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

• Status: Recruiting
• Trial end date: 0000-00-00
• Target enrollment: 250
• Participant gender: Both

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Pembrolizumab
• Last Updated: 2016-12-12

Criteria

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. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

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) Testicular carcinoma 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.

7. Be willing to provide archival tissue. If archival tissue is not available, or 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.

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)/=60 mL/min for subject with creatinine levels > 1.5X institutional ULN.

10. CONTINUED FROM #8: Hepatic: Serum total bilirubinULN for subjects with total bilirubin levels > 1.5 ULN, AST (SGOT) and ALT (SGPT) 2.5 mg/dL. Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT)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)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 or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of 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 had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e.,due to agents administered more than 4 weeks earlier.

6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e.,baseline) from adverse events due to a previously administered agent. - Note: Subjects withqualify for the study. - Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

7. 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.

8. 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.

9. 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.

10. Has known history of, or any evidence of active, non-infectious pneumonitis.

11. Has an active infection requiring systemic therapy.

12. 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.

13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

14. 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.

15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

18. 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.

19. 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;

20. CONTINUED FROM #19: prostate adenocarcinoma; gastric adenocarcinoma; or small bowel malignancy.