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Epithelial Ovarian CancerPhase 2NCT02900560

Study of Pembrolizumab With or Without CC-486 in Patients With Platinum-resistant Ovarian Cancer

A Phase 2 study testing CC-486 and Pembrolizumab in people with Epithelial Ovarian Cancer, run by Translational Research in Oncology at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of the study is to determine the optimal dose of CC-486 (oral azacitidine) in combination with pembrolizumab for the treatment of platinum-resistant/refractory Epithelial Ovarian Cancer (EOC). Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Epithelial Ovarian Cancer
What is being tested?
CC-486 and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
4 sitesUnited States
Study dates
20 Dec 2016to 27 May 2021
Phase
Phase 2
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

  • Signed and dated informed consent document obtained prior to initiation of any study-specific procedure and treatment (by the subject or a legally acceptable representative as per the local regulations).
  • Women ≥ 18 years old
  • Histologically confirmed Epitheilial Ovarian Cancer (EOC), Fallopian Tube Cancer (FTC) or Primary Peritoneal Cancer (PPC).
  • Received debulking surgery and preoperative and/or postoperative platinum-based frontline chemotherapy (intravenous and/or intraperitoneal) for the treatment of EOC/FTC/PPC.
  • Documented platinum-resistant or platinum-refractory disease. Platinum-resistant disease is defined as progression within < 6 months from completion of a minimum of 4 platinum frontline therapy cycles in the pre or postoperative setting (the date should be calculated from the last administered dose of platinum agent). Platinum-refractory is defined as disease that has recurred/progressed while receiving platinum-based frontline therapy.
  • Measurable disease according to Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST)
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  • Indication of systemic treatment for the relapsed EOC, FTC or PPC.
  • Subjects must have a tumor lesion that is amenable to an image-guided core biopsy and willingness to undergo two biopsies (baseline and 6 weeks after first dose of study treatment).
  • Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0 or 1.
  • Expected survival of more than 6 months.
  • Adequate organ function within 7 days prior to enrollment, as defined by the following criteria:
  • Absolute neutrophils count (ANC) ≥ 1.5 x 10E9/L, platelets ≥ 100 x 10E9/L, hemoglobin > 9 g/dL (without transfusion or erythropoiesis stimulating agents' dependency).
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN).
  • Total serum bilirubin ≤ 1.5 x ULN regardless of liver involvement secondary to tumor. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.
  • Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) < 2.0 x ULN or ≤ 5 X ULN for subjects with liver metastases.
  • 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
  • Partial Thromboplastin Time (PTT) or Activated Partial Thromboplastin Time (aPTT) ≤ 40 seconds unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • For women of childbearing potential, negative serum pregnancy test within 7 days of enrollment
  • Women of childbearing potential must agree to use acceptable methods of birth control starting with the screening visit and up to 120 days after the last dose of study treatment. Recommendation is for 2 effective contraceptive methods during the study. Adequate forms of contraception are double-barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral depo provera, or injectable contraceptives, intrauterine devices, and tubal ligation.
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

