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Trial record 10 of 2318 for:    melanoma

Study of Oral Azacitidine (CC-486) in Combination With Pembrolizumab (MK-3475) in Patients With Metastatic Melanoma

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ClinicalTrials.gov Identifier: NCT02816021
Recruitment Status : Recruiting
First Posted : June 28, 2016
Last Update Posted : October 3, 2017
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
Brief Summary:

Participant is being asked to take part in this study because participant has advanced melanoma.

The goal of this clinical research study is to learn if oral azacitidine (CC-486) and pembrolizumab (MK-3475) can help to control melanoma. The safety of this drug combination will also be studied.

This is an investigational study. Azacitidine is FDA approved and commercially available for the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia. Pembrolizumab is FDA approved and commercially available for the treatment of melanoma. It is considered investigational to use this drug combination to treat melanoma.

The study doctor will explain how the study drugs are designed to work.

Up to 71 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Melanoma and Other Malignant Neoplasms of Skin Metastatic Melanoma Drug: Azacitidine Drug: Pembrolizumab Phase 2

  Show Detailed Description

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 71 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Oral Azacitidine (CC-486) in Combination With Pembrolizumab (MK-3475) in Patients With Metastatic Melanoma
Actual Study Start Date : February 14, 2017
Estimated Primary Completion Date : February 2025
Estimated Study Completion Date : February 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Arm A: Metastatic Melanoma - PD-1 Naive

Thirty-six participants with metastatic melanoma that are PD-1 naïve enrolled in treatment Arm A.

Treatment consists of 3-week cycles and continues until disease progression. Oral Azacitidine administered by mouth daily for 15 days (Days 1-15) of every cycle. Pembrolizumab administered by vein every 3 weeks and after the oral dose of Azacitidine on concurrent treatment days.

Drug: Azacitidine
300 mg by mouth daily for 15 days (Days 1-15) of every cycle.
Other Names:
  • 5-azacytidine
  • 5-aza
  • Vidaza
  • 5-AZC
  • Ladakamycin
  • NSC-102816
  • Azacytidine
Drug: Pembrolizumab
200 mg by vein every 3 weeks and after the oral dose of Azacitidine on concurrent treatment days.
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475
Experimental: Arm B: Metastatic Melanoma - Post PD-1 Progression

Thirty-five participants with metastatic melanoma that have progressed on PD-1 directed therapy enrolled in treatment Arm B.

Treatment consists of 3-week cycles and continues until disease progression. Oral Azacitidine administered by mouth daily for 15 days (Days 1-15) of every cycle. Pembrolizumab administered by vein every 3 weeks and after the oral dose of Azacitidine on concurrent treatment days.

Drug: Azacitidine
300 mg by mouth daily for 15 days (Days 1-15) of every cycle.
Other Names:
  • 5-azacytidine
  • 5-aza
  • Vidaza
  • 5-AZC
  • Ladakamycin
  • NSC-102816
  • Azacytidine
Drug: Pembrolizumab
200 mg by vein every 3 weeks and after the oral dose of Azacitidine on concurrent treatment days.
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475


Outcome Measures

Primary Outcome Measures :
  1. Objective Response Rate in Participants with Metastatic Melanoma That Are PD-1 Naïve (Arm A) or That Have Progressed on PD-1 Directed Therapy (Arm B) [ Time Frame: After 4 cycles. Each cycle is 21 days. ]
    Objective Response Rate determined by Response Evaluation Criteria In Solid Tumors (RECIST 1.1).

  2. Objective Response Rate in Participants with Metastatic Melanoma That Are PD-1 Naïve (Arm A) or That Have Progressed on PD-1 Directed Therapy (Arm B) [ Time Frame: After 4 cycles. Each cycle is 21 days. ]
    Objective response rate determined by Immune Related Response Criteria (ir-RC).


Secondary Outcome Measures :
  1. Overall Survival in Participants with Metastatic Melanoma That Are PD-1 Naïve (Arm A) or That Have Progressed on PD-1 Directed Therapy (Arm B) [ Time Frame: 1 year ]
    Overall survival defined as the interval between time of enrollment and the date of death from any cause. Overall survival analyzed using the Kaplan-Meier method.

  2. Progression Free Survival in Participants with Metastatic Melanoma That Are PD-1 Naïve (Arm A) or That Have Progressed on PD-1 Directed Therapy (Arm B) [ Time Frame: After 6 cycles. Each cycle is 21 days. ]
    Progression free survival defined as the time between the date of enrollment and the date of either disease progression or date of death, whichever is earlier. Progression free survival summarized and plotted using Kaplan-Meier method.


Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients who have unresectable Stage III through stage IV metastatic melanoma that have not received prior PD-1 directed therapy (Arm A) or that have progressed despite prior PD-1 directed therapy (Arm B).
  2. Be willing and able to provide written informed consent/assent for the trial.
  3. Be >/= 18 years of age on day of signing informed consent.
  4. Have measurable or evaluable disease based on RECIST 1.1.
  5. Be willing to provide archival or fresh tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 4 weeks (28 days) prior to initiation of treatment on Day 1. Subjects from whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Principal Investigator.
  6. Have a performance status of 0 or 1 on the ECOG Performance Scale.
  7. Demonstrate adequate organ function, all screening labs should be performed within 14 days of treatment initiation. Hematological: Absolute neutrophil count (ANC) >/= 1,500 /mcL; Platelets >/= 100,000 / mcL; Hemoglobin >/= 9 g/dL or >/= 5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment). Renal: Serum creatinine </= 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance >/= 60mL/min for subjects with creatinine levels > 1.5 X ULN. Hepatic: Serum total bilirubin </= 1.5 X ULN or direct bilirubin </= ULN for subjects with total bilirubin levels > 1.5 ULN; AST (SGOT) and ALT (SGPT) 9 </= 2.5 X ULN OR </= 5 X ULN for subjects with liver metastases.
  8. contd from #7. Albumin >/= 2.5 g/dL. Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) 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 </= 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
  9. 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.
  10. 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.
  11. 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, azacitidine, mannitol, or any of their 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., </= Grade 1 or at baseline) from adverse events 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., </= 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.
  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.
  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.
  10. Has known history of, or any evidence of active, non-infectious pneumonitis.
  11. Significant active cardiac disease within the previous 6 months including: - NYHA class 4 CHF - Unstable angina - Myocardial infarction
  12. Has an active infection requiring systemic therapy.
  13. 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.
  14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  15. 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.
  16. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent [for Arm A only].
  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 of planned start of study therapy.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02816021


Contacts
Contact: Hussein Tawbi, MD, PHD 713-792-2921 CR_Study_Registration@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77330
Contact: Clinical Research Operations       CR_Study_Registration@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Merck Sharp & Dohme Corp.
Celgene
Investigators
Principal Investigator: Hussein Tawbi, MD, PHD M.D. Anderson Cancer Center
More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02816021     History of Changes
Other Study ID Numbers: 2016-0069
NCI-2016-01185 ( Other Identifier: NCI CTRP )
First Posted: June 28, 2016    Key Record Dates
Last Update Posted: October 3, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Melanoma and other malignant neoplasms of skin
Metastatic melanoma
Advanced melanoma
Azacitidine
5-azacytidine
5-aza
Vidaza
5-AZC
Ladakamycin
NSC-102816
Azacytidine
Pembrolizumab
Keytruda
MK-3475
SCH-900475

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Neoplasms
Skin Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms by Site
Skin Diseases
Pembrolizumab
Azacitidine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors