Clinical trial: Varlitinib in Combination With mFOLFOX6 for Advanced or Metastatic Gastric Cancer (First Line) (NCT03130790)

Eligibility criteria:
Inclusion Criteria - Phase 2 Part

          1. Subjects of respective country's legal age or older at the time of written informed
             consent.

          2. Subjects with histologically confirmed inoperable locally advanced, recurrent, or
             metastatic adenocarcinoma of the stomach or GEJ cancers may include Siewert Class I,
             II, or III types.

          3. Mandatory provision of an unstained, archived tumor tissue sample in a quantity
             sufficient to allow for local lab analysis of HER1 and HER2 expression status. If
             archived tumor tissue is not available, subject must agree to undergo fresh core
             biopsy to obtain adequate tumor tissue

          4. Subjects with tumors with IHC evidence of expression of HER1 (at level of + or ++ or
             +++) and HER-2 (at level of +, or ++) using standard criteria in the local lab.
             Subjects with HER-2 over expression at level of +++ determined by IHC and subject
             confirmed HER2 2+ by IHC with HER2 gene amplification confirmed by FISH but has
             contradiction to trastuzumab*.

             *For details of contraindication related to trastuzumab, refer to package insert or US
             treatment guideline.

          5. Have radiographically measurable disease as defined by RECIST v1.1

          6. Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

          7. Estimated life expectancy of more than 4 months

          8. Able to swallow and retain oral medication

          9. Subject with adequate organ and hematological function:

             d) Hematological function, as follows: i. Absolute neutrophil count (ANC) ≥1.5 x 109/L
             ii. Platelet count ≥ 100 x 109/L iii. HgB≥9 g/dL (packed red cell blood transfusions
             are not allowed within one week prior to baseline hematology profile).

             e) Renal functions, as follows: i. Serum creatinine ≤1.5x upper limit of normal (ULN)
             or estimated glomerular filtration rate (eGFR)> 60 mL/min/1.73m2 f) Hepatic function,
             as follows: i. Total bilirubin ≤1.5 x ULN ii. AST and ALT ≤2.5 x ULN (or ≤5 x ULN in
             subjects with liver metastasis) iii. Albumin ≥25 g/L

         10. Negative serum human chorionic gonadotropin (HCG)/ or urine pregnancy test within 7
             days prior to randomization for premenopausal women of reproductive capacity and for
             women 12 months after menopause

         11. Willingness to use highly effective birth control method (failure rate <1%) while on
             study.

        Inclusion Criteria - Phase 3 Part

          1. Subjects of respective country's legal age or older at the time of written informed
             consent.

          2. Subjects with histologically confirmed inoperable locally advanced, recurrent, or
             metastatic adenocarcinoma of the stomach or GEJ cancers may include Siewert Class I,
             II, or III types.

          3. Mandatory provision of an unstained, archived tumor tissue sample in a quantity
             sufficient to allow for local lab analysis of HER1 and HER2 expression status. If
             archived tumor tissue is not available, subject must agree to undergo fresh core
             biopsy to obtain adequate tumor tissue.

          4. Subjects with tumors with IHC evidence of expression of HER1 (at level of + or ++ or
             +++) and HER-2 (at level of +, or ++) using standard criteria in the local lab.
             Subjects with HER-2 over expression at level of +++ determined by IHC and subject
             confirmed HER2 2+ by IHC with HER2 gene amplification confirmed by FISH but has
             contradiction to trastuzumab*.

          5. Note: *For details of contraindication related to trastuzumab, refer to package insert
             or US treatment guideline

          6. Subjects with ECOG performance status of 0 to 1

          7. Able to swallow and retain oral medication

          8. Subject with adequate organ and hematological function:

             a) Hematological function, as follows: i. Absolute neutrophil count (ANC) ≥1.5 x 109/L
             ii. Platelet count ≥100 x 109/L iii. HgB≥9 g/dL (packed red cell blood transfusions
             are not allowed within one week prior to baseline hematology profile).

