Phase II Study on Carboplatin-Paclitaxel-Pembrolizumab in Neoadjuvant Treatment of Locally Advanced Cervical Cancer
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Locally Advanced Cervical Cancer
- Sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- 2-years Progression-free survival
- Last Updated
- 4 years ago
Overview
Brief Summary
Single arm multicenter phase II trial evaluating the role of Pembrolizumab in combination to Carboplatin-Paclitaxel chemotherapy in locally advanced cervical cancer patients.
Detailed 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.
Investigators
Eligibility Criteria
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.
- •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.
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-Guérin (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.
Arms & Interventions
Carboplatin-Paclitaxel-Pembrolizumab
Patients 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 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.
Intervention: Pembrolizumab
Carboplatin-Paclitaxel-Pembrolizumab
Patients 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 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.
Intervention: Carboplatin
Carboplatin-Paclitaxel-Pembrolizumab
Patients 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 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.
Intervention: Taxol
Outcomes
Primary Outcomes
2-years Progression-free survival
Time Frame: 42 months
The combination of Pembrolizumab-chemotherapy is expected to increase 2-years progression free survival with respect to historical controls.
Secondary Outcomes
- Clinical Response rate(42 months)
- Overall survival(42 months)
- Pathologic optimal response(42 months)
- Adverse events(42 months)
- Quality of life(42 months)
- Immune-related gene signatures associated with response or resistance to immune checkpoint blockade(42 months)