Patient case: 61-year-old male with Ampullary carcinoma. Genetic variant: KRAS. Other conditions: None.

Clinical trial: Study for the Evaluation of Efficacy of Pembrolizumab (MK-3475) in Patients With Rare Tumors

Summary: The goal of this clinical research study is to learn if pembrolizumab (also called MK-3475) can help control the disease in patients with advanced cancer.

Detailed description: Study Groups:
  If you are found to be eligible to take part in this study, you will be assigned to a study group based on your disease type. There will be 10 groups enrolled on this study for the 10 different disease types being tested. Up to 25 participants will be enrolled in each of the 10 disease groups.
  Study Drug Administration:
  You will receive pembrolizumab by vein over 30 minutes on Day 1 of each 21-day study cycle. The time between doses may increase if you have side effects.
  Study Visits:
  On Day 1 of Cycle 1:
  -  You will have a physical exam.
  -  Blood (about 3 teaspoons) will be drawn for routine tests.
  -  If you can become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test.
  Every week until Week 9, every 2 weeks between Weeks 9 and 54, and then every 4 weeks after that until Week 81 or your treatment ends, whichever comes first, you will complete a questionnaire about your health and how you are feeling. This questionnaire will be either emailed to you or you will receive a phone call and an automated voice system will ask you these questions.
  Between Days 15-21 of Cycle 1:
  -  If the doctor thinks it is possible, you will have a tumor biopsy performed for PD testing.
  -  Blood (about 2 teaspoons) will be drawn for PD testing.
  On Day 1 of Cycles 2 and 3:
  -  You will have a physical exam.
  -  Blood (about 3 teaspoons) will be drawn for routine tests.
  -  If you can become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test.
  Every 9 weeks:
  -  You will have a CT scan, MRI, or bone scan to check the status of the disease.
  -  If the doctor thinks it is needed, blood (about 1 teaspoon) will be drawn for tumor marker testing.
  -  Blood (about 2 teaspoons) will be drawn for PD testing.
  On Day 1 of Cycles 4 and beyond:
  -  You will have a physical exam.
  -  Blood (about 3 teaspoons) will be drawn for routine tests.
  -  Blood (about 3 teaspoons) will be drawn to check how well your blood clots and to check your thyroid function (every 3 cycles only).
  -  Urine will be collected for routine tests (every 3 cycles only).
  -  If you can become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test.
  If your doctor thinks it is needed, these tests may be performed more often.
  Stopping Pembrolizumab:
  If the cancer has not gotten worse after 24 months on study, you will stop taking study therapy. You will complete a safety follow-up visit and then your disease status will be monitored every 8 weeks by imaging scans. If at any point during this time the cancer gets worse, you may be eligible to receive an additional 12 months of treatment with pembrolizumab during the Second Course. When you stop taking the study drug you will be asked to come in for a safety follow-up visit about 30 days later or before you start a new treatment for the cancer, whichever comes first.
  Second Course Treatment:
  If you stop taking the study drug because the disease goes away, and the disease comes back later, you may be able to start taking the study drug again. This will be known as "Second Course Treatment".
  Depending on your tumor type, tumor marker data will also be collected for this study.
  Repeated Tests If The Disease Gets Worse:
  If the imaging scans shows that the cancer may have worsened, you may be asked to have another imaging scan at least 4 weeks later to confirm. The study doctor will discuss your options during the period between scans, which may include the following:
  -  Continue to receive treatment with the study drug or;
  -  Have study drug held until the time of the follow-up scan or;
  -  Discontinue from the study and instead receive an FDA approved drug.
  You may be eligible to receive treatment with a different investigational drug.
  If you decide to stay in the study until the confirmation scan, you will not be eligible to receive any of these other drugs until the worsening of the disease is confirmed.
  Length of Study:
  You may continue taking the study drug for up to 24 months, as long as the doctor thinks it is in your best interest. If the disease gets worse after you have completed 24 months of treatment and stopped treatment, you may continue taking the drug for up to 12 months if your doctor thinks it is best. You will no longer be able to take the study drug if intolerable side effects occur, or if you are unable to follow study directions.
  End of Treatment Visit:
  After your last dose of study drug, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:
  -  You will have a physical exam.
  -  Blood (about 3 teaspoons) will be drawn for routine tests.
  -  Blood (about 2 teaspoons) will be drawn for PD testing.
  -  You will have a CT scan, MRI, or bone scan to check the status of the disease.
  -  If the doctor thinks it is needed, blood (about 1 teaspoon) will be drawn for tumor marker testing.
  -  If you can become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test.
  -  If the doctor thinks it is possible, you will have a tumor biopsy performed for PD testing.
  -  If this visit happens before Week 81, you will complete a questionnaire about your health and how you are feeling.
  Follow-Up Visit:
  Within 30 days after your last pembrolizumab dose:
  -  You will have a physical exam.
  -  Blood (about 6 teaspoons) will be drawn for routine tests, to check how well your blood clots, and thyroid function tests.
  -  Urine will be collected for routine tests.
  Every 9 weeks after your last pembrolizumab dose:
  -  You will have a physical exam.
  -  Blood (about 3 teaspoons) will be drawn for routine tests.
  -  You will have a CT scan, MRI, or bone scan to check the status of the disease.
  -  If the doctor thinks it is needed, blood (about 1 teaspoon) will be drawn for tumor marker testing.
  Every 12 weeks after your last dose of pembrolizumab, you will be contacted by phone to ask how you are doing. The call should take about 15-20 minutes.
  This is an investigational study. Pembrolizumab is FDA approved for the treatment of certain types of melanoma and non-small cell lung cancer, however it has not been approved for advanced cancer. In this study it is being used for research purposes only. The study doctor can explain how the study drug is designed to work.
  Up to 250 participants will be enrolled in this study. All will take part at MD Anderson.

