Houston, Texas 77030


Purpose:

The goal of this clinical research study is to learn about the safety of giving the combination of pembrolizumab, carboplatin, and paclitaxel to patients with high-grade epithelial non-mucinous ovarian, primary peritoneal, or Fallopian tube cancer. Researchers want to find out how the disease responds to therapy with pembrolizumab. This is an investigational study. Pembrolizumab is FDA-approved and commercially available for the treatment of certain types of melanoma. Its use in patients with ovarian cancer is investigational. Carboplatin and paclitaxel are both FDA-approved and commercially available for the treatment of advanced ovarian cancer. The study doctor can explain how the study drug combination is designed to work. Up to 30 participants will be enrolled in this study. All will take part at MD Anderson.


Study summary:

Treatment: If you are found to be eligible to take part in this study and agree, you will have standard chemotherapy, your scheduled surgery, and then chemotherapy in combination with pembrolizumab. Neoadjuvant Treatment: You will receive standard chemotherapy treatment for three 21-day cycles, or possibly more cycles if the doctor thinks it is in your best interest: - On Day 1 of each cycle, you will receive carboplatin by vein over 1 hour. - On Days 1, 8, and 15 of each cycle, you will receive paclitaxel by vein over 3 hours. Surgery: You will then have your scheduled surgery. Some of the tissue removed during the surgery will be used for immune system testing and to compare to tissue collected before chemotherapy. Adjuvant Treatment and Maintenance: After you have recovered from surgery (about 3-6 weeks later), you will begin receiving chemotherapy again along with the drug pembrolizumab. You will receive the standard chemotherapy in the same way you received it during Cycles 1-3. - On Day 1 of each cycle, you will receive pembrolizumab by vein over 30 minutes during Cycles 4-26. Cycles 7-26 are called the Maintenance Phase. - You will receive carboplatin and paclitaxel during Cycles 4-6 only. Study Visits: On Day 1 of each cycle during Neoadjuvant Treatment: - You will have a physical exam. If the study doctor thinks it is needed, you will also have a pelvic exam. - Blood (about 3 tablespoons) will be collected for routine tests. If you can become pregnant, urine will be collected and/or part of this blood sample will be used for a pregnancy test. - In Cycle 1 only, blood (about 1 tablespoon) will be drawn for biomarker testing. The biomarker tests in this study may include genetic biomarkers. Biomarkers are found in the blood and tissue and may be related to your reaction to the study drug. Study Visits during Neoadjuvant Therapy: On Days 1, 8 and 15 of each cycle during Neoadjuvant Treatment, blood (about 1-2 tablespoons) will be drawn for routine tests. At your visit before the surgery: - You will have a physical exam. - Blood (about 3 tablespoons) will be drawn for routine and biomarker testing. - You will have a CT scan or MRI to check the status of the disease. You will sign a separate consent form for the surgery that explains the procedure and its risks. During the surgery, tumor tissue will be collected for biomarker and genetic testing. All samples will be stored at MD Anderson for an unlimited amount of time for testing related to this study. On the day of surgery, blood (about 3 tablespoons) will be drawn for routine testing. At your postoperative visit (visit after surgery): - You will have a physical exam. - Blood (about 3 tablespoons) will be drawn for routine testing. Study Visits during Adjuvant Therapy: On Day 1 of each cycle during Adjuvant Treatment: - You will have a physical exam. - Blood (about 3 tablespoons) will be drawn for routine and biomarker testing. - Urine will be collected for routine testing. If you can become pregnant, part of this urine and/or blood sample will be used for a pregnancy test. On Days 8 and 15 of each cycle during Adjuvant Treatment, blood (about 1-2 tablespoons) will be drawn for routine tests. Study Visits during Maintenance Therapy: - You will have a physical exam. - Blood (about 3 tablespoons) and urine will be collected for routine tests. Every 12 weeks, you will have a CT scan or MRI to check the status of the disease. Length of Study: You will the receive study drug(s) for up to 23 cycles, or possibly more if the doctor thinks it is appropriate for you to have more than 3 Neoadjuvant Treatment cycles. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. After you are no longer taking any study drugs, the study staff will continue to call you every 3 months to check the status of your health. Post-Treatment Visits: After the last dose of study drug(s), the following tests and procedures will be performed: - You will have a physical exam. - You will have a CT or MRI to check the status of the disease. - Blood (about 1-2 tablespoons) will be drawn for routine tests. About 30 days after the last dose of study drugs, you will have a physical exam.


