DOMEC - phase II trial of Durvalumab and Olaparib in advanced Endometrial Cancer.

Phase 1

• Conditions: advanced endometrial cancer; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-004575-12-NL
• Lead Sponsor: eiden University Medical Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-07-08
• Last Update Posted: 11 January 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 55

Inclusion Criteria

1. Must provide written informed consent prior to performance of study-specific procedures or
assessments, and must be willing to comply with treatment and follow-up assessments.
2. Age > 18 years old
3. Histologically or cytologically confirmed diagnosis of endometrial cancer or carcinosarcoma of the endometrium. Besides central revision, a tumor block or 20 slides are asked for TR.
4. Metastatic disease or locally advanced tumor not amenable to local therapy.
5. Documented progressive disease before enrolment.
6. Measurable lesions outside irradiated field or progressive measurable lesions in irradiated area
7. Not eligible for hormonal therapy (because of negative hormone receptor/poor differentiation, or after failure of hormonal therapy).
8. Previous failure of chemotherapy, or refusal to undergo chemotherapy or chemo-naive patients not suitable for chemotherapy.
9. WHO performance 0-1
10. Adequate organ system function as measured within 28 days prior to administration of study treatment, as defined below:
? Haemoglobin = 10.0 g/dL, with no blood transfusion in the past 28 days.
? Absolute neutrophil count (ANC) = 1.5 x 109/L
? Platelet count = 100 x 109/L
? Total bilirubin = 1.5 x institutional upper limit of normal (ULN)
? Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) = 2.5 x ULN unless liver metastases are present in which case they must be = 5x ULN
? Patients must have creatinine clearance estimated of =51 mL/min estimated using the Cockcroft-Gault equation or 24 hr urine clearance :
11. Expected adequacy of follow-up
12. Life expectancy of at least 16 weeks.
13. Measurable disease as defined by RECIST 1.1 criteria
14. Able to swallow and retain oral medication.
15. Body weight > 30 kg
16. A female is eligible to enter and participate in this study if there is:
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 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).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

1. another investigational product during the last month.
2. Any previous treatment with PARP inhibitor and/or any previous treatment with a PD1 or PD-L1 inhibitor.
3. History of another primary malignancy that could conceivably be active evaluated by the study physician.
4. History of leptomeningeal carcinomatosis. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids (maximum 2 mg/day) before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
5. Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
6. Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors. The required washout period prior to starting olaparib is 2 weeks.
7. Concomitant use of known strong or moderate CYP3A inducers. The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
8. 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 and olaparib may be included only after consultation with the Study Physician.
9. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
10. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
11. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
12. History of active primary immunodeficiency
13. Active or prior documented autoimmune or inflammatory disorders, 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 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
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Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified