HER2 Positive Untreated Metastatic Breast CancerPhase 1NCT02598427
Intrathecal Pertuzumab and Trastuzumab in Patients With New Untreated Asymptomatic or Low Symptomatic Brain Metastasis in HER2 Positive Breast Cancer
A Phase 1 study testing Pertuzumab and Trastuzumab in people with HER2 Positive Untreated Metastatic Breast Cancer and Asymptomatic or Low Symptomatic Brain Metastasis in Breast Cancer, run by Kimberly Blackwell at 1 site in United States.
Trial summary
The purpose of this research study is to determine how well pertuzumab and trastuzumab works in treating breast cancer that has spread to the brain. Pertuzumab and trastuzumab are treatments that stop breast cancer cells from growing abnormally by inhibiting (or blocking) members of a family of proteins that include… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2 Positive Untreated Metastatic Breast Cancer, Asymptomatic or Low Symptomatic Brain Metastasis in Breast Cancer
- What is being tested?
- Pertuzumab and Trastuzumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2017to 22 Feb 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- HER2 positive by 2013 ASCO-CAP guidelines (IHC 3+ and/or FISH positive; IHC 2+ HER2 patients are eligible with reflex FISH positive testing with the ratio ≥ 2.0) breast cancer patients with untreated asymptomatic or minimally symptomatic brain metastasis by MRI. There is no upper or lower limit to the size or number of brain metastases.
- Patients can have previous brain metastasis that was completely surgically resected if the previously resected lesion is at least 1 cm from target lesion(s) for this study. The location of the previous resection cavity is determined by the post-resection MRI.
- Patients can have previous brain metastasis that was treated with stereotactic radiosurgery (SRS) if the previously treated lesion is at least 1cm from the target lesion(s) for this study. The location of the previous SRS treatment location is determined by the SRS MRI.
- Patients can be on steroids as long as the dose has been stable for ≥ 7 days
- No limitations on prior systemic or intrathecal therapies.
- There are no restrictions on systemic therapy at enrollment.
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- Negative serum pregnancy test for pre-menopausal women and women within 12 months from the onset of menopause.
- Sexually active women of childbearing potential must commit to 2 methods of contraception while enrolled on the trial and continue using contraceptives for at least 7 months post study drug administration. Sexually active men must commit to 1 method of contraception while enrolled and for 7 months after. Hormonal contraceptives such as birth control pills, patches, implants or injections are not allowed in patients who are HR+.
- Life expectancy ≥ 8 weeks
- Laboratory criteria: normal renal function: creatinine < 1.5 x upper limit of normal (ULN)), liver function: bilirubin ≤ 1.5 x ULN, transaminases ≤ 2 x ULN, except in known hepatic disease, wherein may be ≤ 5 x ULN, and blood counts: WBC ≥ 2.0, Neutrophils ≥1500, platelets ≥100,000, Hemoglobin ≥ 10.
- LVEF (left ventricular ejection fraction) ≥ 50%
- Karnofsky performance status (KPS) ≥ 50
- Age ≥ 18 years
- Patients must have the ability to give informed consent.
- Patients must sign an informed consent form.
Who cannot join
- No seizures, focal weakness of any extremity (by neurologic exam), or stroke symptoms in the past month.
- No history of prior whole brain radiation.
- No history of lumbar surgery or other pre-existing spinal conditions that would preclude frequent, safe, reliable lumbar punctures.
- No history of serious cardiac arrhythmia or EF < 50%.
- Systemic sites of disease need to be stable on systemic therapy based on the most recent (within 12 weeks) staging scans.
- Radiation while on study is not allowed EXCEPT to a localized region for pain control.
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- No history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) unless the patient has been in remission and off all other cancer therapy for at least 3 years.
- Patients should have no significant psychiatric illness or medical illness that would preclude the ability to comply with the protocol.
- Patients may not be pregnant or breastfeeding.
- No known hypersensitivity to trastuzumab or pertuzumab.
- Symptomatic intrinsic lung disease or extensive tumor involvement in the lungs resulting in dyspnea at rest.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: Phase I Dose Escalation Trial of Intrathecal Pertuzumab and Trastuzumab in Patients With New Untreated Asymptomatic or Low Symptomatic Brain Metastasis
The purpose of this research study is to determine how well pertuzumab and trastuzumab works in treating breast cancer that has spread to the brain. Pertuzumab and trastuzumab are treatments that stop breast cancer cells from growing abnormally by inhibiting (or blocking) members of a family of proteins that include Human Epidermal Growth Factor Receptor 2 (HER2).
Pertuzumab and trastuzumab have been found to be very effective for HER2-positive breast cancer and are FDA approved for treatment of metastatic breast cancer outside of the brain when given through the vein. This suggests that pertuzumab and trastuzumab may help shrink or stabilize HER2-positive breast cancer that has spread to the brain in this research study.
In this research study, the investigators are looking to see whether pertuzumab and trastuzumab will work to decrease the size of or stabilize breast cancer that has spread to the brain.
Read the detailed description
Intrathecal administration of pertuzumab and trastuzumab will occur via lumbar puncture (spinal tap) under fluoroscopic guidance by interventional radiology at Duke University Medical Center. The spinal needle will be inserted into the spinal column and 7 mL of cerebrospinal fluid (CSF) will be collected. Once the CSF is removed, the intrathecal pertuzumab and trastuzumab will be administered using aseptic technique. At certain time points the CSF will be analyzed for free cell DNA. If subjects consent, the CSF fluid will also be stored for additional future research.
Patients will be treated using a 3+3 dose-escalation design. Patients will not be accrued to the next cohort (dose escalation) until at least one patient on the previous cohort has been followed for six weeks. If a dose limiting toxicity (DLT) is seen in a patient then the cohort will be expanded by an additional 3 patients to allow for 1 in 6 patients per cohort to have a DLT before dose escalation. Dose limiting toxicity will be assessed weekly during the first six weeks of the treatment.
Patients will be treated weekly for the first six weeks and then every 3 weeks (q21 days). Once the maximum tolerated dose is reached, an additional 12 patients will be enrolled in the cohort at the maximum tolerated dose. The maximum number of enrolled patients is 36. Dosing is as follows: Cohort 1 - 80mg IT trastuzumab, 10mg IT pertuzumab, cohort 2 - 80mg IT trastuzumab, 20mg IT pertuzumab, cohort 3 - 80mg IT trastuzumab, 40mg IT pertuzumab, cohort 4 - 80mg IT trastuzumab, 80mg IT pertuzumab. If the lowest dose level is found to be too toxic, the trial will stop without finding a maximum tolerated dose.
- Conditions
- HER2 Positive Untreated Metastatic Breast Cancer, Asymptomatic or Low Symptomatic Brain Metastasis in Breast Cancer
- Being tested
- Pertuzumab, Trastuzumab
- Keywords
- Breast Cancer, HER2 Positive, HER2+, Brain Metastases, Metastatic Breast Cancer, Intrathecal Treatment, Lumbar Puncture, Pertuzumab, Trastuzumab, Advanced Breast Cancer, Duke University
- Medical subject headings
- Breast Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PertuzumabDrug
Also called Perjeta
Pertuzumab will be administered intrathecally via a lumber puncture. The dosing cohorts are described above in the arm description.
TrastuzumabDrug
Also called Herceptin
Trastuzumab will be administered intrathecally via a lumber puncture. The dosing cohorts are described above in the arm description.
| Study group | Role | What they receive |
|---|---|---|
| Intrathecal Pertuzumab and Trastuzumab | Experimental | Four cohorts will enroll in a dose escalation of pertuzumab and a consistent dose of trastuzumab. The cohorts will be assigned as follows:
Cohort: Intrathecal Dose:
1. 10mg pertuzumab, 80mg trastuzumab
2. 20mg pertuzumab, 80mg trastuzumab
3. 40mg pertuzumab, 80mg trastuzumab
4. 80mg pertuzumab, 80mg trastuzumab Receives: Drug: Pertuzumab; Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as measured by adverse events
Adverse events will be closely monitored and assessed for all subjects on study treatment. The main observational portion of study will be complete at 36 weeks. However, subjects will be allowed to continue on treatment for as long as they are receiving clinical benefit and any adverse events occurring during this time will be assessed. Following discontinuation of study treatment, patient follow-up will take place every 3 months.
Measured: Baseline up to 36 weeks
Maximum tolerated dose as measure by dose limiting toxicity
Toxicity will be graded according to the NCI-CTC version 4 and will be assessed weekly for the first six weeks of treatment and then every 21 days. A DLT is defined as any grade 3 or higher non-hematologic toxicity or grade 4 hematologic toxicity that occurs within the first 6 weeks of treatment that is assessed as possibly related to the intrathecal therapy. Any treatment delays occurring during the first six weeks of treatment that are due to study treatment-related toxicity will also be considered a DLT.
The main portion of study will be complete at 36 weeks. However, subjects will be allowed to continue on treatment for as long as they are receiving clinical benefit.
