Gynecologic NeoplasmsEarly Phase 1NCT02728830
A Study of Pembrolizumab on the Tumoral Immunoprofile of Gynecologic Cancers
A Early Phase 1 study testing Pembrolizumab in people with Gynecologic Neoplasms and Epithelial Ovarian Cancer, run by AA Secord at 1 site in United States.
Trial summary
The ultimate goal of the study is to identify potential biomarkers, immune gene expression signatures, and co-stimulatory pathways that may be used to understand the effect of immune checkpoint inhibitors on gynecologic cancers. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Gynecologic Neoplasms, Epithelial Ovarian Cancer, Uterine Endometrial Cancer
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2016to 31 Jan 2022
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have histologically or cytologically confirmed gynecologic tumor of müllerian origin, specifically epithelial ovarian, fallopian tube, primary peritoneal, or uterine endometrial cancer.
- Have disease amenable to surgical resection.
- Be willing and able to provide written informed consent for the trial.
- Be at least 18 years of age on day of signing informed consent.
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement of the investigator.
- Have a performance status of 0 or 1 on the ECOG Performance Scale.
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- Demonstrate adequate organ function as defined below. All screening labs should be performed within 10 days of study drug administration:
- 7a. ANC ≥ 1,500/mcL
- 7b. Platelets ≥ 100,000/mcL
- 7c. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
- 7d. Serum creatinine ≤ 1.5 times the upper limit of normal or calculated creatinine clearance ≥ 60 mL/min for subject with creatinine levels > 1.5 times institutional upper limit of normal
- 7e. Serum total bilirubin ≤ 1.5 times the upper limit of normal or direct bilirubin ≤ the upper limit of normal with total bilirubin levels > 1.5 times upper limit of normal
- 7f. AST and ALT ≤ 2.5 times the upper limit of normal or ≤ 5 times the upper limit of normal for subjects with liver metastases
- 7g. Albumin > 2.5 mg/dL
- 7h. International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- 7i. Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- 8. Female subjects 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.
- 9. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity until planned hysterectomy/oophorectomy. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
Who cannot join
- Is currently participating and receiving a 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 study drug administration.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study drug administration.
- Has a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients.
- 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.
- Has received prior chemotherapy, targeted small molecule therapy, or radiation therapy for the current gynecologic malignancy.
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- NOTE: Subjects who have received treatment for a prior unrelated malignancy must have recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
- NOTE: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- 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 that has undergone potentially curative therapy, or in situ cervical cancer.
- 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 study drug administration 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 drug administration. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- 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.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- 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.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days of planned start of study therapy. NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Study Investigating the Effect of Pembrolizumab on the Tumoral Immunoprofile of Gynecologic Cancers of Mullerian Origin
The ultimate goal of the study is to identify potential biomarkers, immune gene expression signatures, and co-stimulatory pathways that may be used to understand the effect of immune checkpoint inhibitors on gynecologic cancers.
Read the detailed description
Epithelial gynecologic malignancies are tumors of müllerian origin, which include ovarian, endometrial, fallopian tube, and primary peritoneal cancers, and account for >70,000 new diagnoses and >22,000 deaths per year in the United States alone. Treatment typically consists of a thorough cytoreductive and staging surgery in combination with platinum/taxane chemotherapy. Newer approaches adding anti-angiogenic therapies to chemotherapy have resulted in moderate improvements in recurrence free survival. However, despite these aggressive treatments, the majority of women with advanced stage at diagnosis will experience relapse. Unfortunately, relapsed disease is incurable and women ultimately die of their disease despite maximal efforts at cancer control using subsequent chemotherapy or targeted agents. There has been significant interest in incorporating immune checkpoint therapies in the treatment of gynecologic malignancies, especially given the durable remissions associated with these therapies in the treatment of melanoma and early indications of durable responses in recurrent ovarian cancer. At this time, little is known about whether or how to combine chemotherapy, anti-angiogenic therapies, and immunologic therapies for maximal benefit. Understanding the tumor microenvironment, particularly immune and angiogenic factors that contribute to tumor survival, as well as the changes that occur in response to immunotherapy is critical to identify favorable biomarker profiles which could lead to improved prognostic outcomes and inform the development and sequencing of therapies to maximize benefit.