Criteria:

Inclusion Criteria: 1. Signed, written Informed Consent 2. Women 18 years of age or older. 3. Histology showing high-grade epithelial non-mucinous ovarian, primary peritoneal, or fallopian tube cancer 4. No more than 4 prior cycles of chemotherapy for primary advanced (Stage III or IV) epithelial ovarian, primary peritoneal, or fallopian tube cancer. 5. No prior treatment involving irradiation, hormonal therapy, immunotherapy, investigational therapy, and/or other concurrent agents or therapies for ovarian cancer. 6. A disposition to neoadjuvant chemotherapy with planned interval tumor reductive surgery after 4 complete cycles of treatment 7. Planned dose-dense chemotherapy with combination carboplatin and paclitaxel given intravenously 8. Have measurable disease based on RECIST 1.1. a. Measurable disease is defined at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each "target" lesion must be >/=20 mm when measured by conventional techniques, including palpation, plain x-ray, CT, and MRI, or >/=10 mm when measured by spiral CT. b.Patients with non-measurable but evaluable solid tumors may be deemed eligible contingent upon PI review. 9. Peripheral neuropathy Grade 0 or 1 by NCI CTCAE version 4.0 10. Tissue from an archival tissue sample or fresh tissue obtained from a core or excisional biopsy of a tumor lesion. 11. Have a performance status of 0 or 1 on the ECOG Performance Scale. 12. Adequate organ function as determined by the following laboratory values: a. ANC >/=1,500 /mcL b. Platelets >/=100,000 / mcL c. Hgb >/=9 g/dL or >/=5.6 mmol/L d. Creatinine Clearance >/=60 mL/min for subject with creatinine levels > 1.5 X institutional ULN e. Total Bilirubin </= 1.5 X ULN OR Direct bilirubin </= ULN for subjects with total bilirubin levels > 1.5 ULN f. AST (SGOT) and ALT (SGPT) </= 2.5 X ULN OR </= 5 X ULN for subjects with liver metastases g. INR/PT </=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) h. PTT </=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 13. Women of child-bearing potential (intact uterus) should have a negative urine or serum pregnancy within 72 hours prior to receiving the first 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. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 14. 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 (Reference Section 6.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 15. Pre-treatment fresh frozen tissue available for research purposes. This tissue can be collected from preoperative laparoscopy, other diagnostic biopsy, or a research-specific biopsy. 16. Signed informed consent on protocol LAB02-188. Exclusion Criteria: 1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment. 2. Histology showing mucinous or low grade epithelial ovarian carcinoma 3. History of another primary malignancy except for: • Malignancy treated with curative intent and with no known active disease >/=5 years before the first dose of study drug and or low potential risk for recurrence • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease • Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ 4. 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 Study 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 treatment. 5. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). 6. Patients with ovarian cancer not medically fit for diagnostic laparoscopy prior to initiation of therapy 7. Patients with any evidence of severe or uncontrolled systemic disease (e.g. severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease], uncontrolled chronic renal disease [glomerulonephritis, nephritic syndrome, Fanconi Syndrome or Renal tubular acidosis]), or current unstable or uncompensated respiratory or cardiac conditions, or uncontrolled hypertension blood pressure >/= 140/90, active bleeding diatheses or active infection. 8. 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 study treatment. 9. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., </= Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 10. 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., </= Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: Subjects with </= Grade 2 neuropathy are an exception to this criterion and may qualify 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. 11. No active autoimmune disease that has required systemic treatment in past two years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). 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. 12. Has evidence of interstitial lung disease or active, non-infectious pneumonitis. 13. Has an active infection requiring systemic therapy. 14. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 15. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study. 16. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment. 17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). 19. Has received a live vaccine within 30 days prior to the first dose of study treatment. 20. Patients with tuberculosis. 21. Patients with known hypersensitivity to pembrolizumab or any of its excipients 22. Patients receiving concurrent additional biologic therapy 23. History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin, paclitaxel not responsive to traditional desensitization procedures. 24. Patient that is not able to understand or to comply with the study instructions and requirements or has a history of non-compliance to the medical regimen.


NCT ID:

NCT02520154


Primary Contact:

Principal Investigator
Robert Coleman, MD
M.D. Anderson Cancer Center

Robert Coleman, MD
Phone: 713-745-3357


Backup Contact:

N/A


Location Contact:

Houston, Texas 77030
United States



There is no listed contact information for this specific location.

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 22, 2017

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