Ovarian CancerPhase 2MITO27NCT03539328
Study on MK-3475 Plus Chemotherapy Versus Chemotherapy Alone in Recurrent, Platinum-resistant Ovarian Cancer
A Phase 2 study testing Pembrolizumab, Gemcitabine and Paclitaxel in people with Ovarian Cancer, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
Trial summary
The study is designed to assess the therapeutic efficacy and toxicity of the combination chemotherapy with pembrolizumab in recurrent, platinum resistant OC patients. The main objective is to test whether the therapeutic intervention benefits the patients evaluating the increase in overall survival with respect to… 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?
- Pembrolizumab, Gemcitabine and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 138 participants
- Where
- 1 siteItaly
- Study dates
- Jun 2018to Apr 2022
- Phase
- Phase 2
- 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
- Platinum resistant (platinum free interval 1-6 months from last platinum dose) ovarian, Fallopian tube or primary peritoneal cancer;
- Be willing and able to provide written informed consent/assent for the trial;
- Be 18 years of age on day of signing informed consent;
- Have measurable disease or evaluable based on RECIST 1.1 (patients with only CA 125 increase without evidence of disease are not included);
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen;
- Have a performance status of 0 or 1 on the ECOG Performance Scale;
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- Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation;
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 6.5.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment;
- Has received >2 previous CHT lines;
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment;
- Has a known history of active TB (Bacillus Tuberculosis);
- Hypersensitivity to pembrolizumab or any of its excipients;
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier;
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- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent:
- Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study;
- Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy;
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer and other solid tumors within the last 2 years;
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability;
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment;
- Has an history of, or any actual evidence of active, non-infectious pneumonitis that required steroids treatment;
- Has an active infection requiring systemic therapy;
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator;
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial;
- Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment;
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent;
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies);
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected);
- Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: MITO27: Randomized Phase II Study on MK-3475 Plus Chemotherapy Versus Chemotherapy Alone in Recurrent, Platinum-resistant Ovarian Cancer
The study is designed to assess the therapeutic efficacy and toxicity of the combination chemotherapy with pembrolizumab in recurrent, platinum resistant OC patients. The main objective is to test whether the therapeutic intervention benefits the patients evaluating the increase in overall survival with respect to chemotherapy alone.
Read the detailed description
This is a multicenter, randomized, open-label trial, designed to assess the therapeutic efficacy and toxicity of the combination chemotherapy with pembrolizumab in recurrent, platinum resistant OC patients. The main objective is to test whether the therapeutic intervention benefits the patients evaluating the increase in overall survival with respect to chemotherapy alone.
Eligible patients will be randomized 1:1 to receive:
ARM A:
Pegylated Liposomal Doxorubicin 40 mg/mq iv q 28 Weekly Paclitaxel 80 mg/mq d 1,8,15 q 28 Gemcitabine 1000 mg/mq d 1,8 q 21 At physician' discretion or
ARM B:
Pegylated Liposomal Doxorubicin 40 mg/mq iv q 28 Weekly Paclitaxel 80 mg/mq d 1,8,15 q 28 Gemcitabine 1000 mg/mq d 1,8 q 21 plus Pembrolizumab 200 mg d1 q 21 iv infusion in 30 minutes In both arms patients will receive treatments until disease progression, unacceptable toxicity of patient's refusal. Patients will receive at least 6 to 8 cycles of chemotherapy at physician's discretion. In the experimental arm patients who stop chemotherapy for toxicity reasons and whose disease is at least in stabilization, may continue treatment with Pembrolizumab as single agent.
Patients will be stratified according to the number of previous chemotherapy lines (1 vs >1) and measurable/evaluable disease.
- Conditions
- Ovarian Cancer
- Being tested
- Pembrolizumab, Gemcitabine, Paclitaxel, Liposomal Doxorubicin
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Humanized antibody used in cancer immunotherapy.
