Ovarian CancerEarly Phase 1IMPACTNCT03378297
IMPACT: A Randomized WOO Study of Novel Therapeutic Agents in Women Triaged to Primary Surgery for EOC
A Early Phase 1 study testing Metformin, Acetylsalicylic acid and Olaparib in people with Ovarian Cancer, run by Haukeland University Hospital at 2 sites in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- Metformin, Acetylsalicylic acid and Olaparib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 2 sitesNorway
- Study dates
- 4 May 2018to 5 Jan 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 16Show fewer
- 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.
- Presence of adequate venous accesses for required study blood samples
Who cannot join
- 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.
Show all 14Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
Norway2 sites
Helse Bergen HF, Haukeland University Hospital
Bergen, 5021
Helse Stavanger HF, Stavanger University Hospital
Stavanger, 4068
About this study
Official title: IMPACT: A Phase 0 Randomized Window-of-Opportunity Study of Novel and Repurposed Therapeutic Agents in Women Triaged to Primary Surgery for Advanced Epithelial Ovarian Cancer in Stages IIIa - IV.
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:
- Metformin tablets, 850 mg x 2 orally.
- Acetylsalicylic acid tablets, 160 mg x1 orally
- Olaparib capsules, 300 mg x 2 orally
- Letrozol tablets, 2.5 mg x 1 orally
Read the detailed description
The women who agree to participate in the study prior to the laparoscopic evaluation, will be allocated to different study groups according to the diagnostic evaluation performed as standard of care at the department. During inclusion in the first study cohort, the olaparib cohort (n=32), an additional 16 women are randomized as controls and will not receive neither any study drug nor placebo. The study is unblinded. There will not be randomized controls into the other study cohorts, as the control group collected will be utilized as controls for all study agents.
The women in Arm I will be included in the WOO trial, and will be treated with the study agent for 10-14 days prior to tumor reductive surgery, starting the day of laparoscopic surgery (+1 day). The treatment will be discontinued at the time of tumor reductive surgery.
Currently fourmore agents are evaluated as of particular interest, as well as feasible to introduce, in the WOO study set up: metformin, acetylsalicylic acid, olaparib, and letrozol. The first agent listed in the protocol, metformin, will be given to 32 consequtive women, and drug related analyses will thereafter be performed. The next 32 women included in the study will receive the next agent on the list, acetylsalicylic acid, while analyses for the metformin group is ongoing, and after the acetylsalicylic acid study group has been included the next agent on the list is introduced. Should any of the included women be non-eligable to receive one study drug, they will either receive the next agent on the list of the four study drugs, if eligable, or be included as control.
The women in Arm II who agree to participate in the study will not receive the study medication, but standard neoadjuvant chemotherapy until having decreased tumor load radiologically estimated and scheduled for optimal debulking procedure according to standard treatment of this group of patients. Samples from these women will be used as control in the translational part of the where we aim to identify potential molecular pathway(s) and cell type(s) that may be responsible for suboptimal debulking.
During the cancer-directed surgical procedure in participants in both Arms additional tissue samples from matching sites, preferably from tissues removed as part of the operation, as well as blood and urine samples, are obtained for comparative analysis. By use of the collected samples we can evaluate the clinical and molecular impact of the study agents among those triaged to primary cytoreductive surgery. Promising therapeutic targets identified might later be explored separately in one of the consequtive treatment study groups.
After the debulking surgery all women will follow the recommended standard of care, including chemotherapy and consolidating bevacisumab where indicated.
- Conditions
- Ovarian Cancer
- Keywords
- Ovarian cancer, Phase 0, Window-of-opportunity, Suregry, Repurposing, Metformin, Acetylsalicylic acid, Olaparib, Letrozol
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Metformin tablets 850 mg x 2 orally
Acetylsalicylic acidDrug
Acetylsalicylic acid tablets 160 mg x1 orally
OlaparibDrug
Olaparib capsules 300 mg x 2 orally
LetrozoleDrug
Letrozol tablets 2.5 mg x 1 orally
| Study group | Role | What they receive |
|---|---|---|
| Feasibility study cohort | No intervention | Not described |
| Metformin | Experimental | 850 mg Receives: Drug: Metformin |
| Acetylsalicylic acid | Experimental | 160 mg Receives: Drug: Acetylsalicylic acid |
| Olaparib | Experimental | 300 mg x 2 Receives: Drug: Olaparib |
| Letrozol | Experimental | 2.5 mg Receives: Drug: Letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2017
- Study start4 May 2018
- Primary completion5 Jan 2023
- Study completion5 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by Haukeland University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Line Bjørge, MD, PhD, Principal investigator, Helse-Bergen HF
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03378297
- Sponsor's protocol ID
- 2017/1168
- Acronym
- IMPACT
- Status last verified
- May 2024
- First submitted
- 31 Oct 2017
- Last updated
- 30 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36984856Torkildsen 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.
