The investigators would like to keep track of the patient's medical condition indefinitely. The investigators would like to do this either by seeing the patient in clinic or by contacting the patient and the patient's primary doctor periodically to see how the patient is doing. Keeping in touch with the patient and checking the patient's condition periodically helps the investigators look at the long-term effects of the research study.
The dose for subsequent dose levels will be determined according to the treatment-related AE observed during the cycle 1 21 days in the previous dose level Drug: ARRY Twice Daily Dosage ARRY will be administered daily either twice-daily along with concurrent administration of trastuzumab on Day 1.
The dose for subsequent dose levels will be determined according to the treatment-related AE observed during the cycle 1 21 days in the previous dose level Drug: ARRY Once Daily ARRY will be administered daily once-daily along with concurrent administration of trastuzumab on Day 1.
Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. Try the modernized ClinicalTrials. Learn more about the modernization effort.
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Federal Government. Read our disclaimer for details. Last Update Posted : December 28, Study Description. The purpose of this study is to test the safety of different doses of ARRY in combination with trastuzumab.
However, the combination of ARRY and trastuzumab has not yet been tested. It is thought that ARRY and trastuzumab might work together because they attach to different parts of the HER2 receptor and prevent it from functioning. Because HER2 positive breast cancer contains high levels of HER2 receptor, but normal cells in your body generally do not, the drugs may be able to "target" the cancer cells.
In addition, in laboratory studies, ARRY appears to have some penetration into the brain. Show detailed description. Hide detailed description.
Detailed Description:. At the start of each cycle the patient will have: A medical history, which includes questions about health, current medications, and any allergies. Performance status, which evaluates the ability to carry on with usual activities. Physical examination, the doctor will examine the patient body, including measuring height, weight, and vital signs blood pressure, body temperature, pulse rate and breathing rate.
A neurological examination to asses any neurological symptoms for example, difficulties with balance Blood tests will be drawn at the beginning of each study treatment cycle for tests to monitor the function of liver and kidneys and to check blood cell counts. In addition, blood tests will be drawn on days 4, 8, and 15 of the first cycle of study treatment to monitor liver function. Periodically the patient will undergo: The patient will have a brain MRI every two cycles.
If the brain scans are stable or improved after the patient has been on the study for 6 months or longer, the frequency of your body scans will be decreased to once every 4 cycles. The patient will also have CT or MRI scans of the body at the end of cycle 2, cycle 4 and every 4 cycles thereafter.
The research doctor may ask the patient to have a bone scan at the same time points if this is clinically indicated. Electrocardiogram EKG , which shows the electrical activity of the heart. It will be performed on Day 1 of cycle 2. This will be performed every months. Arms and Interventions. Outcome Measures. Secondary Outcome Measures : Incidence of clinical lab abnormalities hematology, chemistry, liver function tests, coagulation, urinalysis [ Time Frame: Up to approximately 4 years ] Severity of clinical lab abnormalities hematology, chemistry, liver function tests, coagulation, urinalysis [ Time Frame: Up to approximately 4 years ] Frequency of dose reductions in tucatinib ONT [ Time Frame: Up to approximately 4 years ] Frequency of dose reductions in capecitabine [ Time Frame: Up to approximately 4 years ] Plasma concentrations of tucatinib ONT and metabolite [ Time Frame: 26 months ] Plasma concentrations of capecitabine and metabolites [ Time Frame: 26 months ] Objective response rate ORR [ Time Frame: 26 months ] Objective response OR will be defined as a best response of complete response CR or partial response PR.
PFS will be defined as the time from first dose of study drug until documentation of disease progression or death from any cause. Eligibility Criteria. Information from the National Library of Medicine Choosing to participate in a study is an important personal decision. Progressive disease, with a history of prior treatment with both trastuzumab and T-DM1 unless deemed intolerant to or ineligible for T-DM1 by the investigator for metastatic disease.
If female and of child-bearing potential, has negative pregnancy test within 14 days prior to treatment. If a sexually active male or a sexually active female of child-bearing potential, agrees to use dual two concurrent forms of medically accepted contraception from the time of consent until 6 months after the last dose of ONT, capecitabine, or trastuzumab, whichever is longest.
Left ventricular ejection fraction LVEF must be within institutional limits of normal as assessed by echocardiogram ECHO or multiple-gated acquisition scan MUGA documented within 4 weeks prior to first dose of study drug. Exclusion Criteria Medical, social, or psychosocial factors that, in the opinion of the Investigator, could impact safety or compliance with study procedures. Patient is breastfeeding. Previous treatment with any experimental agent within 14 days or five half-lives of study treatment, whichever is greater.
Previous treatment with trastuzumab or other antibody-based therapy within three weeks of starting study treatment or with chemotherapy or hormonal cancer therapy within two weeks of starting study treatment. Previous treatment with: Capecitabine for metastatic disease at any time, for patients assigned to cohorts using capecitabine plus ONT Combination 1 or capecitabine plus trastuzumab plus ONT Combination 3. However, patients who have previous treatment with capecitabine for metastatic disease are eligible for enrollment into cohorts using trastuzumab plus ONT Combination 2.
Patients who have received capecitabine for adjuvant or neoadjuvant treatment at least 12 months prior to starting study treatment are eligible to enroll into all cohorts Combination 1, 2, or 3. Any small molecule HER2 inhibitors including but not limited to lapatinib, neratinib, or afatinib within the last 4 weeks prior to initiation of study therapy. CNS disease: Patients with leptomeningeal disease are excluded.
Dose escalation and expansion cohorts: Patients with symptomatic CNS metastases are excluded. Patients with treated CNS metastases or untreated asymptomatic CNS metastases not requiring immediate local therapy may be eligible.
Enrollment of patients with metastases must be approved by the study medical monitor. Optional CNS disease expansion cohorts: Patients with untreated asymptomatic CNS metastases not requiring immediate local therapy or patients with progressive CNS disease following local therapy may be eligible with medical monitor approval.
History of allergic reactions to compounds of similar chemical or biological composition to capecitabine for patients assigned to Combination 1 or 3 only , trastuzumab for patients assigned to Combination 2 or 3 only , or ONT, except for a history of Grade 1 or Grade 2 Infusion Related Reaction to trastuzumab, which has been successfully managed. Patients with uncorrectable electrolyte abnormalities.
Known to be HIV positive. HIV testing is not required for those patients who are not known to be positive. Known liver disease, autoimmune hepatitis, or sclerosing cholangitis. Inability to swallow pills or any significant gastrointestinal diseases, which would preclude adequate absorption of oral medications.
Primary Outcome Measures : Characterize the safety profile of the study drug in terms of adverse events, clinical laboratory tests and electrocardiograms. Secondary Outcome Measures : Characterize the pharmacokinetics of the study drug. Eligibility Criteria. Information from the National Library of Medicine Choosing to participate in a study is an important personal decision. Additional criteria exist. Key Exclusion Criteria Part 1 and Part 2 : Uncontrolled or symptomatic brain metastases patients may be considered adequately controlled if on a stable steroid dose for at least 30 days.
Treatment with an investigational medicinal product or device within 30 days prior to first dose of study drug. Radiotherapy within 28 days prior to first dose of study drug not including palliative radiotherapy at focal sites. Chemotherapy within 21 days prior to first dose of study drug. Major surgery within 30 days prior to first dose of study drug. Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials. More Information. Layout table for additonal information Responsible Party: Seagen Inc.
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