*Credentialing required. Please check your site's credentialing status.

CURRENT SITES CREDENTIALED:
 St. Alphonsus, SJMO, SJMH, St. John Hosp., Sparrow, Macomb, Saginaw, Lehigh Valley

-There are two patient populations eligible for the study:
--Patients who have not started any therapy with LHRH agonist or antagonist (Early Induction Group)
--Patients who have already started therapy with LHRH agonist or antagonist within the 30 days prior to registration (Late Induction Group).
-Patients must be registered within 30 days of first injection of the LHRH agonist or antagonist.
-All patients must have a histologically or cytologically proven diagnosis of adenocarcinoma of the prostate.
-All patients must have distant metastatic disease as evidenced by soft tissue and/or bony metastases prior to initiation of androgen deprivation therapy.
-Patients with known brain metastases are not eligible.
-Patients who are deemed to have high-risk or extensive metastatic, hormone sensitive prostate cancer per "clinical judgment" of the treating physician are eligible for enrollment if they are unsuitable candidates for docetaxel or if they have declined docetaxel therapy.
-Patients may have received prior androgen deprivation therapy- neoadjuvant and/or adjuvant setting only-but it must not have lasted for more than 36 months. Single or combination therapy allowed. At least 6 months must have elapsed since completion of the therapy and serum testosterone must be greater than 50ng/mL (non-castrate levels) for early induction patients.
-Patients must not have received prior and/or must not have any plans for receiving concomitant therapy with ketoconazole, aminoglutethimide or abiraterone acetate, or enzalutamide (MDV3100). Concurrent megestrol for hot flashes is allowed.
-Patients must not have received any prior cytotoxic chemotherapy for metastatic prostate cancer. Prior cytotoxic chemotherapy with curative intent in the neoadjuvant/adjuvant setting is allowed, but at least 2 years must have elapsed since completion.
-Patients may have received prior surgery.
-Patients may have received or plan to receive concurrent bone targeting agents that do not have an effect on PSA.
-For the late induction group, patients must have had no more than 30d of prior castration for their disease prior to registration. If the patient was on an antiandrogen, the patient must be willing to switch over to bicalutamide or TAK-700. If the method of castration was LHRH antagonists, the patient must be willing to switch to an LHRH agonist.
-Patients must have a PSA greater than or equal to 2 ng/mL.
-Zubrod PS must be 0-2; PS of 3 will be allowed if from bone pain only. 

-Patients must not have received previous systemic anthracycline (intravesical anthracycline is allowed).
-Patients must not have peripheral neuropathy greater than or equal to Grade 2.
-Patients must have tumor tissue from transurethral resection of the bladder tumor

(TURBT) available for submission that is sufficient for COXEN testing.The diagnostic TURBT sample must have been obtained within 56 days prior to

registration.

Screening Eligibility:
-Patients must have pathologically proven squamous cell carcinoma of the lung
-Disease must be stage IV or recurrent. Mixed histologies are not allowed.
-Patients can be screened at progression on prior treatment (at least one line previous was platinum based; must have progressed after most recent line; if received platinum-based for stage I-III, PD must have occurred within a year of that therapy) OR
-Patients can be pre-screened prior to progression on first-line treatment (must have had at least 1 dose of a first-line platinum-based chemotherapy regimen for stage IV)
-Patients must not have received docetaxel for Stage IV disease
-Patients must have adequate tumor tissue available and agree to have this tissue submitted for  profiling and C-MET IHC.
-Patients must not have a known EGFR mutation or ALK fusion.
-Patients must have Zubrod performance status 0- 1
-Pts must be willing to provide prior smoking hx.

Sub-study Eligibility (common criteria for all sub-studies):
-Patients whose biomarker profiling results indicate the presence of EGFR mutation or EML4/ALK fusion are NOT eligible.
-Patients must not have received RT within 28d of registration
-Patients must not have received any prior systemic chemotherapy or IND within 21d prior to registration
-Patients must have measurable disease
-Patients must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 28 days following treatment, AND (2) pt has no residual neurological dysfunction and has been off corticosteroids for at least 14 days prior to randomization.

See substudies for individual substudy additional eligibility criteria.

Substudy B eligibility:
-Patients must be assigned to this substudy- PI3K+
-Patients must not have Type 1 or 2 diabetes which requires anti-hyperglycemic medication
-Patients must not have active or a history of small or large intestine inflammation such as Crohn's disease or ulcerative colitis
-Patients must not require daily supplemental oxygen

-Patients must be assigned to this substudy defined Cell Cycle Gene Alteration Positive
-Patients must not be taking within 7 days prior to sub-study treatment arm randomization, nor plan to take while on protocol treatment drugs that are known to prolong the QT interval
-Patients must not have QTc > 480msec, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes
-Patient may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of palbociclib (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)

-Patients must be assigned to this substudy, defined FGFR positive
-Patients must be greater than or equal to 25 years of age (skeleton maturation is complete)
-Patients must not have had any prior exposure to any agent with FGFR inhibition as its primary pharmacology
-Patients must not have a mean resting corrected QT interval (QTc) > 450 msec obtained from 3 consecutive electrocardiograms (ECGs); any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block); nor any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age
-Patients must not be planning to receive any concomitant medication known to prolong the QT interval