Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Phase II Study of ECF-C, IC-C, or FOLFOX-C in Metastatic Esophageal and GE Junction Cancer
Brief Summary: RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving more than one chemotherapy drug (combination chemotherapy) together with cetuximab may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying three different combination chemotherapy regimens to compare how well they work when given together with cetuximab in treating patients with metastatic esophageal cancer or gastroesophageal junction cancer.


Options:
A: Inclusion Criteria:

* Female or male aged 25 or over
* Histological diagnosis of locally advanced or metastatic gastro adenocarcinoma (including adenocarcinoma of the lower third of the oesophagus or the gastro oesophageal junction )
* Radiographically confirmed progression after 1 prior chemotherapy or chemoradiotherapy for gastric cancer. Suitable for and expected to benefit from paclitaxel monotherapy.
* At least one lesion, not previously irradiated, that has baseline at least 10mm in the longest diameter for non nodal lesions and is assessed by Computerised Tomography (CT) or Magnetic Resonance Imaging (MRI)
* Provision of either an archival tumour sample or a fresh tumour sample for confirmation of FGFR2 polysomy/gene amplification

Exclusion Criteria:

* Prior exposure to AZD4547 or history of hypersensitivity other drugs similar in structure or class to AZD4547. Hypersensitivity to paclitaxel or formulated in cremophor EL (polyoxyethylated castor oil)
* Prior taxane treatment for gastric cancer with the exception of adjuvant/neo-adjuvant therapy given \> 6 months; Major surgery, radiotherapy with wide field of radiation or any cancer treatment within 4 weeks before the first dose of the study treatment
* With the exception of alopecia, any unresolved toxicities from prior therapy with a Common Terminology Criteria for AE (CTCAE) grade \>1 at the time of starting study treatment.
* Blood and Echocardiogram (ECG) readings that are deemed to be abnormal by falling outside of the reference ranges in the protocol inclusion/exclusion section.
* Taking other regular medication that are predicted to interact with AZD4547 due to their route of metabolism.
B: Inclusion Criteria:

* Male or female subjects aged greater than or equal to (\>=) 18 years
* Subjects with histologically confirmed recurrent unresectable, recurrent locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction (GEJ)
* Availability of a formalin-fixed, paraffin-embedded (FFPE) block containing tumor tissue
* Subjects must have received 2 prior courses of systemic treatment for unresectable, recurrent, locally advanced or metastatic gastric cancer, and must have progressed after the second line
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at trial entry
* Adequate hematological, hepatic and renal functions defined by the protocol
* Negative blood pregnancy test at Screening for women of childbearing potential.
* Highly effective contraception for both male and female subjects if the risk of conception exists

Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Prior therapy with any antibody or drug targeting T-cell coregulatory proteins
* Concurrent anticancer treatment
* Major surgery
* Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to less than \[\<\] 10 mg prednisone daily).
* All subjects with brain metastases, except those meeting the following criteria: a. Brain metastases have been treated locally, and b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
* Previous malignant disease (other than gastric cancer) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ (bladder,cervical, colorectal, breast)
* Prior organ transplantation, including allogeneic stem-cell transplantation Significant acute or chronic infections
* Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
* Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
* Persisting toxicity of grade \>2 related to prior therapy except neuropathy and alopecia
* Neuropathy Grade greater than or equal (\>=) 3.
* Pregnancy or lactation
* Known alcohol or drug abuse
* History of uncontrolled intercurrent illness including hypertension, active infection, diabetes
* Clinically significant (i.e., active) cardiovascular disease
* All other significant diseases might impair the subject's tolerance of trial treatment
* Any psychiatric condition that would prohibit the understanding or rendering of informed consent and that would limit compliance with study requirements
* Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
* Legal incapacity or limited legal capacity
* Subjects will be excluded from the treatment with irinotecan or paclitaxel monotherapy if administration of their chemotherapy would be inconsistent with the current local labeling (for example, in regard to contraindications, warnings/precautions, or special provisions) for that chemotherapy. Investigators should check updated labeling via relevant websites before randomization
* Subjects should start treatment administration within 28 days after signing the informed consent form (ICF). Treatment administration will start within 4 days after the randomization call
C: 1. Metastatic disease of the esophagus or gastroesophageal junction