             b) Renal functions, as follows: i. Serum creatinine ≤ 1.5x ULN or eGFR> 60
             mL/min/1.73m2 c) Hepatic function, as follows: i. Total bilirubin ≤1.5 x ULN ii. AST
             and ALT ≤2.5 x ULN (or ≤5 x ULN in subjects with liver metastasis) iii. Albumin ≥25
             g/L

          9. Negative serum human chorionic gonadotropin (HCG)/ or urine pregnancy test within 7
             days prior to randomization for premenopausal women of reproductive capacity and for
             women 12 months after menopause

         10. Willingness to use highly effective birth control method (failure rate <1%) while on
             study.

        Exclusion Criteria:

          1. Subject with HER-2 over expression at level of +++ determined by IHC or subject
             confirmed HER2 2+ by IHC with HER2 gene amplification confirmed by Fluorescence in
             situ hybridization (FISH) in the central lab.

          2. Prior systemic anti-cancer treatment for inoperable locally advanced, recurrent, or
             metastatic adenocarcinoma of the stomach or GEJ. However, previous neo adjuvant
             chemotherapy is allowed if subject has progression of disease more than 6 months after
             neoadjuvant treatment.

          3. Subjects have undergone major surgery within 28 days prior to randomization

          4. Subject with brain lesion, known brain metastases (unless previously treated and well
             controlled for a period of at least 4weeks).

          5. Subject with malabsorption syndrome, diseases significantly affecting gastrointestinal
             function, extensive resection of the stomach or small bowel, or difficulty in
             swallowing and retaining oral medications.

          6. Subjects with an uncontrolled intercurrent illness including, but not limited to,
             ongoing or active infection, New York heart Association class III or IV congestive
             heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia,
             diabetes, hypertension, or psychiatric illness/social situations that would limit
             compliance with study requirements.

          7. Subjects with any history of other malignancy unless in remission for more than 1
             year. (Nonmelanoma skin carcinoma and carcinoma-in-site of uterine cervix treated with
             curative intent is not exclusionary).

          8. Female subjects who are pregnant or breast feeding.

          9. Subjects who were previously treated with varlitinib.

         10. Subjects who took other investigational drugs and/or used investigational medical
             devices or have undergone major surgery within 28 days before initiating varlitinib
             therapy.

         11. Are currently on or have received anti-cancer therapy, radiation or local treatment
             within the past 28 days

         12. Subject with unresolved or unstable serious toxicity (≥ CTCAE 4.03 Grade 2) from prior
             administration of another investigational drug and/or prior cancer treatment(excluding
             hair loss)

         13. Subjects with a known history of human immunodeficiency virus (HIV), decompensated
             cirrhosis, hepatitis B infection with hepatitis B virus DNA exceeding 2000 IU/mL or
             hepatitis C (treatment naïve or after treatment without sustained virologic response).

         14. Known history of drug addiction within the past 1 year.

         15. Subjects who need continuous treatment with proton pump inhibitors during the study
             period.

         16. Any history or presence of clinically significant cardiovascular, respiratory,
             hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic,
             neurologic or psychiatric disease or any other condition which in the opinion of the
             Investigator could jeopardize the safety of the subject or the validity of the study
             results.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 21 Years old.


Patient description (medical language): A 63-year-old man comes to the clinic for recent unintentional weight loss. The patient also has epigastric discomfort after meals. He has no known medical problems and takes no medications. His blood pressure is 130/75 and pulse rate is 88/min. He is not febrile. Upper endoscopy shows a lesion in the stomach that shows typical features of diffuse-type adenocarcinoma presenting with signet ring cells that do not form glands.

Patient description (patient's own words): I went to the clinic because I had been losing so much weight that it was concerning. I'm a 63-year-old guy, and it is something rather unusual. I'm always suffering from stomachache after every meal. I've never been sick, and I don't take any medicine. The doctor took my blood pressure and told me it was 130/75, and my pulse rate was 88/min. I'm not febrile! I also had to do an endoscopy, and they found a lesion in my stomach that shows typical features of stomach cancer. I'm totally devastated...

Does the patient match the trial criteria? Entailment