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HER2-Negative Metastatic Breast CancerPhase 1NCT03430518

Durvalumab and Eribulin in Her2-negative Metastatic Breast Cancer and Recurrent Ovarian Cancer

A Phase 1 study testing Durvalumab and Eribulin in people with HER2-Negative Metastatic Breast Cancer and Recurrent Ovarian Cancer, run by Amy Tiersten at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will evaluate the recommended Phase 2 combination dose (RP2D) of eribulin with durvalumab. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Durvalumab and Eribulin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
17 May 2018to 10 Feb 2020
Phase
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

  • Written informed consent and HIPAA authorization obtained from the subject and documented according to local regulatory requirements prior to beginning any protocol-specific procedures, including screening procedures
  • The subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations, including all follow-up
  • The subject is medically fit for protocol therapy and competent to give informed consent
  • The subject must have a performance status of 0-1 as determined by criteria set forward by ECOG
  • Subjects with histologically confirmed stage IV any hormone receptor (HR) status/HER2 negative breast cancer or advanced/recurrent epithelial ovarian cancer
  • HR positive, HER2 negative breast cancer: patients must have received at least one line of therapy for metastatic disease prior to enrollment, including hormonal therapy and a CDK4/6 inhibitor
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  • HR negative, HER2 negative breast cancer: patients must have received at least one prior line of chemotherapy for metastatic disease
  • Recurrent, "platinum-sensitive" epithelial ovarian cancer: patients must have received at least two lines of platinum-based chemotherapy prior to enrollment, with at least one of these lines of platinum-based chemotherapy in the recurrent setting
  • Recurrent, "platinum-resistant" (recurrence within 6 months of a platinum-containing chemotherapy regimen) epithelial ovarian cancer: patients must have received at least one line of platinum-based chemotherapy prior to enrollment
  • There is pathologic tissue confirming of metastatic breast or ovarian cancer
  • All adverse events from prior chemotherapy, radiation, or surgery have either returned to baseline or are < grade 1 prior to administration of the investigational product
  • The subject has a body weight of greater than 30kg
  • The subject must have at the time of screening acceptable hematologic, hepatic, and renal function, defined by the following (≤ 28 days prior to registration):
  • Absolute neutrophil count > 1500/mm3
  • Hemoglobin > 10g/dL
  • Platelet count > 100,000/mm3
  • Creatinine < 1.6 mg/dL
  • Serum creatinine clearance >40mL/min by the Cockcroft-Gault formula or by 24-hour urine collection
  • Serum bilirubin < 1.5x the upper limit of institutional normal, excluding patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology)
  • Transaminases (AST/SGOT and ALT/SGPT) < 2.5 times above the upper limits of the institutional normal, unless liver metastases are present, in which case it must be < 5x ULN
  • INR < 2 for patients who are not on systemic anticoagulation. Patients on anticoagulation therapy with an INR > 2 may be enrolled at the discretion of the investigator if they have not had any episodes of severe hemorrhage or active bleeding
  • The subject must be 18 years of age or older
  • The subject must have not had more than 5 prior lines of cytotoxic chemotherapy in the metastatic setting, not including hormonal therapies
  • Evidence of post-menopausal status, history of hysterectomy or bilateral oophorectomy, or negative serum or urine pregnancy test within 7 days prior to starting treatment
  • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have LH and FSH levels in the post-menopausal range for the institution
  • Women > 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, or had chemotherapy-induced menopause with last menses >1 year ago
  • Women of child-bearing potential must agree to use at least one highly effective form of contraception beginning at least 28 days prior to study entry, continuing to do so for the duration of their participation in the study, and for 90 days after the last dose of study drug. Non-sterilized male partners must also agree to use a male condom plus spermicide for the duration of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • A female of childbearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months without alternative medical cause), as defined above in section 3.1.1

