A Phase 1 and Pharmacologic Study of MM-111 in Combination With Multiple Treatment Regimens in Patients With Advanced HER2 Positive Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 15
- 主要终点
- Determine patient's safety (# of adverse events/serious adverse events) and tolerability of MM-111 in combination with multiple treatment regimens
研究概览
简要总结
This study is an open-label, dose-escalation study of MM-111 with five different combination treatments with the main goal of determining the safety of MM-111 with each combination.
详细描述
To determine the MTD and any DLT of MM 111 when administered in combination with either 1) cisplatin, capecitabine, and trastuzumab; 2) lapatinib +/- trastuzumab; 3) paclitaxel and trastuzumab 4) lapatinib, paclitaxel and trastuzumab or 5) docetaxel and trastuzumab in patients with human epidermal growth factor receptor (HER2+) solid tumors
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Patients for whom potentially curative antineoplastic therapy is available
- •Patients who are pregnant or lactating
- •Patients with an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing. (At the discretion of the Investigator, patients with tumor fever may be enrolled.)
- •Patients with untreated and/or symptomatic primary or metastatic central nervous system (CNS) malignancies (Patients with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable dose of corticosteroids for at least 2 weeks prior to the first scheduled day of dosing will be eligible for the trial.)
- •Patients with known hypersensitivity to any of the components of MM-111 or who have had hypersensitivity reactions to fully human monoclonal antibodies.
- •Patients with a known history of hypersensitivity to any of the drug components of a particular regimen.
- •Patients who have received other recent antitumor therapy including:
- •Investigational therapy administered within the 28 days prior to the first scheduled day of dosing MM-
- •Dosing in < 28 days since receiving investigational therapy is acceptable once a time interval equal to at least five half-lives of the investigational agent have passed.
- •Any standard chemotherapy or radiation within 14 days (and having passed the time of any actual or anticipated toxicities) prior to the first scheduled dose of MM-
- •There is no necessary washout for trastuzumab. Patients enrolled to the lapatinib-containing arms of the study do not need to have a washout period for lapatinib.
- •Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 50%
- •History of myocardial infarction within 12 months of enrollment
- •Uncontrolled hypertension (systolic blood pressure >180 mm Hg or diastolic blood pressure >100 mm Hg)
- •Known angina pectoris requiring medication
- •Known clinically significant valvular heart disease
- •Known history of high-risk arrhythmias
- •Known history of congestive heart failure
- •Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
- •Active gastrointestinal bleedingPatients who have received prior maximum cumulative anthracycline doses:
- •doxorubicin or liposomal doxorubicin doses > 360 mg/m2
- •mitoxantrone > 120 mg/m2 and idarubicin > 90 mg/m2
- •epirubicin doses higher than 720 mg/m2
- •Other (e.g., liposomal doxorubicin or other anthracycline equivalent of 360 mg/m2 of doxorubicin)
- •If more than 1 anthracycline has been used, the cumulative dose must not exceed the equivalent of 360mg/m2 of doxorubicin
- •Patients with a history of allogeneic transplant. (Patients with a history of autologous bone marrow or stem cell transplant may be enrolled.)
- •Patients with known human immunodeficiency virus (HIV), hepatitis B or C. (If patients have previously been treated for hepatitis C and have undetectable viral loads, they can be considered eligible for the trial.)
- •Patients with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
研究组 & 干预措施
Arm 1
Regimen follows a 3-week treatment cycle.
Cisplatin 80mg/m2 given on day 1 by IV infusion over two hours every three weeks.
Capecitabine 1000 mg/m2 given orally twice daily for fourteen days each 3-week cycle.
Up to six 3-week cycles of Cisplatin and Capecitabine to be administered. Trastuzumab given as 8 mg/kg loading dose at week 1 over 90 minutes followed by 6 mg/kg every 3 weeks over 30-90 minutes.
MM-111 will be administered over 90 minutes for the first infusion and then weekly over 60 minutes thereafter.
Trastuzumab (every 3 weeks) and MM-111 (weekly) will continue until disease progression, unacceptable toxicity, or withdrawal of consent.
