A Phase II Trial of Pembrolizumab and Ramucirumab in Patients With Progressive Transitional Cell Carcinoma After Treatment With an Immune Checkpoint Inhibitor
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab and Ramucirumab
- Conditions
- Transitional Cell Carcinoma
- Sponsor
- Yale University
- Locations
- 1
- Primary Endpoint
- Overall response rate (ORR)
- Status
- Withdrawn
- Last Updated
- 4 years ago
Overview
Brief Summary
This study is designed to evaluate response and survival of treatment with the combination of pembrolizumab and ramucirumab in patients with progressive metastatic TCC after immune checkpoint inhibitor treatment.
Detailed Description
This is a phase II, non-randomized single center study designed to evaluate response and survival of treatment with the combination of pembrolizumab and ramucirumab in patients with progressive metastatic TCC after immune checkpoint inhibitor treatment. The primary and secondary objectives are as follows: Primary: * Objective: To evaluate overall response rate (ORR) in patients treated with pembrolizumab and ramucirumab * Hypothesis: The ORR will be ≥15% greater than the historical rate in published literature of patients treated with pembrolizumab alone Secondary Objectives: * Objective: To evaluate progression free survival (PFS) in patients treated with pembrolizumab and ramucirumab * Hypothesis: The PFS will be ≥15% greater than the historical rate in published literature of patients treated with pembrolizumab alone * Objective: To evaluate overall survival (OS) in patients treated with pembrolizumab and ramucirumab * Hypothesis: The OS will be ≥15% greater than the historical rate in published literature of patients treated with pembrolizumab alone * Objective: To evaluate differences in ORR, PFS and OS in patients treated with pembrolizumab and ramucirumab stratified by Bellmunt criteria. * Hypothesis: Patients with high Bellmunt criteria scores will have lower rates of ORR, PFS and OS.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed transitional cell carcinoma of the urothelium (bladder, urethra, or renal pelvis). Patients with mixed pathology are eligible only if they have predominantly transitional cell tumor based on local pathology review.
- •Unresectable, locally advanced or metastatic disease.
- •Documented disease progression by RECIST 1.1 criteria to at least one prior line of systemic therapy and no more than three. Prior therapy for advanced disease must include an immune checkpoint inhibitor. Prior therapy in an adjuvant or neoadjuvant setting is not considered as a prior line of systemic chemotherapy, unless patient has rapidly progressed as defined by ≤ 6 months of last dose in this setting. If it is ≤ 6 months, it will be regarded as a prior line of treatment. Prior treatment with intravesicular chemotherapy, bacillus Calmette -Guérin (BCG), or platinum given as a radiation-sensitizing agent will not be considered as a systemic line of treatment.
- •A brain scan via CT with contrast or MRI is to be performed to confirm absence of intracranial metastasis.
- •The presence of measurable disease based on the Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as determined by the site study team. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- •a. Measurable disease must still be present after pretreatment core-needle or excisional biopsy.
- •Provided signed informed consent and are amenable to compliance with protocol schedules and testing.
- •Provided tissue for biomarker analysis from a newly obtained core or excisional biopsy of a tumor lesion using a non-significant risk procedure prior to enrollment. Repeat samples may be required if adequate tissue is not provided.
- •ECOG Performance Status of 0 or
- •Age: 18 years of age or older on day of signing consent.
Exclusion Criteria
- •Have non-measurable disease
- •Have known brain metastases, uncontrolled spinal cord compression, or leptomeningeal disease
- •Have received ≥3 lines of prior systemic anticancer therapy for advanced disease in urothelial cancer patients
- •Have a serious illness or medical condition(s) including, but not limited to, the following:
- •Diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after evaluation by the Sponsor-Investigator.
- •Active autoimmune disease that has required systemic treatment in past 2 years (that is, with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (for example, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •Received a prior autologous or allogeneic organ or tissue transplantation
- •Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- •History of interstitial lung disease
- •Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness
Arms & Interventions
Pembrolizumab and Ramucirumab
Patients with progressive transitional cell carcinoma after treatment with an immune checkpoint inhibitor will receive Pembrolizumab and Ramucirumab.
Intervention: Pembrolizumab and Ramucirumab
Outcomes
Primary Outcomes
Overall response rate (ORR)
Time Frame: Up to 24 months
The objective overall response rate (ORR) is the proportion of enrolled patients who have received any amount of either study drug, have at least 1 post baseline tumor image, and achieve a best overall response of complete response (CR) or partial response (PR). The ORR will be assessed based on RECIST 1.1 and irRECIST.
Secondary Outcomes
- Progression free survival (PFS)(Up to 24 months)
- Overall survival (OS)(Up to 24 months)