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

• Register: EUCTR
• Last refreshed on: 31 August 2015
• Main ID: EUCTR2011-002331-25-CZ
• Date of registration: 16/09/2011
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd.
• Public title: A randomized, multicenter, open-label study evaluating two different doses of pertuzumab in patients with HER2-positive advanced gastric cancer
• Scientific title: An Open-Label, Randomized, Multicenter Phase IIa Study Evaluating Pertuzumab in Combination with Trastuzumab and Chemotherapy in Patients with HER2-Positive Advanced Gastric Cancer - JOSHUA
• Date of first enrolment: 16/11/2011
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002331-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Two different dosing schemes of pertuzumab will be compared to each other Number of treatment arms in the trial: 2

Countries of recruitment

Belgium, Czech Republic, European Union, Germany, Italy, Korea, Republic of, Netherlands, Spain

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd.

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd.

Key inclusion & exclusion criteria

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

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

HER2-positive adenocarcinoma of the stomach or gastroesophageal junction
MedDRA version: 14.1 Level: LLT Classification code 10066896 Term: HER-2 positive gastric cancer System Organ Class: 100000004864

Intervention(s)

Product Name: Pertuzumab (rhuMAb 2C4)
Product Code: Ro 436-8451/F01
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Pertuzumab
CAS Number: 380610-27-5
Current Sponsor code: RO4368451
Other descriptive name: rhuMAb 2C4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 420 mg/14ml-

Trade Name: Herceptin®
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: TRASTUZUMAB
CAS Number: 180288-69-1
Current Sponsor code: Ro 45-2317
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 43

Secondary Objective: To make an exploratory assessment of the anti-tumor activity of pertuzumab in combination with trastuzumab and chemotherapy in patients with HER2 positive inoperable locally advanced or recurrent and/or metastatic adenocarcinoma of the stomach or gastroesophageal junction

Main Objective: • To estimate the minimum (trough) pertuzumab concentration
(Cmin) at Day 43 for two dose levels of pertuzumab in order to
identify a dose that produces a steady-state Cmin of = 20 µg/mL in 90% of patients receiving pertuzumab and trastuzumab plus chemotherapy as first-line treatment for HER2-positive inoperable locally advanced or recurrent and/or metastatic adenocarcinoma of the stomach or gastroesophageal junction
• To evaluate the safety and tolerability of two dose levels of pertuzumab in combination with trastuzumab and chemotherapy administered every 3 weeks to patients with HER2-positive inoperable locally advanced or recurrent and/or metastatic adenocarcinoma of the stomach or gastroesophageal junction

Primary end point(s): Minimum (trough) serum concentration (Cmin) for pertuzumab

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: End of cyles 3 and 6

Secondary end point(s): This study is not designed or powered to provide an accurate evaluation of efficacy. Thus, efficacy analyses are exploratory and no comparisons between dose levels will be made. Investigator-assessed tumor response will be used to summarize best overall response at the end of Cycles 3 and 6 for each treatment arm, defined as patients with a complete or partial response as determined by RECIST.

Secondary ID(s)

2011-002331-25-DE

BP27836

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd.