A Phase III Study of ErbB2 Positive Advanced or Metastatic Gastric or Esophageal Or Gastroesophageal Junction Adenocarcinoma Treated with Capecitabine Plus Oxaliplatin with or without Lapatinib - N/A

• Conditions: Subjects with ErbB2-positive advanced or metastatic gastric or oesophageal or gastro-oesophageal junction adenocarcinoma.; MedDRA version: 9.1Level: LLTClassification code 10001150Term: Adenocarcinoma gastric

• Registration Number: EUCTR2007-005725-29-NL
• Lead Sponsor: GlaxoSmithKline Research and Development

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-08-13
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 410

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.

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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.

Study & Design

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