County General Hospital
Jackson, Tennessee, 38301
Baptist Regional Cancer Center at Baptist Riverside
Knoxville, Tennessee, 37901
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838
About this study
Official title: A Phase Ib/II Study of Cisplatin, Paclitaxel, and RAD001 in Patients With Metastatic 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 cisplatin and paclitaxel together with everolimus may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects of giving cisplatin and paclitaxel together with everolimus and to see how well it works in treating patients with metastatic breast cancer.
Read the detailed description
OBJECTIVES:
Primary
- Safety profile of cisplatin, paclitaxel, and everolimus (RAD001) in patients with metastatic breast cancer. (Phase I)
- Progression-free survival (Phase II)
Secondary
- Overall response rate
- Time to progression
- Number of patients with worst-grade toxicities Tertiary
- To determine p53, p63, p73, and phosphatase and tensin homolog (PTEN) levels by immunohistochemistry (IHC).
- To screen for exon 9 (E542K and E545K), exon 20 (H1047R), and phosphatidylinositol 3-kinase (PI3K) (p110α) mutations in DNA extracted from paraffin blocks.
- To correlate IHC results with clinical outcome and with the different subtypes of breast cancer determined by molecular classification (basal-type vs luminal A vs luminal B) based on microarrays of RNA extracted from formalin-fixed paraffin-embedded blocks.
- To generate microarrays of RNA extracted from fresh-frozen core biopsies (when available) to identify a pretreatment gene signature that mirrors the established p63 and p73 gene signatures that predict response to treatment.
OUTLINE: This is a multicenter study.
Patients receive oral everolimus once daily on days 1-28 and cisplatin IV over 1 hour and paclitaxel IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Tumor tissue samples are collected at baseline for correlative studies.
After completion of study treatment, patients are followed up at 4 weeks.
- Conditions
- Breast Cancer
- Being tested
- cisplatin, everolimus, paclitaxel, laboratory biomarker analysis
- Keywords
- stage IV breast cancer, Human epidermal growth factor (HER2)-negative breast cancer, triple-negative breast cancer, hormone-resistant breast cancer
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cisplatinDrug
Given through a vein in the arm 1 time a week for 3 weeks, then a one week break and then begin the process again.
everolimusDrug
Taken daily by mouth.
paclitaxelDrug
Given through a vein in the arm 1 time a week for 3 weeks, then a one week break and then begin the process again.
laboratory biomarker analysisOther
Blood collection
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Not described Receives: Drug: cisplatin; Drug: everolimus; Drug: paclitaxel; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Feasible Dose in Milligrams Per Meter Squared of Body Surface Area (mg/m2) of Cisplatin and Paclitaxel for Women With Metastatic Breast Cancer
The recommended dose for the Phase II trial will be the most prevalent dose delivered per week in Phase I that allows for safe and feasible administration of the medications.The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 x 10 9/L for > 5 days), febrile neutropenia (ANC < 1.0 x 10 0/L with fever > 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia < 25 x 10 9/L or CTC Grade 3 < 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy.
Measured: at 8 weeks
Maximum Feasible Dose in mg of RAD001 (Everolimus)for Women With Metastatic Breast Cancer
The recommended dose for the Phase II trial will be the most prevalent dose delivered per day in Phase I that allows for safe and feasible administration the medication. The MTD is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 x 10 9/L for > 5 days), febrile neutropenia (ANC < 1.0 x 10 0/L with fever > 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia < 25 x 10 9/L or CTC Grade 3 < 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy
Measured: at 8 weeks
Patients With Progression-free Survival
Patients who had not experienced disease progression and who were alive at 6 months after study entry
Measured: at 6 months
Secondary outcomes (3)
Patients With Overall Response
Per Response Evaluation Criteria in Solid Tumor (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: every 12 weeks
Time to Progression
Duration in months from date on-study to date patient exhibited progressive disease
Measured: Up to 64 weeks
Time to Progression in Patients With Metastatic Basal-like Breast Cancer.
Median duration in months from on-study to disease progression in patients with metastatic basal-like breast cancer. All patients with basal-like breast cancer are negative for estrogen, progesterone, and human epidermal growth factor (HER2) receptors.