Who cannot join

  • Prior treatment with any investigational drug as part of a clinical trial within 28 days prior to study drug administration
  • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
  • The subject has been treated previously with any anti-PD1/PDL1 therapy, including durvalumab
  • The subject has been previously treated with eribulin
  • The subject has received a prior anti-cancer therapy (chemotherapy, targeted small molecule therapy, endocrine therapy, immunotherapy, biologic therapy, tumor embolization, monoclonal antibodies) within 14 days prior to study Day 1
  • Any concurrent anti-cancer therapy other than denosumab, bisphosphonates, or hormonal therapy for non-cancer related conditions
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  • The subject has received radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 28 days of the first dose of study drug
  • Major surgical procedure within 28 days prior to the first dose of study drug (local surgery or isolated lesions for palliative intent is acceptable)
  • Any unresolved toxicity NCI CTCAE Grade >2 from previous anticancer therapy with the exception of alopecia, vitiligo, and lab values which meet inclusion criteria
  • Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study as per consultation with the study physician. These patients will require active and continuous monitoring of this toxicity and if any worsening is observed or identified, study drugs will be permanently discontinued immediately
  • Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with eribulin or durvalumab may be included after consultation with the study physician
  • The subject has a history of, or is reasonably suspected to meet criteria for the diagnosis of a known congenital or acquired disorder causing systemic immunosuppression or immunodeficiency
  • The subject has a history of allogeneic organ or bone marrow transplantation
  • The subject has a history of, or is reasonably suspected to meet criteria for the diagnosis of a systemic auto-immune/inflammatory disease or other autoimmune disorder, including but not limited to inflammatory bowel disease (Crohn's disease or ulcerative colitis), active diverticulitis, systemic lupus erythematosus, Sarcoidosis, Wegener's granulomatosis, granulomatosis with polyangiitis, pneumonitis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis.
  • Exceptions: vitiligo, alopecia, autoimmune-related hypothyroidism which is stable on hormone replacement, chronic skin conditions that do not require systemic therapy, celiac disease controlled with diet alone, or any subjects without active disease in the last 5 years if deemed appropriate by the study physician
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exception of inhaled, local injection, or intranasal corticosteroids, systemic steroids at physiological doses (equivalent of ≤ 10mg prednisone daily), and steroid premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • The subject has known active central nervous system (CNS) metastases, spinal cord compression, and/or leptomeningeal carcinomatosis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 28 days prior to the first dose of trial treatment 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 trial treatment. Following radiotherapy and/or surgery for brain metastases subjects must wait 4 weeks following the intervention before enrollment to confirm stability.
  • The subject has a current or past history of active TB (Bacillus Tuberculosis)
  • The subject has an active infection requiring systemic therapy
  • The subject has HIV disease (positive HIV 1/2 antibodies)
  • The subject has active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] PCR is detected). Subjects with a past or resolved HBV infection (HBcAb positive and absence of HBsAg reactivity) are eligible
  • The subject has received a live virus 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.
  • The subject has a known additional malignancy that is progressing or requires active treatment. Exceptions include non-melanoma cancers of the skin that have been resected, in situ malignancies that have been managed with curative therapy and there is no current evidence of disease at time of trial enrollment, or history of prior malignancy with no known active disease for 5 years prior to trial enrollment
  • Female patients who are pregnant or breast feeding
  • Subject is of reproductive potential and is not willing to use effective birth control methods from screening for 90 days after the last dose of durvalumab
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab or eribulin
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study including but not limited to:
  • Symptomatic congestive heart failure of New York Heart Association Class III or IV
  • Mean QT interval corrected for heart rate (QTc) > 470ms calculated from 3 electrocardiograms within 15 minutes at 5 minutes apart using Fridericia's Correction
  • Unstable angina pectoris, uncontrolled hypertension, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
  • Interstitial lung disease, or severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 89% or less at rest on room air
  • Serious chronic gastrointestinal conditions associated with diarrhea
  • A known or active bleeding diathesis
  • Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial or increase risk of adverse events
  • Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN
  • Active (acute or chronic) or uncontrolled infections
  • Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

About this study

Official title: A Phase Ib Study Evaluating the Safety and Tolerability of Durvalumab (MEDI4736) (Anti-PDL1) in Combination With Eribulin in Patients With HER2-Negative Metastatic Breast Cancer and Recurrent Ovarian Cancer

This study will evaluate the recommended Phase 2 combination dose (RP2D) of eribulin with durvalumab.

Read the detailed description

STUDY SUMMARY

Study Duration: Accrual will take place over the course of 16 months. Patients will be treated until unacceptable toxicity or disease progression (expected on average for 6 months) and then followed for one year thereafter.

