Trial record 4 of 15 for:    HSPPC-96

Radiation Therapy Plus Temozolomide and Pembrolizumab With and Without HSPPC-96 in Newly Diagnosed Glioblastoma (GBM)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2017 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT03018288
First received: January 11, 2017
Last updated: NA
Last verified: January 2017
History: No changes posted
  Purpose

Background:

GBM refers to a specific kind of brain cancer called glioblastoma. The standard treatment for GBM is radiation plus temozolomide, an oral chemotherapy drug. Pembrolizumab is an immune therapy that is now used to treat other cancers. The addition of pembrolizumab to the standard treatment of radiation and temozolomide has been shown to be well tolerated.. Researchers want to see if adding a vaccine made from the person s own tumor will improve the effect of the pembrolizumab. The vaccine which is developed from fresh tumor taken at the time of surgery is called HSPPC-96.

Objectives:

To see if the adding pembrolizumab and HSPPC-96 improves the standard treatment for glioblastoma multiforme.

Eligibility:

Adults at least 18 years old with glioblastoma.

Design:

Participants will be screened with typical cancer tests:

Brain scan

Medical history

Blood and urine tests

Questions about quality of life and symptoms

These tests will be repeated throughout the study.

Participants will have surgery to remove their tumor. A tissue sample from the tumor will be sent to a lab. A vaccine will be made from it.

Some participants will get pembrolizumab and vaccine. Some will get pembrolizumab and placebo. Participants will not know which they get.

Participants will get radiation for 6 weeks.

Participants will take temozolomide by mouth before each treatment.

Participants will get pembrolizumab by IV for 30 minutes 3 times over the radiation cycle.

Participants will keep taking the 2 drugs every few weeks for about a year. Some may take pembrolizumab for an additional year.

Most participants will get the vaccine or placebo after radiation. They will get it 5 times over 6 weeks. Some participants will continue to get the vaccine every few weeks for 1 or 2 years.

Participants will repeat the screening tests when they stop study treatment. They will also have follow-up phone calls.


Condition Intervention Phase
Glioblastoma
Drug: Pembrolizumab
Biological: HSPPC-96
Drug: Temozolomide
Other: Placebo
Radiation: radiation treatment
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind Phase II Trial of Radiation Therapy Plus Temozolomide and Pembrolizumab With and Without HSPPC-96 in Newly Diagnosed Glioblastoma (GBM)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To determine whether the one-year overall survival (OS) is improved in newly diagnosed MGMT unmethylated GBM patients treated with RT + TMZ + Pembrolizumab followed by Pembrolizumab + TMZ +/- HSPPC-96 x 6 cycles (1 cycle is 9 weeks) months. [ Time Frame: one year ]

Secondary Outcome Measures:
  • Progression Free Survival-6 ((PFS-6) (percentage of patients alive and progression-free at 6 months post registration) will be defined from the time of registration to the time of confirmed progression in cases where this might be unclear, patie... [ Time Frame: 6 months ]
  • Overall Survival (OS) OS-6, 12 and 24 (percentage of patients alive at 6, 12 and 24 months respectively). These quantities will be determined from the level of the Kaplan-Meier curves at these time points. [ Time Frame: 6, 12, 24 months ]
  • Response will be determined by tables below using RANO as main criteria but also assess by iRANO. If a lesion is 25% larger but there remains a question as to disease progression or pseudoprogression due to treatment, the patient can remain on t... [ Time Frame: 6, 12, 24 months ]

Estimated Enrollment: 108
Study Start Date: January 2017
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RT+TMZ+Pembrolizumab+HSPPC-96
tumor meets criteria randomized vaccine group
Drug: Pembrolizumab
Pembrolizumab at 200mg will be administered on day 1 as a 30 minute IV infusion (prior to RT) every 3 weeks during RT on days 1, 22 and 43. At one year, if patients are doing well they may continue pembolizumab for 12 more months alone or in conjunction with HSPPC-96 or placebo vaccine if any is available.
Biological: HSPPC-96
One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine or placebo. HSPPC-96 vaccine or placebo will then be given 21 days after the day 5 dose of TMZ. HSPPC-96 vaccine or placebo vaccine will be given for 6 cycles or until supply runs out. Patients who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 or placebo vaccine if any is available.
Drug: Temozolomide
TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m2. Post RT: The starting TMZ dose will be 150 mg/m2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.
Radiation: radiation treatment
All patients will be treated with standard RT to approximately 60 Gy (180 Gy x 33 fractions or 200 Gy x 30 fractions).
Placebo Comparator: RT+TMZ+Pembrolizumab +Placebo
tumor meets criteria randomized placebo group
Drug: Pembrolizumab
Pembrolizumab at 200mg will be administered on day 1 as a 30 minute IV infusion (prior to RT) every 3 weeks during RT on days 1, 22 and 43. At one year, if patients are doing well they may continue pembolizumab for 12 more months alone or in conjunction with HSPPC-96 or placebo vaccine if any is available.
Drug: Temozolomide
TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m2. Post RT: The starting TMZ dose will be 150 mg/m2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.
Other: Placebo
One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine or placebo. HSPPC-96 vaccine or placebo will then be given 21 days after the day 5 dose of TMZ. HSPPC-96 vaccine or placebo vaccine will be given for 6 cycles or until supply runs out. Patients who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 or placebo vaccine if any is available.
Radiation: radiation treatment
All patients will be treated with standard RT to approximately 60 Gy (180 Gy x 33 fractions or 200 Gy x 30 fractions).
Experimental: RT+TMZ+Pembrolizumab
tumor does not meet criteria (ancillary group)
Drug: Pembrolizumab
Pembrolizumab at 200mg will be administered on day 1 as a 30 minute IV infusion (prior to RT) every 3 weeks during RT on days 1, 22 and 43. At one year, if patients are doing well they may continue pembolizumab for 12 more months alone or in conjunction with HSPPC-96 or placebo vaccine if any is available.
Drug: Temozolomide
TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m2. Post RT: The starting TMZ dose will be 150 mg/m2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.
Radiation: radiation treatment
All patients will be treated with standard RT to approximately 60 Gy (180 Gy x 33 fractions or 200 Gy x 30 fractions).