- Conditions
- Gynecologic Neoplasms, Epithelial Ovarian Cancer, Uterine Endometrial Cancer, Fallopian Tube Cancer, Peritoneal Cancer
- Being tested
- Pembrolizumab
- Keywords
- gynecologic cancers, mullerian cancers, tumoral immunoprofile
- Medical subject headings
- Genital Neoplasms, Female, Carcinoma, Ovarian Epithelial, Endometrial Neoplasms, Fallopian Tube Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
Pembrolizumab 200mg IV
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab | Experimental | Subjects will receive one dose of 200mg pembrolizumab by IV 14-21 days prior to surgery. Subjects will undergo standard surgical cytoreductive surgery as deemed appropriate by their gynecologic oncologist, followed by standard adjuvant chemotherapy for their cancer as deemed appropriate by their treating physician.
If subject's disease does not get worse following standard of care chemotherapy, they will receive pembrolizumab in the maintenance setting every three weeks for up to a year.
If subject's disease returns after completing a year of pembrolizumab and they have not had adverse reactions to pembrolizumab they may be eligible to continue receiving pembrolizumab for an additional year in the second course phase. Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Tumor Immune Infiltrates as Measured by PD-L1 Modified H-Score
This outcome measures the change in tumor immune infiltrates post-pembrolizumab versus pre-pembrolizumab as measured by the PD-L1 Modified H-score.
Histological score (H-score) is a score that is comprised of intensity and percentage of staining and is used for assessing amount of protein (in this case PD-L1) present in a tissue sample. H-score is determined by adding of the percentages of cell staining at each intensity level multiplied by the membrane intensity of staining (0 (no staining), 1+ (weak staining), 2+ (medium staining), 3+(strong staining)).
The H-score has a range of 0 to 300. Lower H-scores represent lower expression of PD-L1 in the tumor sample, while higher scores represent stronger expression of PD-L1 in the tumor samples.
Measured: Baseline and 14-21 Days
Secondary outcomes (1)
Toxicity Profile: Frequency and Severity of Adverse Events as Assessed by CTCAE
Frequency and severity of adverse events associated with pembrolizumab when given to patients with newly diagnosed gynecologic cancers of müllerian origin prior to standard surgical therapy and as maintenance therapy after completion of chemotherapy. All events experienced within the AE reporting time frame deemed probably, possibly, or definitely related to study drug above the reporting threshold of 4%. Categorized by grade and frequency, defined using CTCAE 4.0 event name and grading.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2016 (estimated)
- Study startJun 2016
- Primary completion31 Jan 2019
- Study completion31 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gynecologic NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- AA Secord
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, AA Secord, Duke University
- Investigators
- Angeles A Secord, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02728830
- Sponsor's protocol ID
- Pro00068544
- Status last verified
- Feb 2024
- First submitted
- 31 Mar 2016
- Last updated
- 21 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study Investigating the Effect of Pembrolizumab on the Tumoral Immunoprofile of Gynecologic Cancers of Mullerian Origin
- ClinicalTrials.gov ID
- NCT02728830
- Acronym / sponsor ID
- Pro00068544
- Conditions
- Gynecologic Neoplasms, Epithelial Ovarian Cancer, Uterine Endometrial Cancer, Fallopian Tube Cancer, Peritoneal Cancer
- Keywords
- gynecologic cancers, mullerian cancers, tumoral immunoprofile
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- AA SecordUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Jun 2016
- Primary completion
- 31 Jan 2019 (actual)
- Study completion
- 31 Jan 2022 (actual)
- First posted
- 5 Apr 2016 (estimated)
- Results
- Posted 9 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The ultimate goal of the study is to identify potential biomarkers, immune gene expression signatures, and co-stimulatory pathways that may be used to understand the effect of immune checkpoint inhibitors on gynecologic cancers.
