Breast CancerPhase 2NCT00483223
Platinum for Triple-Negative Metastatic Breast Cancer and Evaluation of p63/p73 as a Biomarker of Response
A Phase 2 study testing Cisplatin and carboplatin in people with Breast Cancer, run by Massachusetts General Hospital at 10 sites in United States.
Trial summary
The purpose of this research study is to : Determine how effective cisplatin or carboplatin is in slowing the time it takes for ER negative (estrogen-receptor-negative), PR negative (progesterone receptor-negative), HER2 negative (human epidermal growth factor receptor 2) breast cancer to progress. 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 and carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 10 sitesUnited States
- Study dates
- Jun 2007to Jun 2017
- 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
- Histologically confirmed invasive breast cancer with stage IV disease, according to AJCC 6th edition (American Joint Committee on Cancer), either biopsy proven or with unequivocal evidence of metastatic disease by physical examination or radiological study
- All tumors must be ER-, PGR- and HER2-negative
- 18 years of age or older
- Paraffin tissue block is required from the primary tumor tissue or from diagnostic metastatic biopsy at time of relapse
- Measurable disease by RECIST
- Performance status of 0,1 or 2 by ECOG criteria (Eastern Cooperative Oncology Group)
- Life expectancy greater than 12 weeks
- Normal organ and bone marrow function documented within 14 days prior to enrollment as defined by the protocol
Who cannot join
- More than 1 prior chemotherapy for the treatment of recurrent or metastatic breast cancer
- Prior treatment with cisplatin, carboplatin, or other platinum chemotherapy agents
- Active brain metastases or unevaluated neurological symptoms suggestive of brain metastases
- Intercurrent illness or other major medical condition or comorbid condition that might affect study participation
- Significant history of uncontrolled cardiac disease such as uncontrolled hypertension, unstable angina, recent myocardial infarction, uncontrolled congestive heart failure, cardiomyopathy either symptomatic or asymptomatic but with decreased ejection fraction <45%
- Renal dysfunction for which cisplatin dose would either require dose modification or would be considered unsafe
- Pregnant or nursing women
- History or other malignancy that was not treated with curative intent
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Johns Hopkins University Medical Center
Baltimore, Maryland
University of Alabama-Birmingham
Birmingham, Alabama
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
University of North Carolina
Chapel Hill, North Carolina
Memorial Sloan Kettering Cancer Center
New York, New York
North Shore Medical Center
Peabody, Massachusetts, 01960
UCSF
San Francisco, California
Georgetown - Lombardi Cancer Center
Washington D.C., District of Columbia
About this study
Official title: A Phase II Study of Cisplatin or Carboplatin for Triple-Negative Metastatic Breast Cancer and Evaluation of p63/p73 as a Biomarker of Response
The purpose of this research study is to :
- Determine how effective cisplatin or carboplatin is in slowing the time it takes for ER negative (estrogen-receptor-negative), PR negative (progesterone receptor-negative), HER2 negative (human epidermal growth factor receptor 2) breast cancer to progress. Cisplatin and carboplatin are anti-cancer chemotherapy drugs that stop cancer cells from growing abnormally and is used to treat other cancers.
- Evaluate a new biomarker to help determine which breast cancers are most likely to respond to cisplatin chemotherapy
The hypothesis is that Triple Negative metastatic breast cancer may be particularly sensitive to platinum, and that a subgroup of those patients may have a marker in their tumors that predicts response.
Read the detailed description
This study is a Phase 2 study designed to evaluate cisplatin/carboplatin as first or second line therapy in metastatic triple negative (ER negative, PR negative, Her2 Negative) breast cancer and to evaluate the expression of p63/p73 as a biomarker to predict response.
- Participants will be given a cisplatin or carboplatin infusion intravenously on the first day of each treatment cycle. Each treatment cycle will last 3 weeks. Treating physician will select agent up to 41 patients in each cohort. Final primary endpoint analysis will use combined cis/carbo results.
- During all treatment cycles participants will have a physical exam (including weight and vital signs) and they will be asked general questions about their health and any medications they may be taking, as well as specific questions about any side effects they may be experiencing while receiving study treatment.
- During every treatment cycle participants will have standard blood tests to check blood counts, liver and kidney function, and a blood marker for you particular type of cancer.
- CT scans will be taken of the participants tumor every 2 to 3 cycles to assess the response of the tumor to cisplatin.
- Participants will be in this study for as long as they tolerate the study treatment and their disease does not get any worse.
- Participants will be required to have a sample of their original tumor sent to Massachusetts General Hospital for correlative studies, or a sample from a metastatic diagnostic biopsy.
