DART – Dual Anti-CTLA-4 and Anti-PD-1 Blockage in Rare Tumors.


Research & Trial Information

Protocol#: SWOG – S1609 – DART

Cancer Type: Genomic Based Trial

Eligibility:

  1. Patients must have histologically confirmed rare cancer identified, that did not have a match to a molecularly-guided therapy on EAY131 “NCIMATCH” protocol or who progressed on molecularly-matched therapy and have no further molecularly-matched treatment recommendations per EAY131, “NCIMATCH”.
  2. Patients who meet criteria in and are determined to have a rare cancer with unknown primary site are eligible under Cohort #32 (Tumor of unknown primary (Cancer of Unknown Primary; CuP), provided that there is histologic documentation of metastatic malignancy with no discernible primary site identified from histopathologic review, physical exam and associated crosssectional imaging of the chest, abdomen, and pelvis.
  3. Patients must have progressed following at least one line of standard systemic therapy and there must not be other approved/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls). Patients who cannot receive other standard therapy that has been shown to prolonged survival due to medical issues will be eligible, if other eligibility criteria are met. OR Patients for whose disease no standard treatment exists that has been shown to prolong overall survival.
  4. Patients must have a diagnostic quality CT scan or MRI, performed within 28 days prior to registration, which demonstrates measurable disease.
    • Adequately managed Stage I or II cancer from which the patient is No other prior malignancy is allowed except for the following:currently in complete remission
    • Any other cancer from which the patient has been disease free for one year.
    • Adequately managed Stage I or II follicular thyroid or prostate cancer is also eligible, wherein patient is not required to be in complete remission.
  5. Patients may have received either prior anti-CTLA4 or other prior anti-PD-1/anti- PD-L1 therapy, not both, provided that it is completed ≥ 4 weeks prior to registration for monoclonal therapy, ≥ 8 weeks prior to registration if therapy involved immune-stimulatory mAbs, and ≥ 28 days for all other immunotherapy.
  6. Patients who had prior immune-related adverse event (Grade 3 or higher immunerelated pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy (e.g. cancer vaccine, cytokine, etc.) are not eligible.
  7. Patients with clinically controlled thyroiditis or pituitary disorders on stable replacement therapy are eligible.
  8. Patients are not eligible if they have had or are planned for solid organ transplant. Patients who have received allogeneic hematopoietic stem cell transplant areeligible if:
    1. The transplant occurred at least 90 days prior to registration,
    2. Patient has no prior acute graft versus host disease (GVHD), and
    3. Within 48 hours of registration, patient demonstrates at least 90%

    engraftment, defined as: ANC ≥ 500 mcl, measured over 3 consecutive

    days or 1 day with an ANC ≥ 1,000 mcl, or platelets ≥ 50,000 mcl

    measured, wherein the patient did not receive any platelet transfusions within 7 days prior to laboratory assessment.

  9. Patients with autoimmune disease who are otherwise eligible under criterion 5.3l must not have received steroid and immunosuppressive therapy within 28 days prior to registration.
  10. Patients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy ≥ 28 days prior to registration and have stable disease at time of registration. Metastatic brain parenchymal disease must have been treated and patient must be off steroids for 7 days prior to registration. Patients must have a CT or MRI scan of the brain to evaluate for CNS disease within 42 days prior to registration.
  11. Patients must not currently be receiving any other investigational agents or any other systemic anti-cancer therapy (including radiation). In event patient, recently received any other systemic anti-cancer therapy, patient must be off therapy at least 7 days prior to registration and any therapy-induced toxicity must have recovered to ≤ Grade 1.
  12. Patients must not have prior history of allergy or known hypersensitivity to nivolumab or ipilimumab.
  13. Patients must be ≥ 18 years of age.
  14. Patients must have a Zubrod Performance Status of 0-2.
  15. Patients must not have known active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection at time of registration. Patients with previously treated HBV or HCV that have an undetectable viral load and no residual hepatic impairment are eligible.
  16. Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, immunosuppressive drugs, or corticosteroids with doses higher than prednisone 10mg or equivalent). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Autoimmune diseases include but are not limited to autoimmune hepatitis, inflammatory bowel disease (including ulcerative colitis and Crohn’s disease), as well as symptomatic disease (e.g.: rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener’s Granulomatosis]); CNS or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and Myasthenia Gravis, multiple sclerosis or glomerulonephritis). Vitiligo, alopecia, hypothyroidism on stable doses of thyroid replacement therapy, psoriasis not requiring systemic therapy within the past 3 years is permitted. Short-term steroid premedication for contrast allergy is permitted.
  17. Patients must not have any uncontrolled intercurrent illness including (not limited to): Symptomatic CHF (NYHA III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks prior to registration, Unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI CTCAE v4 Grade ≥ 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (≥ Grade 3).Note: Patients with history of CHF or patients who are deemed at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs should have an EKG and ECHO, as clinically indicated, at baseline and at the start of each cycle. Patients who have evidence at baseline (or subsequently) of CHF, MI, cardiomyopathy, or myositis cardiac evaluation (NYHA I/II) should have additional consult by a cardiologist, including review of EKG, CPK, troponin, echocardiogram, as clinically indicated.
  18. Patients must not have symptomatic interstitial lung disease or pneumonitis.
  19. Patients must have fully recovered from any adverse effects of major surgery (to ≤ Grade 1).