Study of Brentuximab Vedotin And Bevacizumab In Refractory CD-30 Positive Germ Cell Tumors

Inclusion Criteria:

* Male, ≥ 18 years of age
* Diagnosis of CD-30 positive germ cell tumor. CD30 expression will be tested by immunohistochemistry (IHC) in archival or fresh tumor tissue as is routinely done for diagnosis.
* Disease progression on imaging or tumor marker progression (clinical significance of tumor marker progression to be decided per the discretion of treating physician) after at least 2 lines of platinum-based chemotherapies unless patient is ineligible for further platinum based chemotherapy or refuses 2nd line platinum based chemotherapy due to toxicity. For primary mediastinal germ cell tumors, failure of first-line chemotherapy will be accepted. Prior high dose chemotherapy with hematopoietic stem cell rescue is allowed. Prior treatment with bevacizumab is allowed.
* At least 3 weeks should have elapsed since the last treatment (e.g. chemotherapy, targeted small molecule therapy, immunotherapy or radiation) and must have recovered to grade 1 or better from the acute effects of prior therapy.
* Presence of measurable disease according to RECIST 1.1
* ECOG performance status 0 or 1
* Adequate marrow and organ function within 28 days prior to study registration as defined below:

  * Leukocytes \> 3,000/µL
  * ANC \> 1500/µL
  * Hemoglobin ≥ 9 g/dL, Note: Blood transfusion will be allowed for patients with hemoglobin \< 9 g/dl and G-CSF is allowed for neutropenic patients at time of enrollment.
  * Platelets \> 100,000/mm3
  * Creatinine: ≤3mg/dl OR if serum creatinine \> 3 mg/dl, estimated GFR \>30 mL/min/1.73m2
  * INR: \<1.5 x institutional upper limit of normal OR \< 3 if on warfarin or other anticoagulants. There should be no evidence of active bleeding while on anticoagulants.
  * Total bilirubin: ≤ 2 x institutional upper limit of normal (ULN)
  * SGOT (AST) or SGPT (ALT): \< 3 x institutional upper limit of normal (\< 5 x ULN if liver metastases present)
  * Proteinuria: If patient has proteinuria, it should be \<2+ (\< 100 mg/dl or per institutional guidelines). If proteinuria is 2+ or greater (≥ 100 mg/dl per institutional guidelines), patients should undergo a 24- hour urine collection and 24 hour urinary protein should be less than \< 2 grams.
* Sexually active men with partners of women of childbearing potential must agree to practice effective methods of contraception during the study and for 6 months after the last treatment
* Provide voluntary written consent and HIPAA authorization for release of personal health information, approved by an Institutional Review Board/Independent Ethics Committee (IRB/IEC)

Exclusion Criteria:

* Prior treatment with Brentuximab Vedotin.
* Known active brain metastases and or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided brain metastases are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study registration. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
* History of blood clots, pulmonary embolism, or deep vein thrombosis in previous 6 months unless controlled by anticoagulant treatment
* Known history of HIV
* Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected)
* Received a live vaccine within 1 week prior to the first dose of study treatment
* Has active autoimmune disease that required systemic treatment with use of disease modifying agents, corticosteroids or immunosuppressive drugs
* Any clinically significant active infection that requires systemic treatment at the time of enrollment.
* Known allergy to bevacizumab or brentuximab vedotin or any of its excipients
* Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction (MI) within 6 months of study registration
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess in previous 6 months
* Prior major surgery within the previous 28 days of study registration and/or presence of any non-healing wound, fracture, or ulcer.
* Use of an investigational agent within the previous 28 days of study registration.
* Poorly controlled hypertension \[defined as systolic blood pressure (SBP) of ≥150 mmHg and/or diastolic blood pressure (DBP) of ≥ 90mmHg\]. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study registration
* Arterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, or MI within 6 months of study registration
* History of posterior reversible encephalopathy syndrome
* Other malignancies unless the patient is considered to be disease-free and has completed therapy for the malignancy \> than 6 months prior to study entry
* Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
* Concurrent use of rifampin or ketoconazole