Study on MK-3475 Plus Chemotherapy Versus Chemotherapy Alone in Recurrent, Platinum-resistant Ovarian Cancer

NCT03539328 | Unknown Phase 2 DMC

• 1 other identifier: 180-17
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 1

Brief 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 chemotherapy alone.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  The combination of pembrolizumab and chemotherapy is expected to increase overall survival with respect to chemotherapy alone

  from randomization to the date of death, assessed up to 44 months

Secondary Outcomes (7)

• Progression free survival (PFS)

  from randomization to the date of radiological/clinical progression of disease or death, assessed up to 44 months

• Response rate

  44 months

• Adverse events

  44 months

• Exploratory Objective: relationship between PD-L1 expression and response to Pembrolizumab treatment.

  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

  At screening phase (within 28 days before the start of treatment) and every 3 cycles (each cycle is 28 days), up to 44 months

Study Arms (2)

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

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

Drug: Pembrolizumab; Drug: Gemcitabine; Drug: Paclitaxel; Drug: Liposomal Doxorubicin

Interventions

Pembrolizumab DRUG

Humanized antibody used in cancer immunotherapy.

Pembrolizumab

Gemcitabine DRUG

Chemotherapy medication

Pembrolizumab; Standard treatment

Paclitaxel DRUG

Chemotherapy medication

Pembrolizumab; Standard treatment

Liposomal Doxorubicin DRUG

Chemotherapy medication

Pembrolizumab; Standard treatment

Eligibility Criteria

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

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

National Cancer Institute

Milan, 20133, Italy

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

pembrolizumab; Gemcitabine; Paclitaxel; liposomal doxorubicin

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)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Domenica Lorusso, MD

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Domenica Lorusso, MD

CONTACT

0223903697; domenica.lorusso@istitutotumori.mi.it

Serena Giolitto, MSc

CONTACT

0223903882; serena.giolitto@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2018
• First Posted: May 29, 2018
• Study Start: June 1, 2018
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2022
• Last Updated: May 29, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)