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

NCT02900560 | Terminated Phase 2 Results

• 1 other identifier: TRIO026
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 4

Brief 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).

Conditions

Epithelial Ovarian Cancer

Outcome Measures

Primary Outcomes (4)

• 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.

  The average time period for patient participation was 30 weeks.

• 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.

  The average time period for patient participation was 30 weeks.

• 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.

  The average time period for patient participation was 30 weeks.

• 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.

  The average time period for patient participation was 30 weeks.

Study Arms (4)

Cohort 1

ACTIVE COMPARATOR

CC-486 100 mg once a day, 21 days on, 7 days off combined with Pembrolizumab 200 mg IV every 21 days

Drug: CC-486; Biological: Pembrolizumab

Cohort 2

ACTIVE COMPARATOR

CC-486 100 mg twice a day, 21 days on, 7 days off combined with Pembrolizumab 200 mg IV every 21 days

Drug: CC-486; Biological: Pembrolizumab

Cohort 3

ACTIVE COMPARATOR

CC-486 300 mg once a day, 14 days on and 14 days off combined with Pembrolizumab 200 mg IV every 21 days

Drug: CC-486; Biological: Pembrolizumab

Cohort 4

ACTIVE COMPARATOR

CC-486 300 mg once a day, 21 days on, 7 days off combined with Pembrolizumab 200 mg IV every 21 days

Drug: CC-486; Biological: Pembrolizumab

Interventions

CC-486 DRUG

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

Also known as: oral azacitidine

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Pembrolizumab BIOLOGICAL

Pembrolizumab 200 mg IV every 21 days

Also known as: Keytruda

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Translational Research in Oncology: lead
• Celgene: collaborator

Study Sites (4)

UCLA

Los Angeles, California, 90095, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial

Interventions

cc-486; Azacitidine; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Limitations and Caveats

Trial closed prematurely with 34 participant enrolled in Part A of the study. All of the treatment cohorts met at least one of the safety rejection criteria. Enrollment took 31 months, significantly longer than anticipated (24 months).

Results Point of Contact

• Title: Director, Project Management
• Organization: Translational Research In Oncology (TRIO)

026@trioncology.org

33 158 10 09 09

Study Officials

• Rodrigo Fresco, MD

  Translational Research in Oncology

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2016
• First Posted: September 14, 2016
• Study Start: December 20, 2016
• Primary Completion: May 27, 2021
• Study Completion: May 27, 2021
• Last Updated: June 10, 2022
• Results First Posted: June 10, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)