E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with ErbB2-positive advanced or metastatic gastric or oesophageal or gastro-oesophageal junction adenocarcinoma. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001150 |
E.1.2 | Term | Adenocarcinoma gastric |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the progression free survival (PFS) in subjects treated with capecitabine and oxaliplatin (CapeOx) plus lapatinib versus CapeOx plus placebo.
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E.2.2 | Secondary objectives of the trial |
For both treatment arms:
-To compare the overall survival (OS) benefit, response rate (RR), and duration of overall response -To compare the rate of clinical benefit (as defined by CR+PR+SD) -To compare the severity and incidence of qualitative and quantitative toxicities -To evaluate and compare the change in health related quality of life (HRQOL) status and symptoms. -To evaluate and compare the changes in unscheduled (not scheduled per protocol) medical resource utilization during treatment and follow-up phases. -To evaluate germline polymorphisms (DNA) of genes targeted by lapatinib plus CapeOx, and those that influence angiogenesis and may be associated with toxicity and/or clinical outcomes in patients with advanced or metastatic gastric adenocarcinoma. -To examine the molecular profiles of tumor tissue, serum and plasma samples to identify factors that may influence biological and clinical responses |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Signed informed consent form
2) Histologically confirmed gastric adenocarcinoma or adenocarcinoma of the oesophagus or gastro-oesophageal junction (for details refer to section 4.2 of protocol)
3) Gastric or oesophageal cancer that is unresectable locally advanced
4) Radiologically evaluable disease, according to RECIST. (scans must have been completed within 28 days prior to registration.)
5) ErbB2 positive status assessed by local lab (IHC 3+ or FISH positive or CISH positive) from the primary or metastatic tumour. Tumour tissue must be supplied from all subjects at study entry and will be sent to the central laboratory for determination of centralised ErbB2 status.
6) Age ≥18 years
7) ECOG Performance status ≤ 2.
8) Adequate organ function assessed within 14 days prior to randomization:
Haematological function: -Absolute neutrophil count ≥ 1.5 x 10^9/L -Heamoglobin ≥ 9g/dL (with transfusion support if needed) -Platelets ≥ 100 x 10^9/L
Hepatic function: -Total bilirubin ≤ 1.5 x upper limit of normal (UNL), or 2.5 x UNL in case of documented Gilberts syndrome -AST/ALT ≤ 3 x UNL, or 5 x UNL in case of documented liver metastases
Renal function: -Serum creatinine ≤ 2.0 mg/dL and -Calculated creatinine clearance ≥ 50 mL/min (Cockcroft-Gault method)
9) Cardiac ejection fraction within institutional range of normal as measured by echocardiogram (ECG) or MUGA scans where an ECG cannot be performed or is inconclusive.
10) Able to swallow and retain oral medications, and/or receive enteral medications via gastrectomy feeding tube, (subjects who are nothing by mouth will be deemed eligible only after review by the study medical monitor).
11) Women and men with potential to have children must be willing to practice acceptable methods of birth control during the study.
12) Prior/Concurrent Therapy
Surgery: -Subjects may have had prior surgery for their gastric cancer. -Patients must be at least 3 weeks beyond surgery and must have recovered from any related toxicity.
Chemotherapy: -More than 5 years since prior chemotherapy for malignancy other than gastric carcinoma -Prior neoadjuvant and/or adjuvant chemotherapy for early stage disease is allowed, provided first cancer recurrence occurred more than 6 months after completion of therapy. One line of treatment in this setting is allowed.
Radiotherapy: -At least 4 weeks since prior radiotherapy. -Concurrent palliative radiotherapy for pain relief is allowed provided radiotherapy is limited to an area other than the sole site of measurable or evaluable disease
Biologic or hormonal therapy: -More than 5 years since prior biological, hormonal or immuno- therapies for malignancy other than gastric carcinoma.
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E.4 | Principal exclusion criteria |
1) Pregnant or lactating females.
2) Known history of active CNS disease.
3) Uncontrolled ascites.
4) Concurrent anti-cancer therapy (chemotherapy, radiation therapy other than for pain relief, immunotherapy, biologic therapy, hormonal therapy or surgery) while taking investigational treatment.
5) Gastric carcinoid, epidermoid, sarcomas, or squamous cell carcinoma.
6) Prior palliative chemotherapy for the treatment of gastric cancer.
7) Prior treatment with oxaliplatin or the regimen CapeOx.
8) Malabsorption syndrome or uncontrolled inflammatory gastrointestinal disease (such as Crohn’s disease or ulcerative colitis).
9) Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure; -Myocardial infarction within past 6 months -New York Association Class III or IV congestive heart failure
10) Pre-existing grade ≥ 2 motor or sensory neuropathy by CTC v3.0.
11) Uncontrolled infection.
12) Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical condition that would interfere with the subject's safety.
13) Current active hepatic or biliary disease.
14) History of other malignancy except: -subjects who have been disease-free for 5 years -subjects with a history of completely resected non-melanoma skin cancer -subjects with successfully treated in situ carcinoma
15) Unresolved or unstable serious toxicity from prior administration of another investigational drug and/or prior cancer treatment.
16. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
17. Known history of pyruvate dehydrogenase (DPD) deficiency.
18. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib, capecitabine, fluorouracil, platins or their excipients.
19. Use of any investigational drug within 30 days prior randomization.
20. Use of concurrent prohibited medications that would interact with study drugs, including herbal remedies and Chinese traditional medicines for cancer, and including any medications or drugs listed in table 1 of section 5.7 of the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (PFS), defined as the time from randomization until the date of progression or death. Date of progression is defined as the date of the first imaging or examination showing disease progression. For patients who are withdrawn from study with no progression, tumor assessments will be continued until progression is documented. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of Life and medical resource utilisation |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |