Asymptomatic or Low Symptomatic Brain Metastasis in Breast Cancer Clinical Trial
Official title:
Phase I Dose Escalation Trial of Intrathecal Pertuzumab and Trastuzumab in Patients With New Untreated Asymptomatic or Low Symptomatic Brain Metastasis
| Verified date | February 2018 |
| Source | Duke University |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 1 |
| Est. completion date | February 22, 2018 |
| Est. primary completion date | February 22, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - 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. - 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. Exclusion Criteria: - 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. - 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | Duke University Medical Center | Durham | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Kimberly Blackwell |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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. | Baseline up to 36 weeks | |
| Primary | 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. |
Baseline up to 36 weeks | |
| Secondary | 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. |
Every 6 weeks from Baseline up to 36 weeks | |
| Secondary | Changes in cell-free circulating tumor DNA (ctDNA) in response to treatment | Baseline up to 36 weeks |