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Pre Surgery (Step 1)

  • MRI findings consistent with a histologically confirmed newly diagnosed GBM that has not been treated and would benefit from further surgical resection. As vaccine needs to be generated from the patient s tumor, patients will need to be identified prior to definitive surgery.
  • Age greater than or equal to 18 years on day of signing informed consent.
  • Karnofsky performance status greater than or equal to 70%.
  • Tumor must be supratentorial only.
  • Stereotactic biopsy will not be allowed unless there is plans for second surgery to remove greater than or equal to 80 % of the tumor.
  • No prior treatment with radiation or chemotherapy for their GBM.
  • No prior treatment with carmustine wafers.

Post-Surgery for vaccine or placebo (Step 2):

  • Pathology must be a GBM, MGMT promoter region determined to be unmethylated and IDH wild type. Greater than or equal to 80 % resection of contrast enhanced tumor on post operative MRI is required for randomization, otherwise treatment will occur on the ancillary arm.
  • Treatment must be initiated greater than or equal to 14 days and < 6 weeks from surgery.
  • Craniotomy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of radiation. Radiation must start within 6 weeks of surgery.
  • Dexamethasone dose should be less than or equal to 4 mg/day or steroid equivalent prior to starting treatment. If higher doses are needed, consult with Study Chair.
  • Female subjects of childbearing potential should have a negative urine or serum pregnancy within 7 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a negative serum pregnancy test will be required.
  • Patients must have adequate organ and bone marrow function within 14 days prior to registration, as defined below:

    • Absolute neutrophil count (ANC) > 1.5 (SqrRoot) 10(9)/L; platelet count > 100 (SqrRoot) 10(9)/L; and hemoglobin (Hb) >9.0 g/dL within 7 days prior to enrollment. Note: The use of transfusion or other intervention to achieve Hb greater than or equal to 9.0 g/dL is acceptable.
    • Total bilirubin < 1.5 (SqrRoot) ULN (except in patients diagnosed with Gilbert s disease)
    • AST (SGOT), ALT (SGPT), and alkaline phosphatase (ALP) < 2.5 (SqrRoot) ULN
    • Serum creatinine < 1.5 (SqrRoot) ULN
    • International normalized ratio (INR), prothrombin time (PT), or activated partial thromboplastin time (APTT) as follows: In the absence of therapeutic intent to anticoagulate the patient: INR < 1.5 or PT < 1.5(SqrRoot) ULN or aPTT < 1.5(SqrRoot) ULN. In the presence of therapeutic intent to anticoagulate the patient: INR or PT and aPTT within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose of anticoagulants for at least 2 weeks before registration.
  • Females of child-bearing potential (FOCBP) and males must agree to use two adequate contraception methods (give examples, e.g. hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 120 days following completion of therapy. Should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Male patients who father a child should notify the treating physician.

NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

  1. Has not undergone a hysterectomy or bilateral oophorectomy
  2. Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)

    • Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study.
    • Diagnosis must be made by surgical excision.
    • Patients should not be on antibiotics for any infection but post operative antibiotics are allowed if used prophylactically but should be completed prior to starting RT.

EXCLUSION CRITERIA:

  • Patients who are receiving any other investigational agents.
  • Known history of immunodeficiency (HIV 1/2 antibodies). This medical entity can be exacerbated by PD-1 blockade.
  • Any form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment excluding steroids. Attempts should be made to have patient on lowest possible dose of steroids. These medical entities can be exacerbated by PD-1 blockade.
  • History of another malignancy in the previous 3 years, with a disease-free interval of < 3 years. 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.
  • 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 chronic 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 will not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen s syndrome will not be excluded from the study.
  • Has a history of interstitial lung disease, non-infectious pneumonitis or pneumonitis.
  • Has an active infection requiring systemic antibiotics within 10 days of surgery.
  • 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.

Examples include:

  • Hypertension (defined as 160/95) that is not controlled on medication
  • Ongoing or active infection requiring systemic treatment
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations or substance abuse disorders that would limit compliance with study requirements
  • Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient s safety or study endpoints.

    • 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.
    • The effects of pembrolizumab and HSPPC-96 on the developing human fetus are unknown. For this reason and because checkpoint inhibitors and immunotherapeutic vaccines as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry,and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
    • 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).
    • On treatment for Hepatitis B or Hepatitis C or history of TB.
    • Has received a live vaccine within 30 days prior to the first dose of trial treatment
    • Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Pembrolizumab are not eligible. Known hypersensitivity to any excipients of Pembrolizumab.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03018288

Contacts
Contact: Christine M Bryla, R.N. (240) 760-6007 brylacm@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Not yet recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Mark R Gilbert, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03018288     History of Changes
Other Study ID Numbers: 170034  17-C-0034 
Study First Received: January 11, 2017
Last Updated: January 11, 2017

Keywords provided by National Institutes of Health Clinical Center (CC):
Malignant Gliomas
Immunotherapy

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Pembrolizumab
Temozolomide
Dacarbazine
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on January 19, 2017