- Patients with accessible tumor will be asked to provide an optional metastatic tumor biopsy for correlative studies.
- Conditions
- Breast Cancer
- Being tested
- Cisplatin, carboplatin
- Keywords
- ER negative, PgR negative, HER2 negative, cisplatin, carboplatinum, platinum, p63, p73
- Medical subject headings
- Breast Neoplasms, Ectrodactyly, Ectodermal Dysplasia, and Cleft Lip-Palate Syndrome 3
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CisplatinDrug
Also called Platinol
Given intravenously on the first day of each 3-week treatment cycle at 75mg/m2. Participants may continue to receive study treatment as long as their disease does not worsen and they do not experience serious side effects.
carboplatinDrug
Also called Paraplatin
Given intravenously on the first day of each 3-week treatment cycle at AUC 6. Participants may continue to receive study treatment as long as their disease does not worsen and they do not experience serious side effects.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Cisplatin or carboplatin (1 arm, 2 cohorts) Receives: Drug: Cisplatin; Drug: carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
Objective response rate (ORR) (complete response [CR]+ partial response [PR]) by RECIST (Response Evaluation Criteria In Solid Tumors).
Complete Response (CR): Disappearance of all target lesions
Partial Response (PR): At least a 30% decrease in the sum of the LD (longest diameter) of target lesions, taking as reference the baseline sum LD
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Measured: 3 years
Response Rate Categorized by p63/p73 Ratio
Response rate categorized by pre-specified ΔNp63/TAp73 expression ratio cutoff in the primary tumors from this patient cohort as a bio-marker to predict response to cisplatin or carboplatin. Response is defined as partial or completed response as determined by RECIST. Expression ratio was measured using quantitative RT-PCR (Reverse transcription polymerase chain reaction).
Measured: 3 years
Secondary outcomes (2)
Objective Response Rate Categorized by Subgroup
The number of participants achieving an objective response (as determined by RECIST) categorized by treatment cohort and whether the treatment was first or second line treatment. First line treatment means that the drug used was the first drug used for the treatment of the primary cancer. Second line treatment means that a first line treatment failed to produce the desired response, so a new drug was used for treatment.
Measured: 3 years
Progression Free Survival and Overall Survival
Median progression free survival and overall survival (progression determined using RECIST) during a median follow-up time of 50 months.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2007 (estimated)
- Study startJun 2007
- Primary completionJun 2014
- Study completionJun 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute, North Shore Medical Center
- Responsible party
- Principal investigator, Steven Isakoff, MD, PhD, Massachusetts General Hospital
- Investigators
- Steven Isakoff, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00483223
- Sponsor's protocol ID
- 06-412
- Other IDs
- TBCRC009
- Status last verified
- Jul 2017
- First submitted
- 5 Jun 2007
- Last updated
- 25 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Isakoff SJ, Mayer EL, He L, Traina TA, Carey LA, Krag KJ, Rugo HS, Liu MC, Stearns V, Come SE, Timms KM, Hartman AR, Borger DR, Finkelstein DM, Garber JE, Ryan PD, Winer EP, Goss PE, Ellisen LW. TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With Biomarker Assessment in Metastatic Triple-Negative Breast Cancer. J Clin Oncol. 2015 Jun 10;33(17):1902-9. doi: 10.1200/JCO.2014.57.6660. Epub 2015 Apr 6.
PubMed 25847936
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Cisplatin or Carboplatin for Triple-Negative Metastatic Breast Cancer and Evaluation of p63/p73 as a Biomarker of Response
- ClinicalTrials.gov ID
- NCT00483223
- Acronym / sponsor ID
- 06-412
- Conditions
- Breast Cancer
- Keywords
- ER negative, PgR negative, HER2 negative, cisplatin, carboplatinum, platinum, p63, p73
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute, North Shore Medical Center
- Study start
- Jun 2007
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 6 Jun 2007 (estimated)
- Results
- Posted 1 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to :
- Determine how effective cisplatin or carboplatin is in slowing the time it takes for ER negative (estrogen-receptor-negative), PR negative (progesterone receptor-negative), HER2 negative (human epidermal growth factor receptor 2) breast cancer to progress. Cisplatin and carboplatin are anti-cancer chemotherapy drugs that stop cancer cells from growing abnormally and is used to treat other cancers.
- Evaluate a new biomarker to help determine which breast cancers are most likely to respond to cisplatin chemotherapy
The hypothesis is that Triple Negative metastatic breast cancer may be particularly sensitive to platinum, and that a subgroup of those patients may have a marker in their tumors that predicts response.
Detailed description
This study is a Phase 2 study designed to evaluate cisplatin/carboplatin as first or second line therapy in metastatic triple negative (ER negative, PR negative, Her2 Negative) breast cancer and to evaluate the expression of p63/p73 as a biomarker to predict response.
