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High Grade GliomaEarly Phase 1NCT04220892

Pilot Study of Pembrolizumab Combined With Pemetrexed or Abemaciclib for High Grade Glioma

A Early Phase 1 study testing Pembrolizumab, Pemetrexed and Abemaciclib in people with High Grade Glioma, run by Jose Carrillo at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this study is to evaluate any preliminary evidence of anticancer activity of pembrolizumab combined with either pemetrexed or abemaciclib when used following surgery and before standard therapy with radiation and temozolomide in patients with newly diagnosed high grade glioma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
High Grade Glioma
What is being tested?
Pembrolizumab, Pemetrexed and Abemaciclib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
8 Jul 2020to 8 Jul 2020
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participant or their legal representative has the ability to provide informed consent.
  • Participant has the willingness to comply with all study procedures and availability for the duration of the study.
  • Participant is being evaluated for a potential, or known, diagnosis of high grade glioma.
  • Note:Participant must have a diagnosis of high grade (WHO Grade III or IV) glioma following brain surgery to proceed with study treatment.
  • Participant is a candidate for brain surgery.
  • Participant is male or female, ≥ 18 years of age.
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  • Participant has a Karnofsky Performance Status ≥ 60%.
  • Participant has adequate organ function:
  • ANC at least 1.5 x 10^9/L or greater.
  • Platelets at least 100 x 10^9/L or greater.
  • Hemoglobin at least 8 g/dL or greater.
  • Total bilirubin 1.5 x upper limit of normal (ULN) or lower.
  • ALT and AST 3 x ULN or lower.
  • Serum creatinine 1.5 x ULN or lower.
  • Additional Inclusion Criteria for Arm 1 only:
  • Participant has the ability to interrupt nonsteroidal anti-inflammatory (NSAIDS) 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of Pemetrexed.
  • Participant has the ability to take folic acid, Vitamin B12, and dexamethasone according to protocol.
  • Creatinine clearance ≥ 45 mL/min (calculated using standard Cockcroft and Gault formula).
  • Additional Inclusion Criteria for Arm 1 only:
  • 1. Participant is able to swallow oral medications.

Who cannot join

  • Participant has received prior anti-cancer treatment for high-grade glioma.
  • Participant has a diagnosis of immunodeficiency or active autoimmune disease.
  • Participant is receiving chronic systemic steroid therapy in dosing exceeding 8 mg daily of dexamethasone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. This is assessed after surgery, prior to starting drug treatment.
  • Participant has received a live vaccine within 28 days prior to the first dose of study agent. Examples of live vaccines include, but are not limited to measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), typhoid vaccine, and intranasal influenza vaccines (e.g., FluMist®).
  • Participant has a severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study intervention, including, but not limited to:
  • Uncontrolled diabetes;
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  • Renal disease that requires dialysis;
  • Pulmonary disorder requiring supplemental oxygen to keep saturation >95% and the situation is not expected to resolve within 2 weeks;
  • Severe dyspnea at rest or requiring oxygen therapy;
  • Interstitial lung disease;
  • History of major surgical resection involving the stomach or small bowel;
  • Preexisting Crohn's disease;
  • Ulcerative colitis;
  • Uncontrolled vasculitis and/or disease with known vasculitis;
  • Preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea;
  • Psychiatric illness/social situations that would limit compliance with study requirements.
  • Participant has an active bacterial infection requiring intravenous antibiotics at time of initiating study treatment, fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C).
  • Participant has a personal history or presence of any of the following cardiovascular conditions:
  • Syncope of cardiovascular etiology;
  • Ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation);
  • Myocardial infraction within 6 months of investigational product administration;
  • Unstable angina;
  • Sudden cardiac arrest;
  • Congestive heart failure (New York Heart Association classification ≥ 3).
  • Participant is a female of childbearing potential who is pregnant or nursing.
  • Additional Exclusion Criteria for Arm 1 only:
  • Participant has third space fluid which cannot be controlled by drainage. For patients who develop or have baseline clinically significant pleural or peritoneal effusions (on the basis of symptoms or clinical examination) before or during initiation of pemetrexed therapy, consideration should be given to draining the effusion prior to dosing. However, if, in the investigator's opinion, the effusion represents progression of disease, the patient should be discontinued from study therapy.
  • Transaminases greater than 3.0 x ULN, except in presence of known hepatic metastasis, wherein may be up to 5 x ULN.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • John Wayne Cancer Institute

    Santa Monica, California, 90404

Other trials in United States

About this study

Official title: Pilot Study of Pembrolizumab Combined With Pemetrexed or Abemaciclib for the Treatment of Patients With High Grade Glioma

The purpose of this study is to evaluate any preliminary evidence of anticancer activity of pembrolizumab combined with either pemetrexed or abemaciclib when used following surgery and before standard therapy with radiation and temozolomide in patients with newly diagnosed high grade glioma.

