Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled, 2-parallel Group, Phase III Study to Compare Efficacy and Safety of Masitinib 9 mg/kg/Day in Combination With Gemcitabine Compared to Placebo in Combination With Gemcitabine in Treatment of Patients With Advanced/Metastatic Pancreatic Cancer
Brief Summary: The objective of this study is to compare the efficacy and safety of masitinib in combination with gemcitabine to placebo in combination with gemcitabine in patients with advanced/metastatic pancreatic cancer.


Options:
A: Inclusion Criteria:

* Histologically confirmed adenocarcinoma of the pancreas that is surgically inoperable
* Must have had one prior chemotherapeutic regimen for advanced disease (Prior radiation with a radiation sensitizer for locally advanced disease or adjuvant therapy is not considered a prior regimen for purpose of this study)
* Disease must be measurable by RECIST criteria; measurable disease will be defined as at least one lesion that can be accurately measured in at least one dimension measuring at least 2 cm conventional CT or MRI or 1 cm with spiral CT scans (Appendix A)
* Aged 18 years or older
* ECOG performance status of 0 - 2 (see Appendix B)
* Able to take oral medications without difficulty
* Adequate bone marrow function as evidenced by an ANC \> 1500/mL and platelet count \> 100, 000/mL
* Adequate renal function as evidenced by serum creatinine within institutional limits or creatinine clearance \> 60 ml/minute if above upper institutional limits (ULN)
* Adequate hepatic function as evidenced by ALT, AST, and total bilirubin within ULN. If hepatic metastases are present, ALT and AST may be up to 5 x ULN.
* Provision of written informed consent
* Men and women of childbearing potential must be willing to practice acceptable methods of birth control to prevent pregnancy. This is a precautionary measure for use of Gefitinib and docetaxel.

Exclusion Criteria:

* Known severe hypersensitivity to Gefitinib or docetaxel or any of the excipients of these products (i.e. polysorbate 80)
* Previous treatment with Gefitinib or docetaxel.
* Other coexisting malignancies or malignancies diagnosed within the last 5 years, with the exception of basal cell carcinoma or squamous cell carcinoma of the skin or cervical cancer in situ.
* Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital, or St John's Wort
* Treatment with a non-approved or investigational drug within 30 days before Day 1 of trial treatment.
* Treatment with radiation therapy or chemotherapy within 28 days before Day 1 of trial treatment
* Any unresolved chronic toxicity greater then CTC grade 2 from previous anticancer therapy (except alopecia)
* Incomplete healing from previous oncologic or other major surgery.
* Pregnancy or breast feeding (women of childbearing potential).
* Any evidence of clinically active interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded).
* As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease).
* Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial.
B: Inclusion Criteria:

* 18 years old or older
* Histologically or cytologically confirmed diagnosis of metastatic (Stage IV) adenocarcinoma of the pancreas with measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* Performance status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale
* All prior treatment related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) (Version 4.0) ≤ Grade 1 (except alopecia) at the time of randomization
* Adequate baseline organ function
* Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels

Exclusion Criteria:

* Prior systemic therapy (i.e., chemotherapy, immunotherapy, hormone therapy, , targeted therapy or any investigational anti-cancer drug) for metastatic pancreatic adenocarcinoma.

(Prior treatment with 5-FU based or gemcitabine administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed. Prior systemic chemotherapy in the adjuvant setting is allowed ; however, prior therapy with gemcitabine is allowed only if tumor recurrence occurred at least 6 months after completing the last dose of gemcitabine)

* History of another malignancy. Exception: Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Subjects with second malignancies that are indolent or definitively treated may be enrolled. Consult GSK Medical Monitor if unsure whether second malignancies meet requirements specified above
* Any serious and/or unstable pre-existing medical (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator or GSK Medical Monitor
* History of interstitial lung disease or pneumonitis
* History or current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
* Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression
* History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 6 months
C: Inclusion Criteria:

* 18 years of age or older
* Diagnosis of metastatic pancreatic cancer; subjects must have had measurable, or evaluable disease that was histologically confirmed
* Karnofsky performance status of ≥ 60
* Subjects must have failed 1st-line gemcitabine treatment for metastatic pancreatic cancer:

  o An alternate chemotherapeutic agent was an acceptable substitute as 1st-line therapy in the event that the subject was intolerant to or ineligible to receive gemcitabine
* ≥ 2 weeks elapsed from the completion of previous chemotherapy, and subjects must have recovered or been at new stable baseline from any related toxicities

Exclusion Criteria:

* More than 1 prior chemotherapy regimen (not including adjuvant therapy) for metastatic disease
* Evidence of central nervous system (CNS) metastases (unless stable for \> 3 months) or history of uncontrolled seizures
* Ongoing radiation therapy or prior radiation therapy administered as a second-line treatment
* Other active malignancy except basal or squamous carcinoma of the skin
* Inability to swallow food or any condition of the upper GI tract that precluded administration of oral medications
* Inadequate renal, hepatic and bone marrow function demonstrated by clinical observations and/or laboratory assessments
D: Main Inclusion Criteria:

1. Histologically or cytologically confirmed adenocarcinoma of the pancreas
2. Chemo naïve patients with advanced/metastatic disease
3. Documented decision justifying non eligibility for surgical resection. The documentation of the non eligibility for surgical resection will be reviewed by an independent committee.
4. Men and women, age \>18 years
5. Men and women of childbearing potential (entering the study after a confirmed menstrual period and who have a negative pregnancy test), must agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake.
6. Patient should be able and willing to comply with study visits and procedures as per protocol.
7. Patient should understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed.

Main Exclusion Criteria:

1. Patient treated for a cancer other than pancreatic cancer within 5 years before enrollment, with the exception of basal cell carcinoma or in situ cervical cancer
2. Any condition that the physician judges could be detrimental to subjects participating in this study; including any clinically important deviations from normal clinical laboratory values or concurrent medical events Previous treatment
3. Any anti-tumor therapy (any chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy) within 6 months prior to baseline
4. Treatment with any investigational agent within 4 weeks prior to baseline

Answer: D