Measured: Baseline up to 36 weeks
Secondary outcomes (2)
Response rate as measured by brain MRI
Response assessed:
Complete Response (CR): Radiographic complete response (RCR), 100% reduction in tumor, with complete clearing of MRI scan evidence of disease on 2 consecutive scans 6 weeks apart with stable or improved clinical function.
Partial Response (PR): Radiographic stability of disease (RSD), > 50% but < 100% reduction in tumor, with improved clinical function.
Stable Disease (SD): Radiographic stability of disease (RSD), < 50% reduction in tumor or < 25% increase in size of tumor, with stable clinical function.
Progressive Disease (PD): Radiographic progressive disease (RPD), > 25% increase in size of tumor, and/or the presence of declining clinical function attributable to the CNS metastasis. Other indications of progression include development of new CNS metastases or increase in size of previous CNS metastasis. Changes in size of previous CNS metastasis must measure > 25% increase in the largest unidimensional measurement in the absence of new neurologic symptoms.
Measured: Every 6 weeks from Baseline up to 36 weeks
Changes in cell-free circulating tumor DNA (ctDNA) in response to treatment
Measured: Baseline up to 36 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2015 (estimated)
- Study start1 May 2017
- Primary completion22 Feb 2018
- Study completion22 Feb 2018
Why it stopped: Inadequate enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2 Positive Untreated Metastatic 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kimberly Blackwell
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Kimberly Blackwell, Duke University
- Investigators
- Kimberly Blackwell, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02598427
- Sponsor's protocol ID
- Pro00061309
- Status last verified
- Feb 2018
- First submitted
- 4 Nov 2015
- Last updated
- 28 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Escalation Trial of Intrathecal Pertuzumab and Trastuzumab in Patients With New Untreated Asymptomatic or Low Symptomatic Brain Metastasis
- ClinicalTrials.gov ID
- NCT02598427
- Acronym / sponsor ID
- Pro00061309
- Conditions
- HER2 Positive Untreated Metastatic Breast Cancer, Asymptomatic or Low Symptomatic Brain Metastasis in Breast Cancer
- Keywords
- Breast Cancer, HER2 Positive, HER2+, Brain Metastases, Metastatic Breast Cancer, Intrathecal Treatment, Lumbar Puncture, Pertuzumab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inadequate enrollment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Kimberly BlackwellUniversity, hospital or other
- Study start
- 1 May 2017 (actual)
- Primary completion
- 22 Feb 2018 (actual)
- Study completion
- 22 Feb 2018 (actual)
- First posted
- 5 Nov 2015 (estimated)
- Results
- Not posted in the source record
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 well pertuzumab and trastuzumab works in treating breast cancer that has spread to the brain. Pertuzumab and trastuzumab are treatments that stop breast cancer cells from growing abnormally by inhibiting (or blocking) members of a family of proteins that include Human Epidermal Growth Factor Receptor 2 (HER2).
Pertuzumab and trastuzumab have been found to be very effective for HER2-positive breast cancer and are FDA approved for treatment of metastatic breast cancer outside of the brain when given through the vein. This suggests that pertuzumab and trastuzumab may help shrink or stabilize HER2-positive breast cancer that has spread to the brain in this research study.
In this research study, the investigators are looking to see whether pertuzumab and trastuzumab will work to decrease the size of or stabilize breast cancer that has spread to the brain.
Detailed description
Intrathecal administration of pertuzumab and trastuzumab will occur via lumbar puncture (spinal tap) under fluoroscopic guidance by interventional radiology at Duke University Medical Center. The spinal needle will be inserted into the spinal column and 7 mL of cerebrospinal fluid (CSF) will be collected. Once the CSF is removed, the intrathecal pertuzumab and trastuzumab will be administered using aseptic technique. At certain time points the CSF will be analyzed for free cell DNA. If subjects consent, the CSF fluid will also be stored for additional future research.
Patients will be treated using a 3+3 dose-escalation design. Patients will not be accrued to the next cohort (dose escalation) until at least one patient on the previous cohort has been followed for six weeks. If a dose limiting toxicity (DLT) is seen in a patient then the cohort will be expanded by an additional 3 patients to allow for 1 in 6 patients per cohort to have a DLT before dose escalation. Dose limiting toxicity will be assessed weekly during the first six weeks of the treatment.
