Overview

A Phase II Study of Neoadjuvant Chemotherapy Plus Durvalumab (MEDI4736) and Tremelimumab in Advanced-stage Ovarian Cancer (TRU-D)

Status:
Recruiting
Trial end date:
2021-05-01
Target enrollment:
0
Participant gender:
Female
Summary
The primary objective of this trial is to evaluate the synergistic effects of durvalumab and tremelimumab plus chemotherapy in advanced-stage ovarian cancer. Ovarian cancer is the deadliest gynecologic cancer. The current standard therapy is surgical cytoreduction followed by taxane-platinum combination chemotherapy. However, most patients with advanced-stage ovarian cancer will experience a relapse of disease. Therefore, there is an urgent need to improve outcomes of patients with this aggressive cancer. Research hypothesis: Adding durvalumab and tremelimumab to current neoadjuvant chemotherapy (front-line therapy) in advanced-stage ovarian cancer can increase response rate and improve patient's outcome such as progression-free survival and overall survival with minimal effects on safety.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Yonsei University
Collaborators:
AstraZeneca
Korean Gynecologic Oncology Group
National Cancer Center, Korea
Samsung Genomic Institute
Samsung Medical Center
Seoul National University Hospital
Treatments:
Antibodies, Monoclonal
Carboplatin
Durvalumab
Paclitaxel
Tremelimumab
Criteria
Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of ovary, fallopian tube, primary peritoneum

2. Clinical stage IIIC/IV

3. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol. Written informed consent and any locally required authorization (eg, Health
Insurance Portability and Accountability Act in the US, European Union [EU] Data
Privacy Directive in the EU) obtained from the patient/legal representative prior to
performing any protocol-related procedures, including screening evaluations.

4. Female aged 20 years older at the time of acquisition of informed consent

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 ~ 1

6. Must have life expectancy of at least 16 weeks

7. Body weight >30kg

8. Adequate normal organ and marrow function as defined below:

- Haemoglobin ≥9.0 g/dL

- Absolute neutrophil count (ANC) ≥1.5 x 109/L

- Platelet count ≥100 x 109/L

- Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). < apply to patients with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis
or hepatic pathology), who will be allowed only in consultation with their
physician.>>

- AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver
metastases are present, in which case it must be ≤5x ULN

- Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine clearance
CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by
24-hour urine collection for determination of creatinine clearance:

Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine
(mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum
creatinine (mg/dL)

9. Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal patients. Women will be considered post-menopausal if they have
been amenorrheic for 12 months without an alternative medical cause. The following
age-specific requirements apply:

- 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 luteinizing hormone and follicle-stimulating hormone
levels in the post-menopausal range for the institution or underwent surgical
sterilization (bilateral oophorectomy or hysterectomy).

- Women ≥50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced menopause with last menses >1 year ago, had
chemotherapy-induced menopause with last menses >1 year ago, or underwent
surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
hysterectomy).

10. Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up.

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site)

2. Participation in another clinical study with an investigational product during the
last 60 days

3. 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

4. Any previous treatment with anti-PD-1, PD-L1, CTLA-4 (including durvalumab and
tremelimumab)

5. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria

- Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after
consultation with the Study Physician.

- Patients with irreversible toxicity not reasonably expected to be exacerbated by
treatment with durvalumab or tremelimumab may be included only after consultation
with the Study Physician.

6. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone
replacement therapy) is acceptable. < studies with other anticancer agents>>

7. Major surgical procedure (except diagnostic laparoscopy) within 28 days prior to the
first dose of IP. Note: Local surgery of isolated lesions for palliative intent is
acceptable.

8. History of allogenic organ transplantation.

9. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,
or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this
criterion:

- Patients with vitiligo or alopecia

- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement

- Any chronic skin condition that does not require systemic therapy

- Patients without active disease in the last 5 years may be included but only
after consultation with the study physician

- Patients with celiac disease controlled by diet alone

10. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
situations that would limit compliance with study requirement, substantially increase
risk of incurring AEs or compromise the ability of the patient to give written
informed consent

11. Other malignancy within the last 5 years except: adequately treated non-melanoma skin
cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ
(DCIS), Stage 1, grade 1/2 endometrial carcinoma, or other solid tumours including
lymphomas (without bone marrow involvement) curatively treated with no evidence of
disease for ≥5 years. Patients with a history of localised breast cancer may be
eligible, provided they completed their adjuvant chemotherapy more than two years
prior to registration, and that the patient remains free of recurrent or metastatic
disease

12. History of leptomeningeal carcinomatosis

13. Brain metastases or spinal cord compression. Patients with suspected brain metastases
at screening should have an MRI (preferred) or CT each preferably with IV contrast of
the brain prior to study entry

14. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms
calculated from 3 ECGs (within 15 minutes at 5 minutes apart) << For durvalumab
±tremelimumab in combination with an agent with pro-arrhythmic potential or where
effect of the combination on QT is not known if this criterion should be retained.
Patient safety and the cardiac EKG should be consulted as needed>>.

15. History of active primary immunodeficiency