IMPACT: A Randomized WOO Study of Novel Therapeutic Agents in Women Triaged to Primary Surgery for EOC

• Status: Recruiting
• Trial end date: 2025-06-04
• Target enrollment: 0
• Participant gender: Female

Summary

The study will be conducted in women with advanced (stage IIIa-IV) ovarian cancer of the histologic subtype high grade serous carcinoma (HGSOC) who are going through a diagnostic laparoscopy. They will recieve treatment with a study agent for 10-14 days before surgery. They will be allocated to different study groups according to the diagnostic evaluation performed as standard of care at the department. The study is randomized and unblinded.

The primary investigational agents are:

1. Metformin tablets, 850 mg x 2 orally.

2. Acetylsalicylic acid tablets, 160 mg x1 orally

3. Olaparib capsules, 300 mg x 2 orally

4. Letrozol tablets, 2.5 mg x 1 orally

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Haukeland University Hospital
• Treatments: Aspirin; Letrozole; Metformin; Olaparib

Criteria

Inclusion Criteria:

1. Patients must have a clinical diagnosis of advanced ovarian, tubal or primary peritoneal cancer. Advanced disease is defined as at least stage 3 ovarian cancer. Definition of stages will be according to the Norwegian guidelines (Norsk Gynekologisk Forening, Veileder i gynekologisk onkologi, Kapittel: Eggstokk-, tube-, bukhinnekreft. Revisjon 01.12.15). If the clinical staff in charge of the patients plan to perform cytoreductive surgery, the patient can participate in the study, irrespective of ECOG performance status. Patients must not have metastases to the central nervous system and/or carcinomatous meningitis.

2. Age 18 years or above

3. Primary treatment setting. No prior treatment for gynecological cancer. Women who have been treated surgically for cervical cancer or precancerous lesions on the cervix can be included if she has finished treatment a year or more before current diagnosis of ovarian cancer.

4. Must have laboratory values as the following :

• White Blood Cells ≥ 1.5 x 109/L

• Platelets ≥ 100 x 109/L

• Hemoglobin ≥ 9g/dL (≥ 5.6 mmol/L)

• Creatinine ≤ 140 μmol/L; if creatinine is borderline, the creatinine clearance ≥ 40 mL/min;

• Bilirubin < 20 % above the upper limit of normal

• ASAT and ALAT ≤ 2.5 the upper limit of normal

• Albumin ≥ 2.5 g/L

• HbA1c < 8.0 %

• INR < 2.0

5. All laboratory tests for screening are taken maximum 14 days before start of treatment with study drug.

6. Ability to understand a written informed consent document, and the willingness to sign it.

7. Presence of adequate venous accesses for required study blood samples

Exclusion Criteria:

1. Inability to understand the information given and unable to consent and/or give the information requested, due to language, mental capacity, or disease.

2. Inability to receive substances per os.

3. Pregnancy. Pregnant women are excluded from this study, as terapeutic treatment for ovarian cancer includes teratogenic chemotherapy and surgical removal of the uterus and the ovaries.

4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to investigational drug or its composites.

5. History of dysregulated coagulation or known bleeding disorder.

6. Patients known to be Hepatitis B surface antigen positive, who have human immune deficiency virus (HIV) infection, and patients known or suspected to have active Hepatitis C infection.

7. Patients diagnosed or treated for other malignancy within 1 year of administration of the first dose of the study agent, or previously diagnosed with other malignancy and have residual disease. Patients with non-melanoma skin cancer or any type of carcinoma in situ will not be excluded if they have had a complete tumor resection.

8. Currently participate or have participated within the last four weeks of the first dose of the study agent in other studies including medication of participants.

9. Diagnosis of immune deficiency disorder or having received immunosuppressant treatment within the last 7 days before planned intake of the first dose of the study agent. Corticosteroids in physiologic doses can be acceptable.

10. Histologic diagnosis of non-High grade serous ovarian cancer.

11. Presence of active tumors in the central nervous system and/or carcinomatous meningitis.

12. Presence of active infection requiring systemic treatment.

13. Current diagnosis of bowel obstruction (i.e. ileus or subileus).

14. Individuals with indication of a condition, treatment or aberrant laboratory results that either can effect the results of this study or the sustainance of participation, such as renal failure stage ≥ 4, heart failure ≥ New York Heart Association (NYHA) grade III, a medical history of severe psychiatric disease, or a current diagnosis of alkoholism or drug addiction.