Patients will be treated weekly for the first six weeks and then every 3 weeks (q21 days). Once the maximum tolerated dose is reached, an additional 12 patients will be enrolled in the cohort at the maximum tolerated dose. The maximum number of enrolled patients is 36. Dosing is as follows: Cohort 1 - 80mg IT trastuzumab, 10mg IT pertuzumab, cohort 2 - 80mg IT trastuzumab, 20mg IT pertuzumab, cohort 3 - 80mg IT trastuzumab, 40mg IT pertuzumab, cohort 4 - 80mg IT trastuzumab, 80mg IT pertuzumab. If the lowest dose level is found to be too toxic, the trial will stop without finding a maximum tolerated dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intrathecal Pertuzumab and Trastuzumab | Experimental | Drug: Pertuzumab, Drug: TrastuzumabFour cohorts will enroll in a dose escalation of pertuzumab and a consistent dose of trastuzumab. The cohorts will be assigned as follows: Cohort: Intrathecal Dose: 1. 10mg pertuzumab, 80mg trastuzumab 2. 20mg pertuzumab, 80mg trastuzumab 3. 40mg pertuzumab, 80mg trastuzumab 4. 80mg pertuzumab, 80mg trastuzumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- HER2 positive by 2013 ASCO-CAP guidelines (IHC 3+ and/or FISH positive; IHC 2+ HER2 patients are eligible with reflex FISH positive testing with the ratio ≥ 2.0) breast cancer patients with untreated asymptomatic or minimally symptomatic brain metastasis by MRI. There is no upper or lower limit to the size or number of brain metastases.
- Patients can have previous brain metastasis that was completely surgically resected if the previously resected lesion is at least 1 cm from target lesion(s) for this study. The location of the previous resection cavity is determined by the post-resection MRI.
- Patients can have previous brain metastasis that was treated with stereotactic radiosurgery (SRS) if the previously treated lesion is at least 1cm from the target lesion(s) for this study. The location of the previous SRS treatment location is determined by the SRS MRI.
- Patients can be on steroids as long as the dose has been stable for ≥ 7 days
- No limitations on prior systemic or intrathecal therapies.
Key exclusion criteria (11 listed)
- No seizures, focal weakness of any extremity (by neurologic exam), or stroke symptoms in the past month.
- No history of prior whole brain radiation.
- No history of lumbar surgery or other pre-existing spinal conditions that would preclude frequent, safe, reliable lumbar punctures.
- No history of serious cardiac arrhythmia or EF < 50%.
- Systemic sites of disease need to be stable on systemic therapy based on the most recent (within 12 weeks) staging scans.
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 |
|---|---|---|
| PertuzumabAlso: PerjetaPertuzumab will be administered intrathecally via a lumber puncture. The dosing cohorts are described above in the arm description. | Drug | Intrathecal Pertuzumab and Trastuzumab |
| TrastuzumabAlso: HerceptinTrastuzumab will be administered intrathecally via a lumber puncture. The dosing cohorts are described above in the arm description. | Drug | Intrathecal Pertuzumab and Trastuzumab |
Primary outcome
Safety as measured by adverse events
Time frame: Baseline up to 36 weeks
Adverse events will be closely monitored and assessed for all subjects on study treatment. The main observational portion of study will be complete at 36 weeks. However, subjects will be allowed to continue on treatment for as long as they are receiving clinical benefit and any adverse events occurring during this time will be assessed. Following discontinuation of study treatment, patient follow-up will take place every 3 months.
Maximum tolerated dose as measure by dose limiting toxicity
Time frame: Baseline up to 36 weeks
Toxicity will be graded according to the NCI-CTC version 4 and will be assessed weekly for the first six weeks of treatment and then every 21 days. A DLT is defined as any grade 3 or higher non-hematologic toxicity or grade 4 hematologic toxicity that occurs within the first 6 weeks of treatment that is assessed as possibly related to the intrathecal therapy. Any treatment delays occurring during the first six weeks of treatment that are due to study treatment-related toxicity will also be considered a DLT. The main portion of study will be complete at 36 weeks. However, subjects will be allowed to continue on treatment for as long as they are receiving clinical benefit.
2 secondary outcomes
Response rate as measured by brain MRI
Time frame: Every 6 weeks from Baseline up to 36 weeks
Changes in cell-free circulating tumor DNA (ctDNA) in response to treatment
Time frame: Baseline up to 36 weeks
Results and safety
The study was stopped early (reason given: Inadequate enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2018.
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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.
Kimberly Blackwell, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pertuzumab and Trastuzumab in people with HER2 Positive Untreated Metastatic Breast Cancer and Asymptomatic or Low Symptomatic Brain Metastasis in Breast Cancer, run by Kimberly Blackwell at 1 site 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 15 inclusion and 11 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: stopped early, as of the sponsor's last update on 28 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Inadequate enrollment). Results are not available in the source record.
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?
Safety as measured by adverse events (time frame: Baseline up to 36 weeks). 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?
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 28 Feb 2018.