Detailed description
Epithelial gynecologic malignancies are tumors of müllerian origin, which include ovarian, endometrial, fallopian tube, and primary peritoneal cancers, and account for >70,000 new diagnoses and >22,000 deaths per year in the United States alone. Treatment typically consists of a thorough cytoreductive and staging surgery in combination with platinum/taxane chemotherapy. Newer approaches adding anti-angiogenic therapies to chemotherapy have resulted in moderate improvements in recurrence free survival. However, despite these aggressive treatments, the majority of women with advanced stage at diagnosis will experience relapse. Unfortunately, relapsed disease is incurable and women ultimately die of their disease despite maximal efforts at cancer control using subsequent chemotherapy or targeted agents. There has been significant interest in incorporating immune checkpoint therapies in the treatment of gynecologic malignancies, especially given the durable remissions associated with these therapies in the treatment of melanoma and early indications of durable responses in recurrent ovarian cancer. At this time, little is known about whether or how to combine chemotherapy, anti-angiogenic therapies, and immunologic therapies for maximal benefit. Understanding the tumor microenvironment, particularly immune and angiogenic factors that contribute to tumor survival, as well as the changes that occur in response to immunotherapy is critical to identify favorable biomarker profiles which could lead to improved prognostic outcomes and inform the development and sequencing of therapies to maximize benefit.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Drug: PembrolizumabSubjects will receive one dose of 200mg pembrolizumab by IV 14-21 days prior to surgery. Subjects will undergo standard surgical cytoreductive surgery as deemed appropriate by their gynecologic oncologist, followed by standard adjuvant chemotherapy for their cancer as deemed appropriate by their treating physician. If subject's disease does not get worse following standard of care chemotherapy, they will receive pembrolizumab in the maintenance setting every three weeks for up to a year. If subject's disease returns after completing a year of pembrolizumab and they have not had adverse reactions to pembrolizumab they may be eligible to continue receiving pembrolizumab for an additional year in the second course phase. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Have histologically or cytologically confirmed gynecologic tumor of müllerian origin, specifically epithelial ovarian, fallopian tube, primary peritoneal, or uterine endometrial cancer.
- Have disease amenable to surgical resection.
- Be willing and able to provide written informed consent for the trial.
- Be at least 18 years of age on day of signing informed consent.
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement of the investigator.
Key exclusion criteria (20 listed)
- Is currently participating and receiving a 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 study drug administration.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study drug administration.
- Has a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: KeytrudaPembrolizumab 200mg IV | Drug | Pembrolizumab |
Primary outcome
Change in Tumor Immune Infiltrates as Measured by PD-L1 Modified H-Score
Time frame: Baseline and 14-21 Days
This outcome measures the change in tumor immune infiltrates post-pembrolizumab versus pre-pembrolizumab as measured by the PD-L1 Modified H-score. Histological score (H-score) is a score that is comprised of intensity and percentage of staining and is used for assessing amount of protein (in this case PD-L1) present in a tissue sample. H-score is determined by adding of the percentages of cell staining at each intensity level multiplied by the membrane intensity of staining (0 (no staining), 1+ (weak staining), 2+ (medium staining), 3+(strong staining)). The H-score has a range of 0 to 300. Lower H-scores represent lower expression of PD-L1 in the tumor sample, while higher scores represent stronger expression of PD-L1 in the tumor samples.
1 secondary outcome
Toxicity Profile: Frequency and Severity of Adverse Events as Assessed by CTCAE
Time frame: 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angeles A Secord, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Pembrolizumab in people with Gynecologic Neoplasms and Epithelial Ovarian Cancer, run by AA Secord 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 18 inclusion and 20 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: finished, as of the sponsor's last update on 21 Feb 2024. 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?
Yes. Results are posted in the registry (first posted 9 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Tumor Immune Infiltrates as Measured by PD-L1 Modified H-Score (time frame: Baseline and 14-21 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Feb 2024.