PubMed 38947323
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IMPACT: A Phase 0 Randomized Window-of-Opportunity Study of Novel and Repurposed Therapeutic Agents in Women Triaged to Primary Surgery for Advanced Epithelial Ovarian Cancer in Stages IIIa - IV.
- ClinicalTrials.gov ID
- NCT03378297
- Acronym / sponsor ID
- IMPACT / 2017/1168
- Conditions
- Ovarian Cancer
- Keywords
- Ovarian cancer, Phase 0, Window-of-opportunity, Suregry, Repurposing, Metformin, Acetylsalicylic acid, Olaparib
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Haukeland University HospitalUniversity, hospital or other
- Study start
- 4 May 2018 (actual)
- Primary completion
- 5 Jan 2023 (actual)
- Study completion
- 5 Jan 2023 (actual)
- First posted
- 19 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Metformin tablets, 850 mg x 2 orally.
- Acetylsalicylic acid tablets, 160 mg x1 orally
- Olaparib capsules, 300 mg x 2 orally
- Letrozol tablets, 2.5 mg x 1 orally
Detailed description
The women who agree to participate in the study prior to the laparoscopic evaluation, will be allocated to different study groups according to the diagnostic evaluation performed as standard of care at the department. During inclusion in the first study cohort, the olaparib cohort (n=32), an additional 16 women are randomized as controls and will not receive neither any study drug nor placebo. The study is unblinded. There will not be randomized controls into the other study cohorts, as the control group collected will be utilized as controls for all study agents.
The women in Arm I will be included in the WOO trial, and will be treated with the study agent for 10-14 days prior to tumor reductive surgery, starting the day of laparoscopic surgery (+1 day). The treatment will be discontinued at the time of tumor reductive surgery.
Currently fourmore agents are evaluated as of particular interest, as well as feasible to introduce, in the WOO study set up: metformin, acetylsalicylic acid, olaparib, and letrozol. The first agent listed in the protocol, metformin, will be given to 32 consequtive women, and drug related analyses will thereafter be performed. The next 32 women included in the study will receive the next agent on the list, acetylsalicylic acid, while analyses for the metformin group is ongoing, and after the acetylsalicylic acid study group has been included the next agent on the list is introduced. Should any of the included women be non-eligable to receive one study drug, they will either receive the next agent on the list of the four study drugs, if eligable, or be included as control.
The women in Arm II who agree to participate in the study will not receive the study medication, but standard neoadjuvant chemotherapy until having decreased tumor load radiologically estimated and scheduled for optimal debulking procedure according to standard treatment of this group of patients. Samples from these women will be used as control in the translational part of the where we aim to identify potential molecular pathway(s) and cell type(s) that may be responsible for suboptimal debulking.
During the cancer-directed surgical procedure in participants in both Arms additional tissue samples from matching sites, preferably from tissues removed as part of the operation, as well as blood and urine samples, are obtained for comparative analysis. By use of the collected samples we can evaluate the clinical and molecular impact of the study agents among those triaged to primary cytoreductive surgery. Promising therapeutic targets identified might later be explored separately in one of the consequtive treatment study groups.
After the debulking surgery all women will follow the recommended standard of care, including chemotherapy and consolidating bevacisumab where indicated.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Feasibility study cohort | No intervention | – |
| Metformin | Experimental | Drug: Metformin850 mg |
| Acetylsalicylic acid | Experimental | Drug: Acetylsalicylic acid160 mg |
| Olaparib | Experimental | Drug: Olaparib300 mg x 2 |
| Letrozol | Experimental | Drug: Letrozole2.5 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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 :
- All laboratory tests for screening are taken maximum 14 days before start of treatment with study drug.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminMetformin tablets 850 mg x 2 orally | Drug | Metformin |
| Acetylsalicylic acidAcetylsalicylic acid tablets 160 mg x1 orally | Drug | Acetylsalicylic acid |
| OlaparibOlaparib capsules 300 mg x 2 orally | Drug | Olaparib |
| LetrozoleLetrozol tablets 2.5 mg x 1 orally | Drug | Letrozol |
Primary outcome
Changes in the expression of biomarkers
Time frame: 3 months
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2024.
- Results publication: PubMed 36984856Torkildsen 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.
- Derived from this study: PubMed 38947323Torkildsen 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Line Bjørge, MD, PhD principal investigator
Helse-Bergen HF
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Metformin, Acetylsalicylic acid and Olaparib in people with Ovarian Cancer, run by Haukeland University Hospital at 2 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the expression of biomarkers (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03378297, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2024.