DOVACCA study investigating the effect of the medication: olaparib, durvalumb and UV1 as maintenance therapy for patients with Recurrent Ovarian Cancer

Phase 1

• Conditions: Ovarian cancer; MedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-004738-39-AT
• Lead Sponsor: ordic Society of Gynaecological Oncology - Clinical Trial Unit

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-02-01
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 184

Inclusion Criteria

1. 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. The consent must be signed before the time of inclusion.
2. Histologically diagnosed epithelial ovarian, fallopian tube or primary peritoneal cancer, excluding mucinous or low-grade serous histology
3. Radiological or histological confirmation of relapse disease = 6 month after after penultimate chemotherapy.
4. Patients who are non-gBRCAmutn or tBRCAwt
5.Have completed at least two lines, but no more than 3 lines, of chemotherapy, which means that patients at first or second relapse with treatment free interval of more than 6 months on penultimate chemotherapy are eligible.
a. Patients must have completed at least 4 cycles of the latest platinum-containing chemotherapy.
6. Be either:
a. PARPi naive
b. Earlier treated with PARPi and not progressed during 6 months of PARPi therapy
7. Must not, in the opinion of the investigator, have progressed on, or after, latest platinumcontaining chemotherapy. This means that patients with CR, PR, SD or no evidence of disease (NED) are eligible. It should be documented on the post-treatment scan following completion of the last chemotherapy course.
8. Patient consents to HRD test *(Acceptable HRD tests: Myriad myChoice® CDx, Leuven HRD test, NOGGO GISv1, and TSO 500 HRD).
9. Must be included in the study within 10 weeks of completion of the final dose of platinum-containing chemotherapy.
10. Age =18 years
11. Body weight > 30 kg
12. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix 3)
13. Must have a life expectancy = 16 weeks.
14. Must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
- Haemoglobin = 10.0 g/dL (6,2 mmol/L) with no blood transfusion in the past 28 days
- Absolute neutrophil count (ANC) = 1.5 x 10^9/L
- Platelet count = 100 x 10^9/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 institutional upper limit of normal unless liver metastases are present in which case, they must be = 5x ULN
- Must have creatinine clearance estimated of = 51 mL/min using the Cockcroft-Gault equation or based on a urine test:
o Estimated creatinine clearance = [[140 - age(yr)] x weight(kg)] / [72 x serum Cr (mg/dL)] (multiply by 0.85 for women)
15. Ability to swallow oral medications (tablets) without chewing, breaking, crushing, opening or otherwise altering the product formulation.
16. Post-menopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.
Post-menopausal is defined as:
- Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments
- Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50
- radiation-induced oophorectomy with last menses > 1 year ago
- chemotherapy-induced menopause with > 1year interval since last menses
- surgical sterilisation (bilateral oophorectomy 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 Num

Exclusion Criteria

1. Previous use of immune checkpoint inhibitors.
a. In case the patient has participated in an immune checkpoint inhibitor blinded study, the patient may be enrolled without unblinding.
2. Other malignancy unless curatively treated with no evidence of disease for = 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 endometrial carcinoma.
3. Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator, or patients with congenital long QT syndrome.
4. Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
5. Patients with symptomatic uncontrolled brain metastases.
6. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection.
7. Concomitant treatment with bevacizumab within the last 3 weeks.
8. Concomitant therapy with any other anticancer therapy or chronic use of systemic corticosteroids of more than 10 mg prednisolone daily.
9. Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks.
10. Concomitant use of known strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or
phenobarbital and 3 weeks for other agents.
11. Previous allogeneic bone marrow transplant or double umbilical cord blood transplantation.
12. Major surgery or significant traumatic injury within 28 days of randomization.
13. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV), patients with active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
14. Pregnancy, lactation, or intention to become pregnant during the study or/and within 1 month after the last dose of olaparib. If the patient can become pregnant, the patient must be on acceptable birth control listed in Appendix 5.
15. Participation in a clinical study within 28 days or 5 half-lives of the drug, whichever is longest.
16. Patients unable to swallow orally administered medication or patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
17. Patients with a history of allergy or hypersensitivity to any of the study drugs
18. Any unresolved toxicity NCI CTCAE Grade = 2 from previous anticancer therapy except for alopecia, vitiligo, and the laboratory values defined in the inclusion criteria:
a. Patients with Grade = 2

Study & Design

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