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

NCT03378297 | Completed Early Phase 1

• 1 other identifier: 2017/1168
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief 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. 1.Metformin tablets, 850 mg x 2 orally.
2. 2.Acetylsalicylic acid tablets, 160 mg x1 orally
3. 3.Olaparib capsules, 300 mg x 2 orally
4. 4.Letrozol tablets, 2.5 mg x 1 orally

Conditions

Ovarian Cancer

Keywords

Ovarian cancer; Phase 0; Window-of-opportunity; Suregry; Repurposing; Metformin; Acetylsalicylic acid; Olaparib; Letrozol

Outcome Measures

Primary Outcomes (1)

• Changes in the expression of biomarkers

  A characterization of the tumor tissues from each patient will be performed (in pair). For each drug a specific biomarker is selected. The changes in expression of the defined biomarkers represent the primary outcome parameters. biomarkers related to the study agents and operability

  3 months

Study Arms (5)

Feasibility study cohort

NO INTERVENTION

Metformin

EXPERIMENTAL

850 mg

Drug: Metformin

Acetylsalicylic acid

EXPERIMENTAL

160 mg

Drug: Acetylsalicylic acid

Olaparib

EXPERIMENTAL

300 mg x 2

Drug: Olaparib

Letrozol

EXPERIMENTAL

2.5 mg

Drug: Letrozole

Interventions

Metformin DRUG

Metformin tablets 850 mg x 2 orally

Metformin

Acetylsalicylic acid DRUG

Acetylsalicylic acid tablets 160 mg x1 orally

Acetylsalicylic acid

Olaparib DRUG

Olaparib capsules 300 mg x 2 orally

Olaparib

Letrozole DRUG

Letrozol tablets 2.5 mg x 1 orally

Letrozol

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age 18 years or above
• 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.
• 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
• All laboratory tests for screening are taken maximum 14 days before start of treatment with study drug.
• Ability to understand a written informed consent document, and the willingness to sign it.

You may not qualify if:

• Inability to understand the information given and unable to consent and/or give the information requested, due to language, mental capacity, or disease.
• Inability to receive substances per os.
• 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.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to investigational drug or its composites.
• History of dysregulated coagulation or known bleeding disorder.
• 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.
• 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.
• 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.
• 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.
• Histologic diagnosis of non-High grade serous ovarian cancer.
• Presence of active tumors in the central nervous system and/or carcinomatous meningitis.
• Presence of active infection requiring systemic treatment.
• Current diagnosis of bowel obstruction (i.e. ileus or subileus).
• 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.

Sponsors & Collaborators

• Haukeland University Hospital: lead

Study Sites (2)

Helse Bergen HF, Haukeland University Hospital

Bergen, 5021, Norway

Location

Helse Stavanger HF, Stavanger University Hospital

Stavanger, 4068, Norway

Location

Related Publications (2)

• Torkildsen CF, Austdal M, Iversen AC, Bathen TF, Giskeodegard GF, Nilsen EB, Iversen GA, Sande RK, Bjorge L, Thomsen LCV. Primary Treatment Effects for High-Grade Serous Ovarian Carcinoma Evaluated by Changes in Serum Metabolites and Lipoproteins. Metabolites. 2023 Mar 12;13(3):417. doi: 10.3390/metabo13030417.

  PMID: 36984856 RESULT

• Torkildsen CF, Austdal M, Jarmund AH, Kleinmanns K, Lamark EK, Nilsen EB, Stefansson I, Sande RK, Iversen AC, Thomsen LCV, Bjorge L. New immune phenotypes for treatment response in high-grade serous ovarian carcinoma patients. Front Immunol. 2024 Jun 14;15:1394497. doi: 10.3389/fimmu.2024.1394497. eCollection 2024.

  PMID: 38947323 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Metformin; Aspirin; olaparib; Letrozole

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Line Bjørge, MD, PhD

  Helse-Bergen HF

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The first treatment cohort has a randomized design 2:1 (olaparib 32:control 16). The study is unblinded. In the following treatment arms are initiated each will included patients (n=32) will be offered the study-prespecified treatment drug.

Study Record Dates

• First Submitted: October 31, 2017
• First Posted: December 19, 2017
• Study Start: May 4, 2018
• Primary Completion: January 5, 2023
• Study Completion: January 5, 2023
• Last Updated: October 30, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

NO (2)