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New treatment option for Epithelial Ovarian Cancer
Official title WoO: Window of Opportunity Trial of Olaparib and Durvalumab in Histologically Proven EOC
ClinicalTrials.gov ID: NCT04644289
What this study is testing
What is olaparib?
olaparib is an investigational medicine, given as an once-daily pill taken by mouth, being studied as a potential treatment for epithelial ovarian cancer.
Also referred to as Lynparza.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This is a multi-center, prospective, open-label, phase II trial. Patients with suspected advanced ovarian cancer planned to undergo diagnostic laparoscopy for histologic confirmation and evaluation of disease spread will be registered into the trial after providing a 1st written informed consent.
- Phase 2: a mid-size study of how well it works
- Time commitment: about 24 months
- You might receive a placebo (an inactive treatment) instead of the study drug, decided by chance.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older, women only
You may be able to join if
- WoO pre-treatment (screening phase):
- Patients with presumed and previously untreated advanced stage ovarian cancer planned to undergo laparoscopy for histologic diagnosis and treatment...
- Patients willing and able to comply with the study protocol for the duration of the study including undergoing treatment and scheduled visits and...
- Patients able and willing to provide fresh frozen biopsy samples from laparoscopy as well as primary debulking for translational endpoints as well as...
- Patients able and willing to provide formaldehyde-fixed paraffin embedded (FFPE) tissue samples from laparoscopy and primary debulking surgery
You likely can't join if
- Medical conditions:
- Disease requiring urgent surgical intervention
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the study protocol
- Significant uncontrolled symptom burden (e.g. but not necessarily limited to large volume ascites, shortness of breath on exertion, pain requiring...
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, recent (within 3...
- Other malignancy unless curatively treated with no evidence of disease for ≥5 years except: adequately treated non-melanoma skin cancer, curatively...
See the full eligibility criteria
Who can join
- WoO pre-treatment (screening phase):
- Patients with presumed and previously untreated advanced stage ovarian cancer planned to undergo laparoscopy for histologic diagnosis and treatment planning
- Patients willing and able to comply with the study protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
- Patients able and willing to provide fresh frozen biopsy samples from laparoscopy as well as primary debulking for translational endpoints as well as serial liquid biopsies
- Patients able and willing to provide formaldehyde-fixed paraffin embedded (FFPE) tissue samples from laparoscopy and primary debulking surgery
- Patients aged ≥18 years
- Patients must be 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
- Provision of signed and dated, written ICF for the mandatory biomarker and genetic re-search as well as the clinical/therapeutic part of the study prior to any mandatory study specific procedures, sampling, and analyses
- Eastern cooperative oncology group (ECOG) performance status 0-1 (see Appendix 1)
- Patients must have a life expectancy ≥16 weeks
- Ability to take oral medication
- Postmenopausal or evidence of non-childbearing status for women of childbearing potential (WOCBP): negative serum pregnancy test within 28 days of study treatment and confirmed neagtive urine or serum pregnancy test...
- Amenorrheic 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 \>1 year interval since last menses
- surgical sterilisation (bilateral oophorectomy or hysterectomy)
- Women of childbearing potential (WOCBP) and their partners, who are sexually active, must agree to the use of 2 highly effective forms of contraception in combination. This should be started from the signing of the...
- Confirmed advanced (FIGO IIB/III/IV) high-grade, non-mucinous, non-clear cell epithelial ovarian, fallopian tube or primary peritoneal cancer or known (BReast CAncer) BRCA mutation and any histologic type
- Planned primary debulking surgery after confirmation of diagnosis and disease evaluation during laparoscopy
- Body weight \>30kg
- Patients 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 with no blood transfusion in the past 28 days
- Absolute neutrophil count (ANC) ≥1.5×10\^9/L
- Platelet count ≥100×10\^9/L
- Total bilirubin ≤1.5 × institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST), serum glutamic oxaloacetic transaminase (SGOT) / alanine aminotransferase (ALT), serum glutamic pyruvate transaminase (SGPT) ≤2.5 × institutional upper limit of normal unless liver...