Objectives: Phase I: To determine the the recommended phase II dose of eribulin in combination with Durvalumab

This study will evaluate the recommended Phase 2 combination dose (RP2D) of eribulin with durvalumab. If two or more out of 6 patients experience a dose limiting toxicity (DLT) at dose level I or II, the dose level below that level will be considered the RP2D. If all 3 patients enter dose level-I and experience DLT, the study will be terminated. If the highest level has been reached and < 33% of patients have experienced DLT, that will be considered the RP2D.

Being tested
Durvalumab, Eribulin
Keywords
Durvalumab (MEDI4736) (Anti-PDL1), Eribulin, Recurrent Ovarian cancer, Her2-negative Metastatic Breast Cancer, Ovarian cancer, Metastatic Breast Cancer
Medical subject headings
Ovarian Neoplasms, Breast Neoplasms

What participants receive

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

  • DurvalumabDrug

    1.12g given IV on day 1 every 21 day cycle

  • EribulinDrug

    1.1 mg/m2 IV on day 8 of every 21 day cycle in the first 3 patients, then increased to 1.4mg/m2 IV on day 1 and day 8 of every 21 day cycle. If significant toxicity occurs in patients given the 1.1mg/m2 IV dose, then subsequent patients with receive eribulin 0.7mg/m2 IV on day 1 and day 8 of every 21 day cycle.

Study groups in NCT03430518
Study groupRoleWhat they receive
Her2-negative Metastatic Breast Ca and Recurrent Ovarian CaExperimentalDurvalumab and Eribulin in Her2-negative Metastatic Breast Cancer and Recurrent Ovarian cancer
Receives: Drug: Durvalumab; Drug: Eribulin

What is being measured

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

  1. The dose-limiting toxicity (DLT) rate

    A DLT is defined as a ≥ Grade 3 or 4 study drug-related adverse event (using NCI CTCAE Version 4.03) that occurs during the DLT evaluation period. Toxicity that is clearly and directly related to the primary disease or to another etiology is excluded from this definition.

    Measured: 42 days

Secondary outcomes (5)

  1. Number of Adverse events

    Adverse events associated with eribulin when administered in combination with durvalumab will be described according to the Medical Dictionary for Regulatory Activities (MedDRA) by system organ classes.

    Measured: 6 months

  2. Objective response rate (ORR)

    Objective response rate (ORR) is measured as the proportion of patients who have achieved complete response, partial response (CR, PR) according to Immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) criteria. irCR, complete disappearance of all measurable and non-measurable lesions. Lymph nodes must decrease to < 10 mm in short axis. Confirmation of response is not mandatory. irPR, decrease of ≥ 30% in TMTB relative to baseline, non-target lesions are irNN, and no unequivocal progression of new non-measurable lesions.

    Measured: 6 months

  3. Progression free survival (PFS)

    Progression free survival (PFS) is measured from the start of first treatment until the criteria for progression are met or death, whichever occurs earlier. Patients without documented progression/death will be censored at the last disease assessment date.

    Measured: 16 months

  4. Overall survival (OS)

    Overall survival (OS) is measured from the start of first treatment until death due to any cause. Patients without documented death at the time of analysis will be censored at the date last known to be alive.

    Measured: 6 months

  5. ECOG performance status

    Eastern Cooperative Oncology Group (ECOG) performance status. Grade 0: Fully active, able to carry on all pre-disease performance without restriction Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work Grade 2: Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours Grade 4: Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair Grade 5: Dead

    Measured: 6 months

Timeline

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

  1. First posted13 Feb 2018
  2. Study start17 May 2018
  3. Primary completion10 Feb 2020
  4. Study completion10 Feb 2020

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03430518
Sponsor's protocol ID
GCO 17-2320
Status last verified
Aug 2020
First submitted
6 Feb 2018
Last updated
5 Aug 2020
Results posted
No
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 study testing Durvalumab and Eribulin in people with HER2-Negative Metastatic Breast Cancer and Recurrent Ovarian Cancer, run by Amy Tiersten 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 30 inclusion and 37 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 5 Aug 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?

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.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

The dose-limiting toxicity (DLT) rate (time frame: 42 days). 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 NCT03430518.

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 5 Aug 2020.

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