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Pharmacodynamic Study of Pembrolizumab in Patients With Recurrent Glioblastoma

This study is currently recruiting participants.
Verified September 2017 by M.D. Anderson Cancer Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02337686
First Posted: January 14, 2015
Last Update Posted: October 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
January 8, 2015
January 14, 2015
October 2, 2017
April 2015
April 2019   (Final data collection date for primary outcome measure)
  • Progression free survival at 6 months [ Time Frame: Baseline to 6 months ]
    Progression-free survival defined as the time from study enrollment until the time of first occurrence of disease progression, relapse, or death due to disease.
  • Immune Effector:Treg ratio measured at the time of surgery [ Time Frame: Measurement taken from tissue collected at time of surgery (Day 0) following 21 days of first treatment cycle ]
    Immune effector function measured in resected glioblastoma tissue after treatment with intravenously administered pembrolizumab monotherapy in the neoadjuvant setting in participants with recurrent glioblastoma. Pembrolizumab pharmacokinetics from blood correlated with tumor pharmacodynamic markers; Tumor tissue from surgical resection and peripheral blood evaluated longitudinally for pharmacodynamic effects including an increase of polyfunctional effector T cells:Treg ratio and improvement in the anti-tumor immune response. Defined Effector:Treg ratio>=5% is a success (i.e., favorable outcome) and <5% is a failure (i.e., unfavorable outcome).
Same as current
Complete list of historical versions of study NCT02337686 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Pharmacodynamic Study of Pembrolizumab in Patients With Recurrent Glioblastoma
Pharmacodynamic Study of Pembrolizumab in Patients With Recurrent Glioblastoma

The goal of this clinical research study is to learn if Keytruda (pembrolizumab) can help to control glioblastoma. The safety of this drug will also be studied.

This is an investigational study. Pembrolizumab is FDA approved and commercially available for the treatment of some types of melanoma. Its use against brain tumors in this study is investigational. The study doctor can explain how the study drug is designed to work.

Up to 20 participants will be enrolled in this study. All will take part at MD Anderson.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive pembrolizumab by vein over about 30 minutes on Days 1 and 21 of each 42-day study cycle.

On Day 22 of Cycle 1, you will be having surgery as part of routine care. After recovering from surgery (which may take around 14-21 days), you will start receiving pembrolizumab on Day 1 of Cycle 2.

Study Visits:

On Day 1 of Cycle 1:

  • You will have a physical exam.
  • Blood (about 2-3 teaspoons) will be drawn for routine tests, to check how well your blood clots, and to check your thyroid function. This blood draw will also include a pregnancy test if you can become pregnant.
  • Urine will be collected for routine tests.

On Day 21 of Cycle 1:

  • You will have a physical exam.
  • Blood (about 1 teaspoon) will be drawn for routine tests.
  • You will have an MRI of the brain to check the status of the disease.

On Day 22 of Cycle 1, you will have surgery to remove the tumor. You will sign a separate consent form that describes the procedure and risks. In addition to the surgery:

  • Blood (about 1 teaspoon) will be drawn for routine tests.
  • Blood (about 7 tablespoons) will be drawn for biomarker testing.
  • Leftover tumor tissue from surgery will be collected and used for biomarker testing.

As early as possible after surgery, you will have an MRI of the brain to check the status of the disease. The study staff will let you know when this can be done.

On Days 1 and 21 of Cycles 2 and beyond:

  • You will have a physical exam.
  • Blood (about 1 teaspoon) will be drawn for routine tests.

On Day 1 of Cycles 3, 6, and 9, blood (about 7 tablespoons) will also be drawn for biomarker testing.

On Day 1 of Cycles 3 and beyond, you will have an MRI of the brain to check the status of the disease.

At any time during the study, extra tests may be performed or the tests above may be repeated if the study doctor thinks it is needed. The study doctor will tell you more about any extra tests.

