Phase II Trial of Pembrolizumab in Combination With Doxorubicin in Advanced, Recurrent or Metastatic Endometrial Cancer (TOPIC)

Vall d'Hebron Institute of Oncology7 sites in 1 country48 target enrollmentMay 30, 2018

ConditionsEndometrial Neoplasms

InterventionsPembrolizumab

DrugsPembrolizumab

Overview

Phase: Phase 2
Intervention: Pembrolizumab
Conditions: Endometrial Neoplasms
Sponsor: Vall d'Hebron Institute of Oncology
Enrollment: 48
Locations: 7
Primary Endpoint: PFS rate at 6 months according to RECIST 1.1 criteria
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a non-randomized, single arm, multi-center, phase II study of pembrolizumab in combination with doxorubicin in subjects with recurrent/metastatic endometrial cancer.

Registry

clinicaltrials.gov

Start Date

May 30, 2018

End Date

August 26, 2021

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

Vall d'Hebron Institute of Oncology

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Be willing and able to provide written informed consent/assent for the trial. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research
•Be \>18 years of age on day of signing informed consent.
•Have a histologically or cytologically-documented, advanced (metastatic and/or unresectable) endometrial carcinoma that is incurable and for which prior platinum-based chemotherapy for first-line treatment has failed. All epithelial endometrial histologies are eligible including: endometrioid, serous, clear-cell carcinoma, squamous or carcinosarcoma. Sarcomas and mesenchymal tumors are excluded.
•Eligible subjects must have had only 1 prior line of systemic platinum-based chemotherapy for advanced, recurrent or metastatic endometrial cancer. Patients who have had 2 or more prior chemotherapeutic regimens for advanced, recurrent, or metastatic endometrial cancer are not allowed.
•Note: Prior neoadjuvant or adjuvant chemotherapy included in initial treatment may not be considered first- or later-line treatment unless such treatments were completed less than 6 months prior to the current tumor recurrence. Prior treatment may include chemotherapy, chemotherapy/radiation therapy, and/or consolidation/maintenance therapy.
•Prior hormonal treatment is not considered a line of therapy in any setting. Prior targeted therapy no directed against PD-1, PD-L1, PD-L2 pathway or any other immunemodulating mAb (including ipilimumab and any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) are allowed.
•Have measurable disease based on RECIST 1.1, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm in long axis when measured by CT, MRI, or caliper measurement by clinical exam. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI. Tumor lesions situated in a previously irradiated area are considered measurable if progression according to RECIST 1.1 criteria has been demonstrated in such lesions. Patients must have radiographic evidence of disease progression following the most recent line of treatment. Areas of previous radiation may not serve as measurable disease unless there is evidence of progression post radiation according to RECIST 1.1 criteria. Patients with only one area of measureable disease that consent to have it biopsied are still eligible.
•Availability of fresh or archival FFPE tumor specimens for analysis for biomarker analysis from a tumor lesion not previously irradiated (exceptions may be considered after Sponsor consultation). (See Procedure Manual for detailed instructions). Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion if archival specimen is not available. Newly-obtained is defined as a specimen obtained up to 4 weeks (28 days) prior to initiation of treatment on Day
•Have a performance status of 0 or 1 on the ECOG Performance Scale.
•Demonstrate adequate organ function as defined in Table 2, all screening labs should be performed within 7 days of treatment initiation.

Exclusion Criteria

•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.
•Receipt of 2 or more prior chemotherapy regimens for advanced, recurrent, or metastatic endometrial cancer
•History of myocardial infarction, acute inflammatory heart disease, unstable angina, or uncontrolled arrhythmia within the past 6 months.
•Impaired cardiac function defined as left ventricular ejection fraction (LVEF) \< 50 % (or below the study site's lower limit of normal) as measured by MUGA or ECHO. Planned concomitant use of potentially cardiotoxic medication.
•Previous anthracycline-based chemotherapy.
•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, doxorubicin 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 4 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. Note: Palliative radiotherapy within 2 weeks prior to study is allowed provided that the site being treated is not subsequently used as a target lesions as per RECIST v.1.1 for the purpose of assessing tumor response on trial.

Arms & Interventions

A

Doxorubicin 60 mg/kg IV over 30 minutes on day 1 every 3 weeks up to 9 cycles in combination with Pembrolizumab (MK-3475) 200 mg IV Q3W

Intervention: Pembrolizumab

Outcomes

Primary Outcomes

PFS rate at 6 months according to RECIST 1.1 criteria

Time Frame: 6 months

To evaluate the efficacy of anti-PD1 blockade with pembrolizumab in combination with immunogenic chemotherapy with doxorubicin in patients with recurrent endometrial cancer in terms of patients who survived progression free (PFS) at least 6 months.

Secondary Outcomes

To determine median PFS and ORR according to RECIST 1.1 criteria.(Through study completion, an average of 3 years)
To determine median PFS and ORR according to RECIST 1.1 criteria in different genomic-TCGA subgroups(Through study completion, an average of 3 years)
To determine PFS rate at 6 months according to RECIST 1.1 criteria in the different groups by the genomic-The Cancer Genome Atlas (TCGA) classification; namely POLE, MSI, and Microsatellite Stable (MSS)(6 months)
To determine median OS and OS rate(At 1, and 2-years)
To evaluate median OS and OS rate at 1, and 2-years according to genomic-TCGA classification.(Through study completion, an average of 3 years)
To evaluate DoR, defined as the time from first documented evidence of complete response (CR)or partial response (PR) until disease progression or death due to any cause, whichever occurs first(Through study completion, an average of 3 years)
Number and grade of AEs, ECIs, SAEs, fatal SAEs, and laboratory changes that are Treatment-Related Adverse Events as Assessed by CTCAE v4.0(Through study completion, an average of 3 years)