干预措施: Cisplatin, Capecitabine, Trastuzumab and MM-111 (Drug)
Arm 2
Regiment follows a 4-week treatment cycle.
The following Lapatinib and Trastuzumab regimen will be given in combination with MM-111 in the following order:
- Trastuzumab 4 mg/kg loading dose week 1 over 90 minutes
- Followed by Trastuzumab 2 mg/kg weekly thereafter
- Lapatinib 1000 mg by mouth (PO) daily
- MM-111 will be administered over 90 minutes for the first infusion and then weekly over 60 minutes thereafter
Treatment with this regimen will be continued until disease progression, unacceptable toxicity, or withdrawal of consent.
干预措施: Lapatinib +/- Trastuzumab and MM-111 (Drug)
Arm 3
Regimen follows a 4-week treatment cycle Paclitaxel dosing should begin first dose on cycle 1 day 1. Paclitaxel will be administered at 80 mg/m2 weekly, as an IV infusion over 60 minutes. The infusion should be prepared as directed in the Paclitaxel package insert. All patients receiving Paclitaxel should be premedicated as per the local institutional guidelines.
Trastuzumab will be administered via IV over 90 minutes at a 4 mg/kg loading dose for the first infusion followed by weekly infusion of 2 mg/kg over 60 minutes thereafter.
MM-111 will be administered over 90 minutes for the first infusion and then weekly over 60 minutes thereafter.
Treatment with this regimen will be continued until disease progression, unacceptable toxicity, or withdrawal of consent.
干预措施: Paclitaxel, Trastuzumab and MM-111 (Drug)
Arm 4
4-week treatment cycle. Lapatinib given orally. Paclitaxel dosing on cycle 1 day 1. Paclitaxel given at 80 mg/m2 weekly, as an IV infusion over 60 minutes. The infusion should be prepared as directed in the Paclitaxel package insert. All patients receiving Paclitaxel should be premedicated as per the local institutional guidelines.
Trastuzumab given via IV over 90 minutes at a 4 mg/kg loading dose for the first infusion followed by weekly infusion of 2 mg/kg over 60 minutes thereafter.
MM-111 given over 90 minutes for the first infusion and then weekly over 60 minutes thereafter.
Treatment with this regimen will be continued until disease progression, unacceptable toxicity, or withdrawal of consent.
干预措施: Lapatinib, trastuzumab, paclitaxel, and MM-111 (Drug)
Arm 5
Docetaxel, trastuzumab and MM-111 3-week treatment cycles with therapies given in the following order: 1) docetaxel, 2) trastuzumab, and 3) MM-111
Docetaxel given as an IV infusion over 60 minutes every three weeks. The infusion should be prepared as directed in the Docetaxel package insert and any institutional guidelines. All patients receiving Docetaxel should be pre-medicated as per the local institutional guidelines.
The first dose of trastuzumab is a loading dose of 8 mg/kg administered over 90 minutes followed by every three week dosing at 6 mg/kg over 60 minutes via IV infusion.
The first dose of MM-111 given over 90 minutes followed by 3 week dosing over 60 minutes in the absence of infusion-related reactions
干预措施: Docetaxel, trastuzumab and MM-111 (Drug)
结局指标
主要结局
Determine patient's safety (# of adverse events/serious adverse events) and tolerability of MM-111 in combination with multiple treatment regimens
时间窗: 30 months
To determine the maximum tolerated dose (MTD) and any dose limiting toxicity (DLT) of MM-111 when administered in combination with either 1. cisplatin, capecitabine, and trastuzumab; 2. lapatinib +/- trastuzumab; 3. paclitaxel and trastuzumab 4. lapatinib, paclitaxel, trastuzumab; or 5. docetaxel and trastuzumab in patients with HER 2 positive solid tumors
次要结局
- To characterize the pharmacokinetics (PK) profile of MM-111 when administered in combination with multiple treatment regimens. The PK profile will help to determine the phase 2 dose(33 months)
- To establish the recommended Phase 2 dose(s) of MM-111 when administered in each of the combinations assessed (based on PK profile, safety data and overall patient tolerability)(33 months)