A randomized, multicenter, open-label study evaluating two different doses of pertuzumab in patients with HER2-positive advanced gastric cancer

Phase 1

• Conditions: HER2-positive adenocarcinoma of the stomach or gastroesophageal junction; MedDRA version: 14.0Level: LLTClassification code 10066896Term: HER-2 positive gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-002331-25-BE
• Lead Sponsor: F. Hoffmann-La Roche Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-09-08
• Last Update Posted: 11 December 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

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/µL (< 2.5 × 109/L)
Absolute neutrophil count (ANC) < 1500/µL (<1.5 × 109/L)
Platelets < 100,000/µL (<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 metastatic site peripherally and

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified