AzTrials
AzTrials

Platinum-resistant Ovarian CancerPhase 1/2SEASCAPENCT02575807

Safety and Efficacy of CRS-207 With Epacadostat in Platinum Resistant Ovarian, Fallopian or Peritoneal Cancer

A Phase 1/2 study testing CRS-207, Epacadostat and Pembrolizumab in people with Platinum-resistant Ovarian Cancer and Platinum-resistant Fallopian Cancer, run by Aduro Biotech, Inc. at 12 sites in 2 countries.

Terminated

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

Official record
Search all trials

Trial summary

This 2-part, Phase 1/2 study will test investigational cancer drugs known as CRS-207, epacadostat (IDO), and pembrolizumab (pembro). The purpose of this study is to find out how safe it is to give the investigational drugs to women with platinum-resistant ovarian, fallopian tube, or peritoneal cancer and if it helps… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
CRS-207, Epacadostat and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
12 sitesin 2 countries
Study dates
8 Mar 2016to 8 May 2018
Phase
Phase 1/2
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

  • Histologically-confirmed disease
  • Phase 1: Individuals with epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinomas who are considered to have platinum-resistant disease (progression within 6 months from completion of platinum-based chemotherapy).
  • Phase 2: Individuals with epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinomas who are considered to have platinum-resistant disease (progression within 6 months from completion of a minimum of 4 platinum therapy cycles).
  • Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • Agree to provide core biopsies at baseline and at Cycle 2 Day 15
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Available archived tumor tissue for central analysis
  • Adequate organ and marrow function

Who cannot join

  • Platinum-refractory disease (progression during the first platinum-based chemotherapy)
  • Major surgical procedure within 4 weeks prior to Study Day 1
  • Inaccessible tumors or for whom biopsy is contraindicated
  • Clinically significant ascites
  • Phase 2 only: Previous treatment with >3 chemotherapy regimens for locally advanced or metastatic disease
  • Active bowel obstruction, or hospitalization for bowel obstruction within 2 months prior to screening
Show all 23Show fewer
  • Require parenteral nutrition
  • Hospitalization within 2 weeks prior to screening
  • Received any anticancer medication or therapy in the 21 days prior to study Day 1
  • Prior monoclonal antibody treatment within 4 weeks before study Day 1
  • History of listeriosis or previous treatment with a listeria-based immunotherapy
  • Known allergy to both penicillin and sulfa antibiotics
  • Any immunodeficiency disease or immune-compromised state
  • Received prior immune checkpoint inhibitors (e.g., anti-CTLA-4, anti-PD-1, anti PDL-1) and any other antibody or drug specifically targeting T-cell costimulation or an IDO inhibitor
  • Pregnant or breastfeeding
  • Clinically significant heart disease
  • Valvular heart disease that requires antibiotic prophylaxis for prevention of endocarditis
  • History of any autoimmune disease which required systemic therapy in the past 2 years
  • Diagnosed with another malignancy within the past 3 years
  • Currently receiving therapy with a UDP-glucuronosyltransferase 1A9 inhibitor including diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid
  • Receiving monoamine oxidase inhibitor (MAOIs) or a drug which has significant MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before screening
  • Had prior serotonin syndrome
  • Has implanted medical devices that pose high risks for colonization and cannot be easily removed

Trial locations and contacts

12 sites in 2 countries.

12 sites in 2 countries

United States10 sites

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • University of Virginia Health System

    Charlottesville, Virginia, 22903

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Florida

    Gainesville, Florida, 32610

  • University of Pennsylvania Health System

    Philadelphia, Pennsylvania, 19104

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Scottsdale Healthcare Hospitals DBA HonorHealth

    Scottsdale, Arizona, 85258

  • Virginia Mason Medical Center

    Seattle, Washington, 98101

  • Stanford Cancer Center

    Stanford, California, 94305

Other trials in United States

Canada2 sites

  • CHUM - Centre Hospitalier de l'Université de Montréal

    Montreal, Quebec, H2X 0A9

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase 1/2, Open-Label Safety and Efficacy Evaluation of CRS-207 in Combination With Epacadostat in Adults With Platinum-Resistant Ovarian, Fallopian, or Peritoneal Cancer

This 2-part, Phase 1/2 study will test investigational cancer drugs known as CRS-207, epacadostat (IDO), and pembrolizumab (pembro). The purpose of this study is to find out how safe it is to give the investigational drugs to women with platinum-resistant ovarian, fallopian tube, or peritoneal cancer and if it helps patients with these types of cancer live longer or can help shrink or slow the growth of cancer.

Being tested
CRS-207, Epacadostat, Pembrolizumab
Keywords
Ovarian cancer, Fallopian cancer, Primary peritoneal cancer
Medical subject headings
Ovarian Neoplasms

What participants receive

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

  • CRS-207Biological

    Also called Live, attenuated double-deleted Listeria monocytogenes (LADD)

    via IV infusion

  • EpacadostatDrug

    Also called INCB024360, IDO

    PO BID

  • PembrolizumabBiological

    Also called Keytruda®, Pembro

    via IV infusion

Study groups in NCT02575807
Study groupRoleWhat they receive
Phase 1: CRS-207ExperimentalCRS-207 administered in 3-week cycles. * CRS-207 (1 x 10e9 colony forming units [CFU]) administered by intravenous (IV) infusion. For Cycle 1 through Cycle 6, CRS-207 will be administered on Day 1 of each cycle. After 6 cycles, CRS-207 will be administered on Day 1 once every 6 weeks (every other cycle).
Receives: Biological: CRS-207
Phase 1: CRS-207/IDO 100 mgExperimentalCRS-207 administered in 3-week cycles, IDO administered twice daily (BID). * CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). * IDO (100 milligrams [mg]) administered by mouth (PO) BID, starting on Day 2 of the first CRS-207 treatment cycle.
Receives: Biological: CRS-207; Drug: Epacadostat
Phase 1: CRS-207/IDO 300 mgExperimentalCRS-207 administered in 3-week cycles, IDO administered BID. * CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). * IDO (300 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.
Receives: Biological: CRS-207; Drug: Epacadostat
Phase 2: CRS-207/Pembro/IDOExperimentalCRS-207 and pembrolizumab (pembro) administered in 3-week cycles, IDO administered BID. * CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). * Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles. * IDO (300 mg) administered PO BID, starting on Day 3 of the first CRS-207 treatment cycle.
Receives: Biological: CRS-207; Drug: Epacadostat; Biological: Pembrolizumab
Phase 2: CRS-207/PembroExperimentalCRS-207 and pembro administered in 3-week cycles. * CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). * Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles.
Receives: Biological: CRS-207; Biological: Pembrolizumab

What is being measured

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

  1. Phase 1: Number of Subjects Reporting Hematologic and/or Non-hematologic Dose-limiting Toxicity (DLT)

    Count of subjects in the Phase 1 cohorts who reported a hematologic and/or non-hematologic DLT. Non-hematological DLTs are defined as follows, excluding the safety events specified for exemption in Section 5.3.1 of the study protocol:

    • any treatment-emergent adverse event (TEAE) not attributable to disease or disease-related processes that occurs during the DLT observation period (Cycle 1) and is Grade 3 or higher according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4;
    • any use of systemic steroids; and/or
    • a study drug dose interruption lasting ≥ 7 days for an adverse event with an unclear relationship to study drug.

    Hematological DLTs are defined as:

    • Grade 4 neutropenia lasting >7 days;
    • Grade ≥3 febrile neutropenia;
    • Grade 4 anemia;
    • Grade 4 thrombocytopenia or ≥ Grade 3 thrombocytopenia lasting >7 days or associated with bleeding; and/or
    • Dose delay >7 days secondary to myelosuppression.

    Measured: Subjects followed for DLTs for 21 days following the first dose of CRS-207 (treatment Cycle 1 for CRS-207).

  2. Phase 1: Adverse Events (AEs) by CTCAE Grade 3 or Higher

    Count of subjects in the Phase 1 cohorts with incidences of CTCAE Grade 3 or higher AEs.

    Measured: Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 3 months.

  3. Phase 2: Adverse Events (AEs)

    Count of subjects in the Phase 2 cohorts with incidences of AEs.

    Measured: Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 2 months.

  4. Phase 2: Objective Response Rate (ORR)

    ORR was evaluated for Phase 2 subjects based upon the best overall response (BOR) for individual study subjects. BOR was determined by the highest post-baseline qualitative response value for each assessed subject as measured by modified response evaluation criteria in solid tumors (mRECIST) and given the following hierarchy of overall response results: complete response (CR) > partial response (PR) > stable disease (SD) > progressive disease (PD) > not evaluable (NE). The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP). Therefore, the number of evaluable subjects with BOR mRECIST values of CR, PR, SD, PD, and NE are provided for this outcome measure.

    Measured: BOR was assessed from the first dose of study treatment until documented disease progression, initiation of a new cancer treatment, death, or study termination, whichever comes first, assessed up to 20 weeks.

  5. Phase 2: Progression Free Survival (PFS)

    Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) or death from any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). PD is determined by mRECIST.

    Measured: Subjects followed for disease progression from first dose of study treatment until 30 days after last dose of study treatment or initiation of new cancer treatment, whichever comes first, assessed up to 20 weeks.

Secondary outcomes (5)

  1. Phase 1: Objective Response Rate (ORR) by mRECIST

    ORR was evaluated for Phase 1 subjects based upon the best overall response (BOR) for individual study subjects. BOR was determined by the highest post-baseline qualitative response value for each assessed subject as measured by modified response evaluation criteria in solid tumors (mRECIST), RECIST v1.1, and GCIG CA-125 criteria and given the following hierarchy of overall response results: complete response (CR) > partial response (PR) > stable disease (SD) > progressive disease (PD) > not evaluable (NE). The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP). Therefore, the number of evaluable subjects with BOR mRECIST values of CR, PR, SD, PD, and NE are provided for this outcome measure.

    Measured: BOR was assessed from the first dose of study treatment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 100 weeks.

  2. Phase 1: Progression Free Survival (PFS)

    Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) or death due to any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). PD is determined by mRECIST, RECIST v1.1, and GCIG CA-125.

    Measured: Subjects followed for disease progression from first dose of study treatment until 30 days after last dose of study treatment or initiation of new cancer treatment, whichever comes first, assessed up to 100 weeks

  3. Disease Control Rate (DCR)

    The protocol-specified DCR was defined as the percentage of evaluable subjects with a BOR of CR or PR, or SD as determined by mRECIST, RECIST v1.1, and GCIG CA-125 criteria.

    Measured: BOR was assessed from the first dose of study treatment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever comes first, assessed up to 100 weeks.

  4. Duration of Response (DOR)

    Number of weeks from date of CR or PR designation until PD designation, as determined by mRECIST, RECIST v1.1 and GCIG CA-125 criteria.

    Measured: Subjects followed for disease progression from date of CR or PR designation until documented disease progression or study termination, whichever comes first, assessed up to 100 weeks.

  5. Overall Survival (OS)

    Number of weeks from the date of first dose of study treatment to the date of death from any cause, estimated using KM methods with 95% CIs for subjects in the SAF. Subjects without documentation of death at the time of analysis were censored as of the date the subject was last known to be alive. For subjects lost to follow up, the last visit or last contact date where the subject is documented to be alive will be used to estimate last known date alive.

    Measured: OS was assessed from the first dose of study treatment until death or study termination, whichever comes first, assessed up to 100 weeks.

Timeline

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

  1. First posted15 Oct 2015 (estimated)
  2. Study start8 Mar 2016
  3. Primary completion26 Apr 2018
  4. Study completion8 May 2018

Why it stopped: Study was stopped due to low enrollment and lack of clinical activity.

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02575807
Sponsor's protocol ID
ADU-CL-11
Acronym
SEASCAPE
Status last verified
Apr 2019
First submitted
12 Oct 2015
Last updated
4 Apr 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CRS-207, Epacadostat and Pembrolizumab in people with Platinum-resistant Ovarian Cancer and Platinum-resistant Fallopian Cancer, run by Aduro Biotech, Inc. at 12 sites in 2 countries.

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 8 inclusion and 23 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 4 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States, Canada. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 4 Apr 2019). 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?

Phase 1: Number of Subjects Reporting Hematologic and/or Non-hematologic Dose-limiting Toxicity (DLT) (time frame: Subjects followed for DLTs for 21 days following the first dose of CRS-207 (treatment Cycle 1 for CRS-207).). The study lists 5 primary outcomes in all. 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 NCT02575807.

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 4 Apr 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in