search
Back to results

Pembrolizumab With Chemotherapy in Front Line Advanced Ovarian, Primary Peritoneal and Fallopian Tube Cancer (MITO28MaNGOov4)

Primary Purpose

Ovarian Cancer

Status
Recruiting
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Pembrolizumab
Paclitaxel
Carboplatin
Sponsored by
National Cancer Institute, Naples
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring PD-L1 Expression, prognostic factors, predictive factors, Patient reported outcomes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

In order to be eligible for participation in this trial, the subject must:

  • Have a histologically confirmed diagnosis of advanced (FIGO stage IIIB, IIIC, IV) epithelial ovarian, primary peritoneal or fallopian tube cancer.
  • Have evidence of residual tumor after debulking surgery OR be non-eligible neither for primary surgery nor for neoadjuvant chemotherapy followed by interval debulking surgery
  • Be willing and able to provide written informed consent/assent for the trial.
  • Be at least 18 years of age on day of signing informed consent.
  • Have measurable disease based on RECIST 1.1.
  • Have tumor samples available for biomarker analysis.
  • Have a performance status of 0 or 1 on the ECOG Performance Scale.
  • 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. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Must be not eligible to receive Bevacizumab in combination with carboplatin and paclitaxel, due to contraindication, patient refusal or investigator choice
  • Demonstrate adequate organ function

Exclusion Criteria:

The subject must be excluded from participating in the trial if the subject:

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent or investigational device and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • 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 (Grade 0 or 1 at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (Grade 0 or 1 at baseline) from adverse events due to a previously administered agent.

Note: Subjects with Grade 1 or 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.
  • 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 28 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 a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • 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 or other co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137) or drug specifically targeting T-cell co-stimulation or checkpoint pathways
  • 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.

Sites / Locations

  • Ospedale Generale Regionale "F. Miulli "Recruiting
  • Istituto Tumori Giovanni Paolo IIRecruiting
  • Spedali Civili - Università di BresciaRecruiting
  • Ospedale Senatore Antonio PerrinoRecruiting
  • Fondazione del Piemonte per l'OncologiaRecruiting
  • Istituto Romagnolo per lo Studio e la Cura dei TumoriRecruiting
  • Istituto Nazionale TumoriRecruiting
  • AOU Policlinico Federico IIRecruiting
  • AOU Università degli studi della Campania "Luigi Vanvitelli"Recruiting
  • Istituto Nazionale dei TumoriRecruiting
  • Ospedale SilvestriniRecruiting
  • Ospedale S. Giovanni Calibita FatebenefratelliRecruiting
  • Policlinico Universitario Gemelli Università Cattolica del Sacro Cuore

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

First-line chemotherapy with pembrolizumab

Arm Description

Pembrolizumab 200 mg i.v. on Day 1 every 3 weeks for up to 22 cycles Paclitaxel 175 mg/m2 on Day 1 every 3 weeks for up to 6 cycles Carboplatin (AUC 5) on Day 1 every 3 weeks for up to 6 cycles

Outcomes

Primary Outcome Measures

Proportion of patients free from progression

Secondary Outcome Measures

progression free survival
overall survival
number of patients with complete and partial responses
worst grade toxicity per patient
according to Common Toxicity Criteria for Adverse Events v. 4.03
changes in patient-reported outcome (PRO) scores of disease-related symptoms from baseline

Full Information

First Posted
January 19, 2018
Last Updated
March 23, 2023
Sponsor
National Cancer Institute, Naples
Collaborators
Mario Negri Institute for Pharmacological Research
search

1. Study Identification

Unique Protocol Identification Number
NCT03410784
Brief Title
Pembrolizumab With Chemotherapy in Front Line Advanced Ovarian, Primary Peritoneal and Fallopian Tube Cancer
Acronym
MITO28MaNGOov4
Official Title
A Phase II Clinical Trial of Pembrolizumab in Combination With Carboplatin-paclitaxel in Patients With Advanced (Stage III B-C-IV) Ovarian, Primary Peritoneal and Fallopian Tube Cancer: MITO28/MANGO OV4 Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2018 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute, Naples
Collaborators
Mario Negri Institute for Pharmacological Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is designed to assess the therapeutic efficacy and toxicity of the combination chemotherapy Paclitaxel and Carboplatin with Pembrolizumab in patients with advanced ovarian cancer. The main objective is to test whether the therapeutic intervention benefits the patient evaluating the number of subjects who are progression-free after 18 months from the beginning of the first line treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
PD-L1 Expression, prognostic factors, predictive factors, Patient reported outcomes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
First-line chemotherapy with pembrolizumab
Arm Type
Other
Arm Description
Pembrolizumab 200 mg i.v. on Day 1 every 3 weeks for up to 22 cycles Paclitaxel 175 mg/m2 on Day 1 every 3 weeks for up to 6 cycles Carboplatin (AUC 5) on Day 1 every 3 weeks for up to 6 cycles
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
Pembrolizumab 200 mg i.v. on Day 1 every 3 weeks up to 22 cycles
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
Paclitaxel 175 mg/m2 i.v. on Day 1 every 3 weeks up to 6 cycles
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Carboplatin (AUC 5) i.v. on Day 1 every 3 weeks for up to 6 cycles
Primary Outcome Measure Information:
Title
Proportion of patients free from progression
Time Frame
18 months from beginning of first line treatment
Secondary Outcome Measure Information:
Title
progression free survival
Time Frame
3 years
Title
overall survival
Time Frame
5 years
Title
number of patients with complete and partial responses
Time Frame
18 months
Title
worst grade toxicity per patient
Description
according to Common Toxicity Criteria for Adverse Events v. 4.03
Time Frame
evaluated every 3 weeks up to 18 months
Title
changes in patient-reported outcome (PRO) scores of disease-related symptoms from baseline
Time Frame
up to 18 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: In order to be eligible for participation in this trial, the subject must: Have a histologically confirmed diagnosis of advanced (FIGO stage IIIB, IIIC, IV) epithelial ovarian, primary peritoneal or fallopian tube cancer. Have evidence of residual tumor after debulking surgery OR be non-eligible neither for primary surgery nor for neoadjuvant chemotherapy followed by interval debulking surgery Be willing and able to provide written informed consent/assent for the trial. Be at least 18 years of age on day of signing informed consent. Have measurable disease based on RECIST 1.1. Have tumor samples available for biomarker analysis. Have a performance status of 0 or 1 on the ECOG Performance Scale. 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. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Must be not eligible to receive Bevacizumab in combination with carboplatin and paclitaxel, due to contraindication, patient refusal or investigator choice Demonstrate adequate organ function Exclusion Criteria: The subject must be excluded from participating in the trial if the subject: Is currently participating and receiving study therapy or has participated in a study of an investigational agent or investigational device and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. 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 (Grade 0 or 1 at baseline) from adverse events due to agents administered more than 4 weeks earlier. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (Grade 0 or 1 at baseline) from adverse events due to a previously administered agent. Note: Subjects with Grade 1 or 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. 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 28 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 a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. 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 or other co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137) or drug specifically targeting T-cell co-stimulation or checkpoint pathways 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Francesco Perrone, M.D., Ph.D.
Phone
+39 081 5903571
Email
f.perrone@istitutotumori.na.it
First Name & Middle Initial & Last Name or Official Title & Degree
Gennaro Daniele, M.D., Ph.D.
Phone
+39 081 5903383
Email
g.daniele@istitutotumori.na.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sandro Pignata, M.D., Ph.D.
Organizational Affiliation
National Cancer Institute, Naples
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nicoletta Colombo, M.D.
Organizational Affiliation
European Institute of Oncology
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Francesco Perrone, M.D., Ph.D.
Organizational Affiliation
National Cancer Institute, Naples
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gennaro Daniele, M.D., Ph.D.
Organizational Affiliation
National Cancer Institute, Naples
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ciro Gallo, M.D.
Organizational Affiliation
University of Campania "Luigi Vanvitelli"
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ospedale Generale Regionale "F. Miulli "
City
Acquaviva delle Fonti
Country
Italy
Individual Site Status
Recruiting
Facility Name
Istituto Tumori Giovanni Paolo II
City
Bari
Country
Italy
Individual Site Status
Recruiting
Facility Name
Spedali Civili - Università di Brescia
City
Brescia
Country
Italy
Individual Site Status
Recruiting
Facility Name
Ospedale Senatore Antonio Perrino
City
Brindisi
Country
Italy
Individual Site Status
Recruiting
Facility Name
Fondazione del Piemonte per l'Oncologia
City
Candiolo
Country
Italy
Individual Site Status
Recruiting
Facility Name
Istituto Romagnolo per lo Studio e la Cura dei Tumori
City
Meldola
Country
Italy
Individual Site Status
Recruiting
Facility Name
Istituto Nazionale Tumori
City
MIlano
Country
Italy
Individual Site Status
Recruiting
Facility Name
AOU Policlinico Federico II
City
Napoli
Country
Italy
Individual Site Status
Recruiting
Facility Name
AOU Università degli studi della Campania "Luigi Vanvitelli"
City
Napoli
Country
Italy
Individual Site Status
Recruiting
Facility Name
Istituto Nazionale dei Tumori
City
Napoli
Country
Italy
Individual Site Status
Recruiting
Facility Name
Ospedale Silvestrini
City
Perugia
Country
Italy
Individual Site Status
Recruiting
Facility Name
Ospedale S. Giovanni Calibita Fatebenefratelli
City
Roma
Country
Italy
Individual Site Status
Recruiting
Facility Name
Policlinico Universitario Gemelli Università Cattolica del Sacro Cuore
City
Roma
Country
Italy
Individual Site Status
Not yet recruiting

12. IPD Sharing Statement

Learn more about this trial

Pembrolizumab With Chemotherapy in Front Line Advanced Ovarian, Primary Peritoneal and Fallopian Tube Cancer

We'll reach out to this number within 24 hrs