Who cannot join

  • Non-epithelial ovarian cancers, including malignant mixed Müllerian tumors.
  • Ovarian tumors with low malignant potential (i.e. borderline tumors).
  • Relapse/progression based solely on elevation of CA-125, in absence of measurable disease, according to irRECIST criteria.
  • More than 2 prior treatment regimens for the platinum-resistant/refractory relapsed EOC, FTC, or PTC, defined as investigational, chemotherapy, hormonal, biologic, or targeted therapy.
  • Any concurrent or previous malignancy within 5 years prior to enrollment except for adequately and radically treated basal or squamous skin cancer, or carcinoma in situ of the cervix, or other non-invasive/in-situ neoplasm. A subject with previous history of invasive malignancy (other than adequately and radically treated basal or squamous skin cancer or carcinomas in situ) is eligible provided that she has been disease free for more than 5 years.
  • Brain metastases (even if treated and/or stable), spinal cord compression, carcinomatous meningitis, or leptomeningeal disease.
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  • Prior systemic anticancer therapy within 4 weeks prior to enrollment or who has not recovered (i.e. ≤ Grade 1 or baseline grade) from adverse events due to a previously administered agent
  • Prior treatment with a monoclonal antibody within 4 weeks prior to enrollment or who has not recovered (i.e. ≤ Grade 1 or baseline grade) from adverse events due to agents administered more than 4 weeks earlier.
  • Diagnosis of immunosuppression or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment . The use of physiologic doses of corticosteroids may be approved after consultation with the sponsor.
  • Active autoimmune disease or history of autoimmune disease or syndrome that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Subjects with vitiligo or resolved childhood asthma/atopy will not be excluded.
  • Received live vaccines within 30 days prior to enrollment
  • Current or prior history of myelodysplastic syndrome, leukemia or clinically significant (as per Investigator judgment) bone marrow failure.
  • Uncontrolled systemic fungal, bacterial or viral infection at time of enrollment (defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment).
  • Known history of active TB (Bacillus Tuberculosis).
  • Known HIV infection or known history of Hepatitis B or known positivity for active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA [qualitative] is detected).
  • Known history of non-infectious pneumonitis that required steroids or has current pneumonitis (infectious or non-infectious).
  • Significant active cardiac disease within 6 months prior to enrollment, including but not limited to New York Heart Association class 4 cardiac heart failure, unstable angina, myocardial infarction
  • 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. Is or has an immediate family member (e.g. spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective Institutional Review Board (IRB) approval (by chair or designee) is given allowing exception to this criterion for a specific subject.
  • Any contraindication to oral agents or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the Investigator, would preclude adequate absorption.
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Prior treatment with any anti-Programmed Death (PD)-1, or PD-L1 or PD-L2 agent; or with azacitidine (any formulation) or any other hypomethylating agent; or with anti-cytoplasmic (CD) 137, or anti-cytotoxic T-Lymphocyte Associated Protein (CTLA)-4 antibody (including ipilimumab) or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  • Known or suspected hypersensitivity to azacitidine, pembrolizumab or the excipients of any of the study drugs (including mannitol). Known or suspected hypersensitivity to monoclonal antibodies.
  • Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks prior to enrollment .
  • Pregnant or lactating women or is expecting to conceive children or breastfeed within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.

Trial locations and contacts

4 sites in 1 country.

United States4 sites
  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • UCLA

    Los Angeles, California, 90095

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Phase II Randomized Study of Pembrolizumab With or Without Epigenetic Modulation With CC-486 in Patients With Platinum-resistant Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

The purpose of the study is to determine the optimal dose of CC-486 (oral azacitidine) in combination with pembrolizumab for the treatment of platinum-resistant/refractory Epithelial Ovarian Cancer (EOC).

Read the detailed description

This is an open-label, non-randomized, four-cohort study, in which intravenous pembrolizumab will be combined with 4 different schedules of administration of CC-486 (oral azacitidine), for the treatment of platinum-resistant/refractory (EOC). This is also a futility trial for the strategy to combine pembrolizumab and CC-486 in EOC. Eligible subjects will be treated in one of four cohorts of combined oral CC-486 and intravenous pembrolizumab (200 mg intravenous (IV) every 3 weeks in all cohorts) to evaluate the safety of each combination schedule and to have preliminary data on their efficacy. The primary objective is to establish the optimal dosing schedule for comparison with pembrolizumab alone.

Subjects will be assigned to a treatment cohort in the order they are enrolled in the study. In all subjects, tumor tissue will be obtained via image-guided core biopsy at study entry and 6 weeks after commencing treatment with CC-486. A cohort will remain open to accrual until five subjects treated on that cohort have completed two CC-486 cycles and have had the first post-baseline tumor burden assessment and both tumor biopsies performed and adequate paired tissue obtained. At least 5 evaluable subjects per cohort will be accrued over an estimated period of approximately 24 months.

Subjects will be treated in the assigned cohort until progressive disease based on Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST), unacceptable toxicity, consent withdrawal or the Investigator concludes that it is in the subject´s best interest to discontinue. Once 5 subjects in each cohort are considered evaluable for response, toxicity and treatment responses will be analyzed for each of the four cohorts and an optimal schedule will be selected.

This study includes mandatory tumor core biopsies for biomarkers research and mandatory whole blood sampling for deoxyribonucleic acid (DNA) methylation analyses.

