An Open-Label, Randomized, Multicenter Phase IIa Study;Evaluating Pertuzumab in Combination with Trastuzumab and;Chemotherapy in Patients with HER2-Positive Advanced;Gastric Cancer
- Conditions
- gevorderde maligniteiten in gastro-oesopageale overgang of maagadenocarcinomagastric cancer
- Registration Number
- NL-OMON35408
- Lead Sponsor
- Roche Nederland B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 12
Disease-Specific Inclusion Criteria;* Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction with inoperable locally advanced or metastatic disease, not amenable to curative therapy. Patients with advanced disease who present with a recurrence post operatively (when intent of surgery was cure) are also eligible for entry.;* Measurable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST), v1.1, assessed using imaging techniques (CT or MRI), or non-measurable disease that can be followed;* HER2 positive tumor defined as either IHC 3+ or IHC 2+ in combination with ISH +, as assessed by central laboratory on primary or metastatic tumor ISH positivity is defined as a ratio of ><= 2.0 for the number of HER2 gene copies to the number of signals for CEP17.;Availability of formalin-fixed paraffin-embedded (FFPE) tissue with at least 5 mm of invasive tumor for central confirmation of HER2 eligibility is mandatory.;* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;* Baseline LVEF ><= 55% (measured by ECHO or MUGA) ;* Life expectancy of at least 3 months.;General Inclusion Criteria;* Male or female;* Age ><= 18 years;* Signed informed consent;* For women of childbearing potential and male participants with partners of childbearing potential: agreement to use a highly effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by the patient and/or partner (see Section 7.2.6 for details). Contraception use must continue for the duration of study treatment and for at least 6 months after the last dose of study medication.
Cancer-Related Exclusion Criteria;* Previous chemotherapy for advanced or metastatic disease, except that prior adjuvant or neoadjuvant therapy is allowed if at least 6 months has elapsed between completion of adjuvant or neoadjuvant therapy and enrollment in the study. Adjuvant or neoadjuvant treatment with platinum-based therapy is not allowed.;* Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome (e.g., patients with partial or total gastrectomy can enter the study, but not those with a jejunostomy probe);* Active (significant or uncontrolled) gastrointestinal bleeding;* Residual relevant toxicity resulting from previous therapy (e.g., neurological toxicity of >= Grade >= 2 [NCI CTCAE]), with the exception of alopecia;* Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal cell carcinoma.;Exclusion Criteria Related to Hematological, Biochemical, and Organ Function;* Any of the following abnormal laboratory tests immediately prior to randomization: ;Serum total bilirubin > 1.5 times the upper limit of normal (ULN) or, for patients with known Gilberts syndrome, serum total bilirubin > 2 × ULN;For patients with no liver and no bone metastases: ;AST or ALT > 2.5 × ULN, and alkaline phosphatase (ALP) > 2.5 × ULN;In patients with liver metastases and no bone metastases: ;AST or ALT > 5 × ULN, and ALP > 2.5 × ULN;In patients with liver metastases and bone metastases: ;AST or ALT > 5 × ULN, and ALP > 10 × ULN;;In patients with bone metastases and no liver metastases: ;AST or ALT > 2.5 × ULN, and ALP > 10 × ULN ;Albumin < 25 g/L;Creatinine clearance < 60 mL/min;Total WBC count < 2500/*L (< 2.5 × 109/L);Absolute neutrophil count (ANC) < 1500/*L (<1.5 × 109/L);Platelets < 100,000/*L (<100 × 109/L).;Other Study Drug*Related Exclusion Criteria;* Serious cardiac illness or medical conditions including but not confined to:;History of documented heart failure or systolic dysfunction (LVEF < 50%);High-risk uncontrolled arrhythmias, such as atrial tachycardia with a heart rate >= 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV block (second-degree AV block Type 2 [Mobitz II] or third-degree AV block);Angina pectoris requiring anti-anginal medication;Clinically significant valvular heart disease;Evidence of transmural infarction on ECG;Poorly controlled hypertension (e.g., systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg);* Dyspnea at rest due to complications of advanced malignancy or other disease, or requirement for supportive oxygen therapy;* Treatment with chronic or high-dose corticosteroid therapy.;Inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are allowed.;* Clinically significant hearing abnormality;* Known dihydropyrimidine dehydrogenase deficiency.;General Exclusion Criteria;* History or clinical evidence of brain metastases;* Serious uncontrolled systemic intercurrent illness (e.g., infections or poorly controlled diabetes);* Pregnant or lactating. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization, irrespective of the method of contraception used.;* Radiotherapy within 4 weeks prior to start of study treatment, or within 2 weeks prior to start of study treatment if palliative radiotherapy is given to bone meta
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To estimate the minimum (trough) pertuzumab concentration (Cmin) at Day 43 for<br /><br>two dose levels of pertuzumab in order to identify a dose that produces a<br /><br>steady-state Cmin of *20 *g/mL in 90% of patients receiving pertuzumab and<br /><br>trastuzumab plus chemotherapy as first-line treatment for HER2-positive<br /><br>inoperable locally advanced or recurrent and/or metastatic adenocarcinoma of<br /><br>the stomach or gastroesophageal junction.<br /><br>To evaluate the safety and tolerability of two dose levels of pertuzumab in<br /><br>combination with trastuzumab and chemotherapy administered every 3 weeks to<br /><br>patients with HER2-positive inoperable locally advanced or recurrent and/or<br /><br>metastatic adenocarcinoma of the stomach or gastroesophageal junction</p><br>
- Secondary Outcome Measures
Name Time Method <p>To make an exploratory assessment of the anti-tumor activity of pertuzumab in<br /><br>combination with trastuzumab and chemotherapy in patients with HER2-positive<br /><br>inoperable locally advanced or recurrent and/or metastatic adenocarcinoma of<br /><br>the stomach or gastroesophageal junction.</p><br>