Phase II trial of Pembrolizumab in combination with Doxorubicin in Advanced, Recurrent or Metastatic Endometrial Cancer (TOPIC)
- Conditions
- Advanced, Recurrent or Metastatic Endometrial CancerMedDRA version: 12.0 Level: HLGT Classification code 10007129 Term: Cancer-related morbidities System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-002824-26-ES
- Lead Sponsor
- Vall d' Hebron Institute of Oncology (VHIO)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 51
1. 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
2. Be =18 years of age on day of signing informed consent.
3. 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.
4. 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.
5. 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.
6. 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). 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 1.
7. Have a performance status of 0 or 1 on the ECOG Performance Scale.
8. Demonstrate adequate organ function as defined in Table 2, all screening labs should be performed within 7 days of treatment initiation.
9. 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11
1.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.
2.Receipt of 2 or more prior chemotherapy regimens for advanced, recurrent, or metastatic endometrial cancer
3.History of myocardial infarction, acute inflammatory heart disease, unstable angina, or uncontrolled arrhythmia within the past 6 months.
4.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.
5.Previous anthracycline-based chemotherapy.
6.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.
7.Has a known history of active TB (Bacillus Tuberculosis)
8.Hypersensitivity to pembrolizumab, doxorubicin or any of its excipients.
9.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.
10.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.
11.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.
12.Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
13.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.
14.Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
15.Has an active infection requiring systemic therapy.
16.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.
17.Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
18.Is pregnant or breastfeeding, or expecting to conceive 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.
19.Has previously participated in any other pembrolizumab (MK-3475) trial, or received prior
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method