Carboplatin-Paclitaxel-Pembrolizumab in Neoadjuvant Treatment of Locally Advanced Cervical Cancer

  • STATUS
    Recruiting
  • End date
    Sep 1, 2023
  • participants needed
    45
  • sponsor
    Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Updated on 2 September 2021

Summary

Single arm multicenter phase II trial evaluating the role of Pembrolizumab in combination to Carboplatin-Paclitaxel chemotherapy in locally advanced cervical cancer patients.

Description

Patients with stage IB2-IIB cervical cancer will be treated with 3 cycles of neoadjuvant Carboplatin-Paclitaxel chemotherapy (Carboplatin AUC 5 d1 q 21+ Paclitaxel 175 mg/mq d1 q 21)+ Pembrolizumab (200 mg flat dose every 3 weeks).

After 3 cycles of neo-adjuvant platinum-based chemotherapy patients non progressing will undergo radical surgery.

After surgery, patients presenting with high risk factors (positive lymphnodes, positive parametria, positive surgical margins or at least 2 of the following risk factor between tumor diameter >3 cm, LVSI, stromal infiltration >1/3) will receive 3 cycles of adjuvant Carboplatin-Paclitaxel chemotherapy + Pembrolizumab in combination and maintenance with Pembrolizumab 200 mg every 3 weeks until progression or unacceptable toxicity or patient consent withdrawal for up to 35 cycles.

Details
Condition Locally Advanced Cervical Cancer
Treatment carboplatin, Pembrolizumab, Taxol
Clinical Study IdentifierNCT04238988
SponsorFondazione Policlinico Universitario Agostino Gemelli IRCCS
Last Modified on2 September 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of FIGO Stage IB2-IIB cervical cancer will be enrolled in this study. Squamous, adenocarcinoma and adenosquamous histotypes are admitted
PDL1+>1% of cell by IHC evaluation in tumor cells
Eligible for carboplatin and paclitaxel chemotherapy in accordance with local standards of care
A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies
Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 4 months after the end of treatment
The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue
Note: If submitting unstained cut slides, newly cut slides should be submitted
to the testing laboratory within 14 days from the date slides are cut
\. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0
to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of
treatment initiation
\. Have adequate organ function as defined in the following table (Table 1)
Specimens must be collected within 10 days prior to the start of study
treatment
\. No previous systemic chemotherapy or radiation therapy for cervical
cancer

Exclusion Criteria

A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment initiation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137)
Has received prior radiotherapy within 2 weeks of start of study treatment for palliative intent. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Gurin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist) are live attenuated vaccines and are not allowed
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
Note: Participants who have entered the follow-up phase of an investigational
study may participate as long as it has been 4 weeks after the last dose of
the previous investigational agent
\. Has a diagnosis of immunodeficiency or is receiving chronic systemic
steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or
any other form of immunosuppressive therapy within 7 days prior to the first
dose of study drug
\. Has a known additional malignancy that is progressing or has required
active treatment within the past 3 years. Note: Participants with basal cell
carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in
situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone
potentially curative therapy are not excluded
\. Has known active CNS metastases and/or carcinomatous meningitis
Participants with previously treated brain metastases may participate provided
they are radiologically stable, i.e. without evidence of progression for at
least 4 weeks by repeat imaging (note that the repeat imaging should be
performed during study screening), clinically stable and without requirement
of steroid treatment for at least 14 days prior to first dose of study
treatment
\. Has severe hypersensitivity (Grade 3) to Pembrolizumab and/or any of its
excipients
\. 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
has current pneumonitis
\. Has an active infection requiring systemic therapy
\. Has a known history of Human Immunodeficiency Virus (HIV)
\. Has a known history of Hepatitis B (defined as Hepatitis B surface
antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV
RNA is detected) infection
\. Has a known history of active TB (Bacillus Tuberculosis)
\. Has a history or current evidence of any condition, therapy, or
laboratory abnormality that might confound the results of the study, interfere
with the subject's participation for the full duration of the study, 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 or father children
within the projected duration of the study, starting with the screening visit
through 120 days after the last dose of trial treatment
\. History of cerebrovascular accident, pulmonary embolism or untreated
grade 3 deep venous thrombosis (DVT) within the past 6 months
\. NCI CTCAE (version 5.0) grade 2 enteritis
\. History of myocardial infarction, unstable angina, subarachnoid
haemorrhage, stroke or transient ischaemic attack within 6 months before first
dose of study drug
\. Clinically significant active cardiovascular disease (e.g., New York
Heart Association class II or greater congestive heart failure [CHF], aortic
aneurysm)
\. Serious cardiac arrhythmia requiring medication. This does not include
asymptomatic atrial fibrillation with controlled ventricular rate
\. Significant vascular disease (e.g., aortic aneurysm requiring surgical
repair or recent arterial thrombosis) within 6 months before study enrolment
\. Pre-existing NCI CTCAE (version 5.0) grade 2 peripheral neuropathy
\-
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