GemcitabineDrug
Chemotherapy medication
PaclitaxelDrug
Chemotherapy medication
Liposomal DoxorubicinDrug
Chemotherapy medication
| Study group | Role | What they receive |
|---|---|---|
| Standard treatment | Other | Pegylated Liposomal Doxorubicin 40 mg/mq iv q 28 or Weekly Paclitaxel 80 mg/mq d 1,8,15 q 28 or Gemcitabine 1000 mg/mq d 1,8 q 21 or At physician' discretion Receives: Drug: Gemcitabine; Drug: Paclitaxel; Drug: Liposomal Doxorubicin |
| Pembrolizumab | Experimental | Pegylated Liposomal Doxorubicin 40 mg/mq iv q 28 or Weekly Paclitaxel 80 mg/mq d 1,8,15 q 28 or Gemcitabine 1000 mg/mq d 1,8 q 21 or At physician' discretion plus Pembrolizumab 200 mg d1 q 21 iv infusion in 30 minutes Receives: Drug: Pembrolizumab; Drug: Gemcitabine; Drug: Paclitaxel; Drug: Liposomal Doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
The combination of pembrolizumab and chemotherapy is expected to increase overall survival with respect to chemotherapy alone
Measured: from randomization to the date of death, assessed up to 44 months
Secondary outcomes (7)
Progression free survival (PFS)
The combination of pembrolizumab and chemotherapy is expected to increase progression free survival with respect to chemotherapy alone
Measured: from randomization to the date of radiological/clinical progression of disease or death, assessed up to 44 months
Response rate
The combination of pembrolizumab and chemotherapy is expected to increase response rate with respect to chemotherapy alone.
Measured: 44 months
Adverse events
Incidence of adverse events, according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0
Measured: 44 months
Exploratory Objective: relationship between PD-L1 expression and response to Pembrolizumab treatment.
PD-L1 expression in tumor tissue will be characterized by immunohistochemistry to explore the relationship between tumor PD-L1 expression and response to treatment with pembrolizumab.
Measured: At screening phase: within 28 days before the start of treatment
Exploratory Objective: association between anti-tumor activity from genetic alterations that may indicate a specific genotype reflective of greater dependency on PD-1/PD-L1 checkpoint function or other immune checkpoint signaling pathways
DNA isolated from blood or tumor tissue will be analyzed in order to identify genetic alterations and to evaluate specific genetic alterations that may correlate with clinical response to Pembrolizumab.
Measured: At screening phase (within 28 days before the start of treatment) and every 3 cycles (each cycle is 28 days), up to 44 months
Quality of life
To assess patient-reported outcome (PRO) of patients receiving chemotherapy plus pembrolizumab with respect to patients receiving chemotherapy alone utilizing the disease-related symptoms - physical subscale of the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy FACT-Ovarian Symptom Index 18 (FOSI-18) Changes. The time to an event in PRO (Patient Reported Outcome) of worsening of disease symptoms will be defined as the time from randomization to a 4-point reduction in the FACT-O questionnaire.
Measured: 44 months
Quality of life
To assess patient-reported outcome (PRO) of patients receiving chemotherapy plus pembrolizumab with respect to patients receiving chemotherapy alone using Euro- Quality of Life 5D tool, indicating which statements best describe the patient health state regarding: mobility, self-care, usual activities, pain/discomfort, anxiety/depression
Measured: 44 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2018
- Study startJun 2018 (estimated)
- Primary completionApr 2022 (estimated)
- Study completionApr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoThe 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 138 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Domenica Lorusso, MD, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03539328
- Sponsor's protocol ID
- 180-17
- Acronym
- MITO27
- Status last verified
- Feb 2018
- First submitted
- 23 Mar 2018
- Last updated
- 29 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MITO27: Randomized Phase II Study on MK-3475 Plus Chemotherapy Versus Chemotherapy Alone in Recurrent, Platinum-resistant Ovarian Cancer
- ClinicalTrials.gov ID
- NCT03539328
- Acronym / sponsor ID
- MITO27 / 180-17
- Conditions
- Ovarian Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 138 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Study start
- Jun 2018 (estimated)
- Primary completion
- Apr 2022 (estimated)
- Study completion
- Apr 2022 (estimated)
- First posted
- 29 May 2018 (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 is designed to assess the therapeutic efficacy and toxicity of the combination chemotherapy with pembrolizumab in recurrent, platinum resistant OC patients. The main objective is to test whether the therapeutic intervention benefits the patients evaluating the increase in overall survival with respect to chemotherapy alone.
Detailed description
This is a multicenter, randomized, open-label trial, designed to assess the therapeutic efficacy and toxicity of the combination chemotherapy with pembrolizumab in recurrent, platinum resistant OC patients. The main objective is to test whether the therapeutic intervention benefits the patients evaluating the increase in overall survival with respect to chemotherapy alone.