- Patients must have creatinine clearance estimated of ≥51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test: Estimated creatinine clearance=((140-age [years])\ weight (kg))/(serum creatinine...
What rules you out
- Medical conditions:
- Disease requiring urgent surgical intervention
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the study protocol
- Significant uncontrolled symptom burden (e.g. but not necessarily limited to large volume ascites, shortness of breath on exertion, pain requiring opioid medication, signs of (sub)ileus
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, recent (within 3 months) myocardial infarction, uncontrolled hypertension, unstable...
- 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)...
- Resting electrocardiography (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, conges-tive heart...
- 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 a. Patients with irreversible toxicity...
- Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML).
- 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
- 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 before and during the study as long as...
- Evidence of central nervous system (CNS) or leptomeningeal metastases.
- 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...
- Patients unable to swallow orally administered medication and patients with gastrointestinal disorders or any status that might interfere with resorption of the respective study drugs, e.g. parenteral nutrition, short...
- Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
- History of active primary immunodeficiency
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B or hepatitis C.
- Active HBV is defined by a known positive HBsAg result. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible.
- Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA
- ECOG performance status (PS) ≥2 or general condition that might interfere with the compliance with the study protocol
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. Prior / concomitant therapy:
- Prior antineoplastic therapy for ovarian, fallopian tube or primary peritoneal cancer
- Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
- Any concurrent chemotherapy, investigational medicinal product (IMP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement...
- Patients planned for neoadjuvant chemotherapy or deemed unresectable at laparoscopy
- Concomitant use of known strong cytochrome P450 3A (CYP3A) inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir...
- Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz...
- Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
- History of allogenic organ transplantation
- Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
- Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
- Prior treatment with olaparib or any other poly [ADP-ribose] polymerase (PARP) inhibitor
- Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable, for timing refer to inclusion criteria no. 16) Other exclusions:
- Patients who are pregnant or breast-feeding or patients of reproductive potential who are not willing to employ effective birth control from screening to 6 months after the last dose of study drug(s).
- Involvement in the planning and/or conduct of the study
- Participation in another treatment clinical study with an investigational product during the last with the last 3 months.
- Concurrent enrolment in another clinical study, unless it is an observational (non-treatment) clinical study or during the follow-up period of an treatment study.
- Previous enrolment in the present study.
- Judgement by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements. Additional Durvalumab-specific...
- Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤28 days prior to the first dose of study...
- 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 coordinating investigator.
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the coordinating investigator.
- 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.
- Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of IP. Note: local surgery of isolated lesions for palliative intent is acceptable.
- History of allogenic organ transplantation.
- 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...
- 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
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial...
- History of another primary malignancy except for
- Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IMP and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
- History of leptomeningeal carcinomatosis
- 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.
- 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)
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known...
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IMP. Note: patients, if enrolled, should not receive live vaccine whilst receiving IMP and up to 30 days after the last dose of IMP.
- Prior randomisation or treatment in a previous durvalumab clinical study regardless of treatment arm assignment or other immunotherapies
- Patients who have received prior anti-programmed cell death-protein 1(PD-1), anti PD-L1 or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4):
- Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
- All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
- Must not have experienced a ≥grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. Note: Patients with endocrine AE of ≤grade 2 are permitted to enroll...
- Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if rechallenged, and not currently require maintenance...
- Patients planned for neoadjuvant chemotherapy (e.g. but not exclusively due to extend of disease spread or poor general condition etc.).
- (sub)ileus or signs of malignant bowel obstruction.
The study team makes the final eligibility decision.
Where it's taking place
- Mannheim, Baden-Wurttemberg, Germany
- München, Bavaria, Germany
- Hamburg, Free and Hanseatic City of Hamburg, Germany
- Essen, North Rine-Westphalia, Germany
- Dresden, Saxony, Germany
- Berlin, State of Berlin, Germany
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The study runs about 24 months per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling female, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Mannheim, Baden-Wurttemberg, Germany; München, Bavaria, Germany; Hamburg, Free and Hanseatic City of Hamburg, Germany; Essen, North Rine-Westphalia, Germany; Dresden, Saxony, Germany; Berlin, State of Berlin, Germany. Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.