Being tested
CC-486, Pembrolizumab
Medical subject headings
Carcinoma, Ovarian Epithelial

What participants receive

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

  • CC-486Drug

    Also called oral azacitidine

    CC-486 Intervention will depend on cohort enrolled in. 100 mg tablet

  • PembrolizumabBiological

    Also called Keytruda

    Pembrolizumab 200 mg IV every 21 days

Study groups in NCT02900560
Study groupRoleWhat they receive
Cohort 1Active comparatorCC-486 100 mg once a day, 21 days on, 7 days off combined with Pembrolizumab 200 mg IV every 21 days
Receives: Drug: CC-486; Biological: Pembrolizumab
Cohort 2Active comparatorCC-486 100 mg twice a day, 21 days on, 7 days off combined with Pembrolizumab 200 mg IV every 21 days
Receives: Drug: CC-486; Biological: Pembrolizumab
Cohort 3Active comparatorCC-486 300 mg once a day, 14 days on and 14 days off combined with Pembrolizumab 200 mg IV every 21 days
Receives: Drug: CC-486; Biological: Pembrolizumab
Cohort 4Active comparatorCC-486 300 mg once a day, 21 days on, 7 days off combined with Pembrolizumab 200 mg IV every 21 days
Receives: Drug: CC-486; Biological: Pembrolizumab

What is being measured

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

  1. Number of Subjects With Grade 3, 4, or 5 Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.03

    Safety evaluation: number of subjects with grade 3, 4, or 5 adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. This is an assessment of the frequency, severity and relationship to trial treatment of all adverse events that occurred while on trial. CTCAE is a standard classification and severity grading scale (from 1- mild to 5 - death) for adverse events in clinical trials and oncology settings.

    Measured: The average time period for patient participation was 30 weeks.

  2. Number of Subjects With Immune-related Partial Response (irPR), Immune-related Complete Response (irCR), Immune-related Stable Disease (irSD), Immune-related Progressive Disease (irPD), and Immune-related Not Evaluable (irNE) as Assessed by irRECIST.

    Efficacy evaluation: based on the Immune-related Objective Response Rate (irORR)/ Immune-related Disease Control Rate (irDCR) per Immune-Related Response Evaluation Criteria In Solid Tumor (irRECIST) criteria using the intent-to-treat (ITT) population (all patients who were enrolled in the study, regardless of whether they actually received study medication). The best overall response outcome (irCR/irPR/irSD/irPD/irNE) will be summarized and tabulated for ITT by cohort.

    Measured: The average time period for patient participation was 30 weeks.

  3. Number of Subjects With Treatment Emergent Adverse Events Related to CC-486 as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

    Safety evaluation: number of subjects with treatment emergent adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. This is an assessment of the frequency and relationship to trial treatment of all adverse events that occurred while on trial. CTCAE is a standard classification and severity grading scale (from 1- mild to 5 - death) for adverse events in clinical trials and oncology settings.

    Measured: The average time period for patient participation was 30 weeks.

  4. Number of Subjects With Treatment Emergent Adverse Events Related to Pembrolizumab as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

    Safety evaluation: number of subjects with treatment emergent adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. This is an assessment of the frequency and relationship to trial treatment of all adverse events that occurred while on trial. CTCAE is a standard classification and severity grading scale (from 1- mild to 5 - death) for adverse events in clinical trials and oncology settings.

    Measured: The average time period for patient participation was 30 weeks.

Timeline

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

  1. First posted14 Sep 2016 (estimated)
  2. Study start20 Dec 2016
  3. Primary completion27 May 2021
  4. Study completion27 May 2021

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
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02900560
Sponsor's protocol ID
TRIO026
Status last verified
May 2022
First submitted
1 Sep 2016
Last updated
10 Jun 2022
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CC-486 and Pembrolizumab in people with Epithelial Ovarian Cancer, run by Translational Research in Oncology at 4 sites 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 24 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: stopped early, as of the sponsor's last update on 10 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 10 Jun 2022). 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?

Number of Subjects With Grade 3, 4, or 5 Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.03 (time frame: The average time period for patient participation was 30 weeks.). The study lists 4 primary outcomes in all. 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 10 Jun 2022.

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