Eligible patients will be randomized 1:1 to receive:
ARM A:
Pegylated Liposomal Doxorubicin 40 mg/mq iv q 28 Weekly Paclitaxel 80 mg/mq d 1,8,15 q 28 Gemcitabine 1000 mg/mq d 1,8 q 21 At physician' discretion or
ARM B:
Pegylated Liposomal Doxorubicin 40 mg/mq iv q 28 Weekly Paclitaxel 80 mg/mq d 1,8,15 q 28 Gemcitabine 1000 mg/mq d 1,8 q 21 plus Pembrolizumab 200 mg d1 q 21 iv infusion in 30 minutes In both arms patients will receive treatments until disease progression, unacceptable toxicity of patient's refusal. Patients will receive at least 6 to 8 cycles of chemotherapy at physician's discretion. In the experimental arm patients who stop chemotherapy for toxicity reasons and whose disease is at least in stabilization, may continue treatment with Pembrolizumab as single agent.
Patients will be stratified according to the number of previous chemotherapy lines (1 vs >1) and measurable/evaluable disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard treatment | Other | Drug: Gemcitabine, Drug: Paclitaxel, Drug: Liposomal DoxorubicinPegylated Liposomal Doxorubicin 40 mg/mq iv q 28 or Weekly Paclitaxel 80 mg/mq d 1,8,15 q 28 or Gemcitabine 1000 mg/mq d 1,8 q 21 or At physician' discretion |
| Pembrolizumab | Experimental | Drug: Pembrolizumab, Drug: Gemcitabine, Drug: Paclitaxel, Drug: Liposomal DoxorubicinPegylated Liposomal Doxorubicin 40 mg/mq iv q 28 or Weekly Paclitaxel 80 mg/mq d 1,8,15 q 28 or Gemcitabine 1000 mg/mq d 1,8 q 21 or At physician' discretion plus Pembrolizumab 200 mg d1 q 21 iv infusion in 30 minutes |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Platinum resistant (platinum free interval 1-6 months from last platinum dose) ovarian, Fallopian tube or primary peritoneal cancer;
- Be willing and able to provide written informed consent/assent for the trial;
- Be 18 years of age on day of signing informed consent;
- Have measurable disease or evaluable based on RECIST 1.1 (patients with only CA 125 increase without evidence of disease are not included);
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen;
Key exclusion criteria (21 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment;
- Has received >2 previous CHT lines;
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment;
- Has a known history of active TB (Bacillus Tuberculosis);
- Hypersensitivity to pembrolizumab or any of its excipients;
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 |
|---|---|---|
| PembrolizumabHumanized antibody used in cancer immunotherapy. | Drug | Pembrolizumab |
| GemcitabineChemotherapy medication | Drug | Pembrolizumab, Standard treatment |
| PaclitaxelChemotherapy medication | Drug | Pembrolizumab, Standard treatment |
| Liposomal DoxorubicinChemotherapy medication | Drug | Pembrolizumab, Standard treatment |
Primary outcome
Overall survival (OS)
Time frame: from randomization to the date of death, assessed up to 44 months
The combination of pembrolizumab and chemotherapy is expected to increase overall survival with respect to chemotherapy alone
7 secondary outcomes
Progression free survival (PFS)
Time frame: from randomization to the date of radiological/clinical progression of disease or death, assessed up to 44 months
Response rate
Time frame: 44 months
Adverse events
Time frame: 44 months
Exploratory Objective: relationship between PD-L1 expression and response to Pembrolizumab treatment.
Time frame: At screening phase: within 28 days before the start of treatment
Exploratory Objective: association between anti-tumor activity from genetic alterations that may indicate a specific genotype reflective of greater dependency on PD-1/PD-L1 checkpoint function or other immune checkpoint signaling pathways
Time frame: At screening phase (within 28 days before the start of treatment) and every 3 cycles (each cycle is 28 days), up to 44 months
Quality of life
Time frame: 44 months
Quality of life
Time frame: 44 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2018.
- 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.
Domenica Lorusso, MD principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab, Gemcitabine and Paclitaxel in people with Ovarian Cancer, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
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 9 inclusion and 21 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: status not confirmed, as of the sponsor's last update on 29 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Domenica Lorusso, MD (0223903697, domenica.lorusso@istitutotumori.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (OS) (time frame: from randomization to the date of death, assessed up to 44 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 May 2018; AzTrials last refreshed its copy on 6 Nov 2026.