   1. Histologic, cytologic or radiologic documentation of metastatic squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction. Radiologic, endoscopic, histologic or cytologic evidence of locally recurrent or locally residual (post-resection) disease is also permitted.
   2. For the purposes of this study, undifferentiated adenocarcinomas and adenosquamous tumors will be considered as adenocarcinomas. In addition, tumors involving the gastroesophageal junction will be defined by the Siewert classification.
   3. Patients with gastroesophageal junction tumors who are eligible:

      * AEG Type I: Adenocarcinoma of the distal esophagus which usually arises from an area with specialized intestinal metaplasia of the esophagus (eg, Barrett's esophagus, and may infiltrate the esophagogastric junction from above).
      * AEG Type II: True carcinoma of the cardia arising from the cardiac epithelium or short segments with intestinal metaplasia at the esophagogastric junction.
   4. Patients with gastroesophageal junction tumors who are NOT eligible:

      * AEG Type III: Subcardial gastric carcinoma which infiltrates the esophagogastric junction and distal esophagus from below.
2. Patients must have at least one paraffin block available (or at least 15 unstained slides for analysis of tumor EGFR status.

   1. Patients with a history of esophageal and GE junction carcinoma treated by surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless an interval of greater than five years has elapsed between the primary surgery and the development of metastatic disease OR the primary cancer was stage I.
   2. Clinicians should consider biopsy of lesions to establish the diagnosis of metastatic esophageal or GE junction carcinoma if there is substantial clinical ambiguity regarding the nature or source of apparent metastases.
3. Patients with Measurable Disease - Lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan.
4. Prior Treatment:

   1. No prior chemotherapy or radiotherapy. No prior therapy which specifically and directly targets the EGF(R) pathway.
   2. No prior allergic reaction to chimerized or murine monoclonal antibody therapy or documented presence of human anti-mouse antibodies (HAMA).
   3. Patients must have completed any major surgery ≥ 4 weeks or any minor surgery ≥ 2 weeks before registration. Patients must have fully recovered from the procedure. Insertion of a vascular access device is not considered major or minor surgery.
   4. No concurrent use of investigational agents is allowed while participating in this study.
5. Patient Characteristics:

   1. ECOG Performance Status of 0-2
   2. ≥ 18 years of age
   3. Patients must be documented to have a stable weight (or less than one pound weight loss) for at least one week prior to registration.
   4. Non-pregnant and not breast-feeding. The effects of cetuximab, cisplatin, epirubicin, fluorouracil, leucovorin, irinotecan, and oxaliplatin on a developing human fetus are not well-known. Because the risk of toxicity in nursing infants secondary to cetuximab, cisplatin, epirubicin, fluorouracil, irinotecan, and oxaliplatin treatment of the mother is unknown but may be harmful, breastfeeding must be discontinued.
6. No myocardial infarction \< 6 months prior to registration or New York Heart Association classification III or IV.
7. No ≥ grade 2 diarrhea within 7 days prior to registration.
8. Patients may not concurrently have any of the following conditions:

   1. Known central nervous system metastases or carcinomatous meningitis
   2. Interstitial pneumonia or symptomatic interstitial fibrosis of the lung
   3. Seizure disorder or active neurological disease requiring anti-epileptic medication
   4. ≥ grade 2 peripheral neuropathy
9. No evidence of Gilbert's Syndrome - Patients with Gilbert's Syndrome may have a greater risk of irinotecan toxicity due to the abnormal glucuronidation of SN-38, the active metabolite of irinotecan. Evidence of Gilbert's Syndrome would include documentation of elevation of indirect bilirubin at any time in the patient's medical history.
10. Required Initial Laboratory Data:

    1. Granulocytes ≥ 1500/µl
    2. Platelet count ≥ 100,000/µl
    3. Creatinine ≤ 1.5 mg/dL
    4. AST (SGOT) ≤ 5.0 x Upper limits of normal
    5. Total bilirubin ≤ 1.5 mg/dL
    6. Albumin ≥ 2.5 grams/dL
D: Inclusion Criteria:

* Recurrent or metastatic gastric cancer that has progressed following first line-therapy
* Confirmed ATM protein status by IHC archival tumour sample
* At least one lesion (measurable and/or non-measurable) that can be accurately assessed by imaging (CT/MRI) at baseline and follow up visits

Exclusion Criteria:

* More than one prior chemotherapy regimen for the treatment of gastric cancer in the metastatic or recurrent setting
* Any previous treatment with a PARP inhibitor, including olaparib
* Patients with second primary cancer, except; adequately treated non melanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for \>5 years

Answer: C