Eligibility: Inclusion Criteria:
  1. Be willing and able to provide written informed consent/assent for the trial.
  2. Be >/= 18 years of age on day of signing informed consent.
  3. Have measurable disease based on RECIST 1.1 or evaluable disease (non-measureable lesions). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Patients may have bone metastatic disease evaluable according to tumor evaluation criteria best suitable and accepted for the tumor type evaluated.
  4. Have one of the following advanced (unresectable and/or metastatic) solid tumor indications, that has progressed following standard therapies, where standard therapies are available: 1) Squamous cell carcinoma of the skin 2) Anaplastic thyroid cancer 3) Adrenocortical carcinoma 4) Medullary renal cell carcinoma 5) Carcinoma of unknown primary 6) Penile carcinoma 7) Thymoma 8) Germ Cell Tumor 9) Paraganglioma-pheochromocytoma 10) Other rare tumors (except those tumor types listed in Exclusion #19/20)
  5. Have failed prior treatment within 6 months of consent date.
  6. Have biopsiable disease. Subjects must have at least one lesion amenable to biopsy. Tumor lesions used for biopsy should not be lesions used as RECIST target lesions. In Cohort 9: Paraganglioma-pheochromocytoma or Cohort 10, where there is prominent bony disease, biopsies may not be possible due to the nature of the disease.
  7. Be willing to provide archival tissue. If archival tissue is not available, a newly obtained core or excisional biopsy of a tumor lesion will be obtained. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. In Cohort 9: Paraganglioma-pheochromocytoma or Cohort 10, where there is prominent bony disease, biopsies may not be possible due to the nature of the disease.
  8. Have a performance status of 0 or 1 on the ECOG Performance Scale.
  9. Demonstrate adequate organ function, all screening labs should be performed within 28 days of treatment initiation. Hematological: Absolute neutrophil count (ANC) >/=1,000/mcL; Platelets >/=75,000/mcL, Hemoglobin >/=9 g/dL or >/=5.6mmol/L without transfusion or EPO dependency (within 7 days of assessment). Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) </=1.5X upper limit of normal (ULN) OR >/=60 mL/min for subject with creatinine levels > 1.5X institutional ULN.
  10. CONTINUED FROM #8: Hepatic: Serum total bilirubin </=1.5X ULN OR Direct bilirubin </= ULN for subjects with total bilirubin levels > 1.5 ULN, AST (SGOT) and ALT (SGPT) </=2.5X ULN OR </=5X ULN for subjects with liver metastases, Albumin >2.5 mg/dL. Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) </=1.5X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants, Activated Partial Thromboplastin Time (aPTT) </=1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  11. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  12. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  13. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  Exclusion Criteria:
  1. Is currently participating and receiving study therapy at the time of administration of first dose of trial treatment
  2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  3. Has a known history of active TB (Bacillus Tuberculosis).
  4. Hypersensitivity to pembrolizumab or any of its excipients.
  5. Has not recovered (i.e., </= Grade 1 or at baseline) from adverse events due to a previously administered agent. a. Note: Subjects with </= Grade 2 neuropathy are an exception to this criterion and may qualify for the study. b. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  6. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, and diseases for which the treatment could reasonably include Pembrolizumab and are not part of the excluded tumor type list or not eligible for the phase I trial.
  7. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they 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 trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  8. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of Pembrolizumab. Note: corticosteroids given within 24 hours of an imaging study for purposes of pre-medication in patients with hypersensitivity to radiologic contrast agents are allowed.
  9. Has known history of, or any evidence of active, non-infectious pneumonitis.
  10. Has an active infection requiring systemic therapy.
  11. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  13. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  14. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  17. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  18. Is participating in Cohort 10 and has melanoma; non-small cell lung cancer; hepatocellular carcinoma; Merkel cell carcinoma; colon or rectal adenocarcinoma; anal canal squamous cell carcinoma; pancreas adenocarcinoma; esophageal squamous cell carcinoma or adenocarcinoma (including GE junction); biliary tract adenocarcinoma (gallbladder and biliary tree but excluding ampulla of vater cancers); carcinoid tumors; neuroendocrine carcinomas (well or moderately differentiated pancreatic neuroendocrine tumor); ER-positive HER2-negative breast cancer; triple negative breast cancer; ovarian epithelial, fallopian tube or primary peritoneal carcinoma; endometrial carcinoma; cervical squamous cell cancer; vulvar squamous cell carcinoma; small cell lung cancer; mesothelioma (malignant pleural mesothelioma); thyroid cancer (papillary or follicular subtype); salivary gland carcinoma; nasopharyngeal carcinoma; glioblastoma multiforme; leiomyosarcoma;
  19. CONTINUED FROM #18: prostate adenocarcinoma; gastric adenocarcinoma; or small bowel malignancy.

Relevance to patient case: not relevant