Pazopanib or Pemetrexed and Crizotinib in Advanced Cancer

Inclusion Criteria:

1. Patients with advanced cancer, either refractory to standard therapy or for which no effective standard therapy that increases survival for at least 3 months is available.
2. Patients must have measurable or evaluable disease, as defined by RECIST 1.1.
3. Women of child-bearing potential and men must agree to use adequate contraception.
4. ECOG performance status of 0 to 2.
5. Adequate organ functions: (Crizotinib plus Pazopanib arm A): Neutrophils \> 1000/uL; Platelets ≥ 75,000/uL; Total bilirubin \< or= 2 x ULN (upper limit of normal); ALT \< or = 2.5 x ULN or \< o r= 5 x ULN if liver metastases persist; Serum creatinine \< 2 x ULN (Crizotinib plus Pemetrexed arm B, Pazopanib plus Pemetrexed arm C, Crizotinib plus Pazopanib plus Pemetrexed arm D) Neutrophils \> 1500/uL; Platelets \> or = 100,000/uL; Total bilirubin \< or = 2 x ULN (upper limit of normal); ALT \< or = 2.5 x ULN or \< or = 5 x ULN if liver metastases persist; Calculated GFR \> 45 mL/min.
6. Creatinine Clearance: The standard Cockcroft and Gault formula must be used to calculate CrCl for enrollment or dosing. Also include in the pre-treatment or baseline text portion of the protocol, the 'On Study Evaluations or During Treatment' for every Pemetrexed treatment day, and also capture in the study Schedule of Events. No dosage adjustment is needed in patients with creatinine clearance \> 45 mL/min. Insufficient numbers of patients have been studied with creatinine clearance \<45 mL/min to give a dose recommendation. Therefore, Pemetrexed should not be administered to patients whose creatinine clearance is \<45 mL/min.
7. For pemetrexed arms: The ability to interrupt NSAIDs 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of Pemetrexed.
8. The ability to take folic acid, Vitamin B12, and dexamethasone according to protocol for all pemetrexed arms.
9. Expansion cohort only for arms containing crizotinib: arm A (Crizotinib plus Pazopanib) and arm B (Crizotinib plus Pemetrexed) and arm D (Crizotinib plus Pazopanib Plus Pemetrexed) but not arm C (Pazopanib plus Pemetrexed). Patients must have ALK abnormality including: translocation, ALK amplification, mutation and overexpression as determined by FISH, IHC, qPCR, qRT-PCR, array Comparative Genomic Hybridization or direct sequencing (aCGH). Or patients must have a c-Met abnormality; either c-Met amplification or c-Met mutation or patients must have the ROS1 translocation as determined by FISH.

Exclusion Criteria:

1. Patient receiving any concurrent chemotherapy.
2. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics.
3. Symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris or congenital long QT syndrome.
4. Medical and/or psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk.
5. Known anaphylactic or severe hypersensitivity to study drugs or their analogs.
6. Patient has failed to recover from any prior surgery within 4 weeks of study entry.
7. Patient is pregnant or lactating.
8. Patient has had any treatment specific for tumor control within 3 weeks of dosing with investigational drugs and cytotoxic agents, or within 2 weeks of cytotoxic agent given weekly, or within 6 weeks of nitrosoureas or mitomycin C, or within 5 half-lives of biological targeted agents with half-lives and pharmacodynamic effects lasting less than 5 days (that includes, but is not limited to, erlotinib, sorafenib, sunitinib, bortezomib, and other similar agents).
9. Patient has any signs of intestinal obstruction.
10. Patient is not able to swallow oral medication.
11. Patients receiving whole brain radiation within 14 days prior to the first dose of study drugs will be excluded. NOTE: Patients receiving palliative radiation (other than whole brain) before or during treatment may still be eligible as long as there are evaluable lesions that are not being irradiated.
12. Pemetrexed arms only: Presence of third space fluid which cannot be controlled by drainage.
13. Additional Exclusions for the 3 pazopanib containing arms (Crizotinib plus Pazopanib) and (Pazopanib plus Pemetrexed) and (Crizotinib plus Pazopanib plus Pemetrexed). 1. History of stroke or transient ischemic attack within 6 months prior to study enrollment. 2. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment. 3. Urine for proteinuria \> or = 2+ (patients discovered to have \> or = 2+ proteinuria on urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate \< or = 1g of protein in 24 hours to be eligible).