- Participants will be given a cisplatin or carboplatin infusion intravenously on the first day of each treatment cycle. Each treatment cycle will last 3 weeks. Treating physician will select agent up to 41 patients in each cohort. Final primary endpoint analysis will use combined cis/carbo results.
- During all treatment cycles participants will have a physical exam (including weight and vital signs) and they will be asked general questions about their health and any medications they may be taking, as well as specific questions about any side effects they may be experiencing while receiving study treatment.
- During every treatment cycle participants will have standard blood tests to check blood counts, liver and kidney function, and a blood marker for you particular type of cancer.
- CT scans will be taken of the participants tumor every 2 to 3 cycles to assess the response of the tumor to cisplatin.
- Participants will be in this study for as long as they tolerate the study treatment and their disease does not get any worse.
- Participants will be required to have a sample of their original tumor sent to Massachusetts General Hospital for correlative studies, or a sample from a metastatic diagnostic biopsy.
- Patients with accessible tumor will be asked to provide an optional metastatic tumor biopsy for correlative studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: Cisplatin, Drug: carboplatinCisplatin or carboplatin (1 arm, 2 cohorts) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically confirmed invasive breast cancer with stage IV disease, according to AJCC 6th edition (American Joint Committee on Cancer), either biopsy proven or with unequivocal evidence of metastatic disease by physical examination or radiological study
- All tumors must be ER-, PGR- and HER2-negative
- 18 years of age or older
- Paraffin tissue block is required from the primary tumor tissue or from diagnostic metastatic biopsy at time of relapse
- Measurable disease by RECIST
Key exclusion criteria (8 listed)
- More than 1 prior chemotherapy for the treatment of recurrent or metastatic breast cancer
- Prior treatment with cisplatin, carboplatin, or other platinum chemotherapy agents
- Active brain metastases or unevaluated neurological symptoms suggestive of brain metastases
- Intercurrent illness or other major medical condition or comorbid condition that might affect study participation
- Significant history of uncontrolled cardiac disease such as uncontrolled hypertension, unstable angina, recent myocardial infarction, uncontrolled congestive heart failure, cardiomyopathy either symptomatic or asymptomatic but with decreased ejection fraction <45%
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 |
|---|---|---|
| CisplatinAlso: PlatinolGiven intravenously on the first day of each 3-week treatment cycle at 75mg/m2. Participants may continue to receive study treatment as long as their disease does not worsen and they do not experience serious side effects. | Drug | Single Arm |
| carboplatinAlso: ParaplatinGiven intravenously on the first day of each 3-week treatment cycle at AUC 6. Participants may continue to receive study treatment as long as their disease does not worsen and they do not experience serious side effects. | Drug | Single Arm |
Primary outcome
Objective Response Rate
Time frame: 3 years
Objective response rate (ORR) (complete response [CR]+ partial response [PR]) by RECIST (Response Evaluation Criteria In Solid Tumors). Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD (longest diameter) of target lesions, taking as reference the baseline sum LD Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Response Rate Categorized by p63/p73 Ratio
Time frame: 3 years
Response rate categorized by pre-specified ΔNp63/TAp73 expression ratio cutoff in the primary tumors from this patient cohort as a bio-marker to predict response to cisplatin or carboplatin. Response is defined as partial or completed response as determined by RECIST. Expression ratio was measured using quantitative RT-PCR (Reverse transcription polymerase chain reaction).
2 secondary outcomes
Objective Response Rate Categorized by Subgroup
Time frame: 3 years
Progression Free Survival and Overall Survival
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25847936Isakoff SJ, Mayer EL, He L, Traina TA, Carey LA, Krag KJ, Rugo HS, Liu MC, Stearns V, Come SE, Timms KM, Hartman AR, Borger DR, Finkelstein DM, Garber JE, Ryan PD, Winer EP, Goss PE, Ellisen LW. TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With Biomarker Assessment in Metastatic Triple-Negative Breast Cancer. J Clin Oncol. 2015 Jun 10;33(17):1902-9. doi: 10.1200/JCO.2014.57.6660. Epub 2015 Apr 6.
- Individual participant dataSharing planned: No
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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.
Steven Isakoff, MD, PhD principal investigator
Massachusetts General Hospital
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cisplatin and carboplatin in people with Breast Cancer, run by Massachusetts General Hospital at 10 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 8 inclusion and 8 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 25 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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 1 Jun 2017). 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?
Objective Response Rate (time frame: 3 years). The study lists 2 primary outcomes in all. 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 NCT00483223, 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 25 Aug 2017.