Additional aims of the study are to:

  • Find out the side effects (good and bad) of pembrolizumab combined with pemetrexed or abemaciclib;
  • • Evaluate tumor characteristics by collecting brain tumor tissue samples.
  • Measure the amount of pembrolizumab, pemetrexed, and/or abemaciclib that gets in the body by collecting blood and cerebrospinal fluid.
  • Look at biomarkers (biochemical features that can be used to measure the progress of disease or the effects of a drug) in blood and cerebrospinal fluid if available.
Read the detailed description

This is a prospective, open-label, multi-arm exploratory study of pembrolizumab in combination with pemetrexed or abemaciclib for the treatment of adult patients with newly diagnosed high grade glioma. Patients having a clinically planned surgical procedure (biopsy or cytoreduction) for a suspected diagnosis of high grade glioma will be approached for participation in this study. Tumor tissue obtained from surgery will be used for histological diagnosis and clinical molecular profiling, and excess tumor tissue may be collected for potential correlative studies. A small sample of blood and cerebrospinal fluid (CSF) for research will also be collected.

Once a diagnosis of high grade glioma is confirmed, the patient will be allocated to either Treatment Arm 1 (pembrolizumab + pemetrexed), or Treatment Arm 2 (pembrolizumab + abemaciclib). Treatment will be started approximately 7-42 days following surgery once the patient has recovered from surgery. Routine clinical evaluations will be performed prior to treatment initiation and throughout treatment as clinically indicated. Radiographic brain imaging will be performed approximately 21-42 after treatment initiation and then routinely for medical management. Tumor response will be assessed according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) Working Group criteria.

Treatment may continue until the patient experiences unacceptable toxicity or clear disease progression. The determination of whether to stop treatment due to disease progression will be based on the investigator's evaluation of the patient's clinical and radiographic condition, taking into consideration the interpretation of localized inflammatory responses that can mimic radiographic features of tumor progress. Patients discontinuing treatment will be directed by their treating physician to either receive a different treatment regimen (e.g., standard radiation therapy with or without chemotherapy) or undergo a clinically-indicated cytoreductive surgery. If another treatment is started, clinical evaluations and response assessments will continue as clinically-indicated and blood and CSF will be collected after the first month, then every three months.

Keywords
Immunotherapy, Pembrolizumab, Pemetrexed, Abemaciclib, Cyclin-dependent kinase 4 (CDK4), Cyclin-dependent kinase 6 (CDK6), Folate antimetabolite
Medical subject headings
Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called Keytruda

    200 mg intravenous (IV) every 3 weeks

  • PemetrexedDrug

    Also called Alimta

    900 mg/m^2 IV every 3 weeks. Supportive medications of ibuprofen, folic acid, vitamin B12, and dexamethasone.

  • AbemaciclibDrug

    Also called Verzenio

    150 mg twice a day, by mouth.

Study groups in NCT04220892
Study groupRoleWhat they receive
Pembrolizumab plus PemetrexedExperimentalPembrolizumab plus Pemetrexed
Receives: Drug: Pembrolizumab; Drug: Pemetrexed
Pembrolizumab plus AbemaciclibExperimentalPembrolizumab plus Abemaciclib
Receives: Drug: Pembrolizumab; Drug: Abemaciclib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Tumor response rates

    Evidence of anti-tumor activity as measured according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria.

    Measured: one year

Secondary outcomes (5)

  1. Toxicity assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03.

    Proportion of patients experiencing adverse events

    Measured: one year

  2. Progression free survival (PFS)

    The duration of time from start of treatment until objective tumor progression or death.

    Measured: one year

  3. Overall survival (OS)

    The duration of time from start of treatment to death.

    Measured: four years

  4. Levels of immunotherapeutic agents in specimens

    Immunotherapeutic drug levels in specimens.

    Measured: approximately 3 months

  5. Change in gene signature of tumor tissue after treatment

    Comparison of genetic analysis of tumor tissue collected before and after study treatment.

    Measured: approximately 6 months to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jan 2020
  2. Study start8 Jul 2020 (estimated)
  3. Primary completion8 Jul 2020 (estimated)
  4. Study completion8 Jul 2020 (estimated)

Why it stopped: One of the study drugs will no longer be supplied by manufacturer and the pembrolizumab + abemaciclib study arm is removed due to toxicity seen in other trials.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04220892
Sponsor's protocol ID
JWCI-18-0702 (I3Y-US-I011)
Status last verified
Jul 2020
First submitted
26 Nov 2019
Last updated
31 Jul 2020
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Pembrolizumab, Pemetrexed and Abemaciclib in people with High Grade Glioma, run by Jose Carrillo at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 31 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tumor response rates (time frame: one year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04220892.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2020.

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