Measured: Up to 64 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2009 (estimated)
- Study startOct 2009
- Primary completionDec 2011
- Study completionAug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Ingrid Mayer, MD, Vanderbilt-Ingram Cancer Center
- Investigators
- Ingrid Mayer, MD, Principal investigator, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01031446
- Sponsor's protocol ID
- VICC BRE 0949
- Other IDs
- P30CA068485, VU-VICC-BRE-0949, IRB# 090673
- Status last verified
- Aug 2018
- First submitted
- 11 Dec 2009
- Last updated
- 31 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study of Cisplatin, Paclitaxel, and RAD001 in Patients With Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT01031446
- Acronym / sponsor ID
- VICC BRE 0949
- Conditions
- Breast Cancer
- Keywords
- stage IV breast cancer, Human epidermal growth factor (HER2)-negative breast cancer, triple-negative breast cancer, hormone-resistant breast cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Oct 2009
- Primary completion
- Dec 2011 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 14 Dec 2009 (estimated)
- Results
- Posted 11 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 cisplatin and paclitaxel together with everolimus may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects of giving cisplatin and paclitaxel together with everolimus and to see how well it works in treating patients with metastatic breast cancer.
Detailed description
OBJECTIVES:
Primary
- Safety profile of cisplatin, paclitaxel, and everolimus (RAD001) in patients with metastatic breast cancer. (Phase I)
- Progression-free survival (Phase II)
Secondary
- Overall response rate
- Time to progression
- Number of patients with worst-grade toxicities Tertiary
- To determine p53, p63, p73, and phosphatase and tensin homolog (PTEN) levels by immunohistochemistry (IHC).
- To screen for exon 9 (E542K and E545K), exon 20 (H1047R), and phosphatidylinositol 3-kinase (PI3K) (p110α) mutations in DNA extracted from paraffin blocks.
- To correlate IHC results with clinical outcome and with the different subtypes of breast cancer determined by molecular classification (basal-type vs luminal A vs luminal B) based on microarrays of RNA extracted from formalin-fixed paraffin-embedded blocks.
- To generate microarrays of RNA extracted from fresh-frozen core biopsies (when available) to identify a pretreatment gene signature that mirrors the established p63 and p73 gene signatures that predict response to treatment.
OUTLINE: This is a multicenter study.
Patients receive oral everolimus once daily on days 1-28 and cisplatin IV over 1 hour and paclitaxel IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Tumor tissue samples are collected at baseline for correlative studies.
After completion of study treatment, patients are followed up at 4 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: cisplatin, Drug: everolimus, Drug: paclitaxel, Other: laboratory biomarker analysis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cisplatinGiven through a vein in the arm 1 time a week for 3 weeks, then a one week break and then begin the process again. | Drug | Treatment |
| everolimusTaken daily by mouth. | Drug | Treatment |
| paclitaxelGiven through a vein in the arm 1 time a week for 3 weeks, then a one week break and then begin the process again. | Drug | Treatment |
| laboratory biomarker analysisBlood collection | Other | Treatment |
Primary outcome
Maximum Feasible Dose in Milligrams Per Meter Squared of Body Surface Area (mg/m2) of Cisplatin and Paclitaxel for Women With Metastatic Breast Cancer
Time frame: at 8 weeks
The recommended dose for the Phase II trial will be the most prevalent dose delivered per week in Phase I that allows for safe and feasible administration of the medications.The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 x 10 9/L for > 5 days), febrile neutropenia (ANC < 1.0 x 10 0/L with fever > 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia < 25 x 10 9/L or CTC Grade 3 < 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy.
Maximum Feasible Dose in mg of RAD001 (Everolimus)for Women With Metastatic Breast Cancer
Time frame: at 8 weeks
The recommended dose for the Phase II trial will be the most prevalent dose delivered per day in Phase I that allows for safe and feasible administration the medication. The MTD is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 x 10 9/L for > 5 days), febrile neutropenia (ANC < 1.0 x 10 0/L with fever > 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia < 25 x 10 9/L or CTC Grade 3 < 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy
Patients With Progression-free Survival
Time frame: at 6 months
Patients who had not experienced disease progression and who were alive at 6 months after study entry
3 secondary outcomes
Patients With Overall Response
Time frame: every 12 weeks
Time to Progression
Time frame: Up to 64 weeks
Time to Progression in Patients With Metastatic Basal-like Breast Cancer.
Time frame: Up to 64 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ingrid Mayer, MD principal investigator
Vanderbilt-Ingram Cancer Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing cisplatin, everolimus and paclitaxel in people with Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 4 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?
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 31 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 11 Mar 2013). 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?
Maximum Feasible Dose in Milligrams Per Meter Squared of Body Surface Area (mg/m2) of Cisplatin and Paclitaxel for Women With Metastatic Breast Cancer (time frame: at 8 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Aug 2018.