Length of Treatment:

You may continue receiving pembrolizumab for up to 2 years. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on this study will be over after follow-up.

End-of-Treatment Visit:

About 30 days after your last study drug dose, you will visit the clinic. At this visit::

  • You will have a physical exam.
  • Blood (about 2 teaspoons) will be drawn for routine tests.

If you stop the study drug because of intolerable side effects, every 8 weeks after your last study drug dose, you will have an MRI of the brain to check the status of the disease.

If the disease gets worse, blood (about 7 tablespoons) will be drawn for biomarker testing.

Follow-Up:

Every 3 months after the end-of-treatment visit, the study staff will call and ask how you are feeling and ask about any new cancer treatments you may be receiving. These calls should take about 5-10 minutes each time.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Brain Tumor
  • Glioblastoma
  • Cancer
  • Drug: Pembrolizumab
    Up to 2 doses of 200 mg IV prior to surgery (Day -21 and Day -1, prior to the surgery on Day 0); continued after recovery from surgery (approximately 2-3 weeks) every 3 weeks until disease progression or development of unacceptable toxicities.
    Other Names:
    • Keytruda
    • MK-3475
  • Procedure: Surgery
    Routine care surgery (reoperation) performed Day 0 for tumor progression.
Experimental: Pembrolizumab
Pembrolizumab 200 mg, intravenously (IV) once every 3 weeks prior to surgery for two doses and then restarting 200 mg every 3 weeks following surgical resection. Cycles defined as every 42 days.
Interventions:
  • Drug: Pembrolizumab
  • Procedure: Surgery
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
April 2019
April 2019   (Final data collection date for primary outcome measure)

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 histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma). Participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made.
  4. Patients must be at first or second relapse and clinically require reoperation for tumor progression within 4 to 6 weeks. Note: Relapse is defined as progression following initial therapy (i.e., radiation, chemotherapy, or radiation+ chemotherapy). If the participant had a surgical resection for relapsed disease and no antitumor therapy instituted for up to 12 weeks, this is considered one relapse. For participants who had prior therapy for a low grade glioma, the surgical diagnosis of a high grade glioma will be considered first relapse.
  5. Have measurable disease consisting of a minimal volume of 1 cm3.
  6. Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion.
  7. Have a performance status of >/= 60 on the KPS.
  8. Stable dose of steroids for 5 days, no more than 2 mg dexamethasone (or equivalent) total per day
  9. Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 14 days prior to registration. 1) Hematological : Absolute neutrophil count (ANC) >/=1,500 /mcL; Platelets >/=100,000 / mcL; Hemoglobin >/= 9 g/dL or >/= 5.6 mmol/L. 2) Renal: Serum creatinine </= 1.5 X upper limit of normal (ULN) 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 > 1.5 X institutional ULN.
  10. (9. continued) 3) 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) </= 2.5 X ULN OR </= 5 X ULN for subjects with liver metastases. 4) Coagulation: International Normalized Ratio (INR) or Prothrombin Time (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; 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 serum pregnancy test.
  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. Has been treated previously with bevacizumab
  2. Has tumor localized primarily to the brainstem or spinal cord.
  3. Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced delivery.
  4. Is currently participating in or has participated in a study of an investigational agent or using an investigational device 4 weeks since last dose of agent administration.
  5. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy > 2 mg of dexamethasone total per day or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  6. 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.
  7. 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 alopecia, </= Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  8. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
  9. Has known carcinomatous meningitis, extracranial disease, or multifocal disease.
  10. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
  11. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  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 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, anti-PD-L2, anti-CD137 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Testing not required.
  18. Has known history of Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). Testing not required.
  19. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact: John DeGroot, MD 713-792-2883
United States
 
 
NCT02337686
2014-0820
NCI-2015-00174 ( Registry Identifier: NCI CTRP )
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
Merck Sharp & Dohme Corp.
Study Chair: John DeGroot, MD M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP