Study of Pembrolizumab and Ramucirumab in Pts With Progressive TCC After Treatment With an Immune Checkpoint Inhibitor

NCT04179110 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 2000022801
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Transitional Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  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.

  Up to 24 months

Secondary Outcomes (2)

• Progression free survival (PFS)

  Up to 24 months

• Overall survival (OS)

  Up to 24 months

Study Arms (1)

Pembrolizumab and Ramucirumab

EXPERIMENTAL

Patients with progressive transitional cell carcinoma after treatment with an immune checkpoint inhibitor will receive Pembrolizumab and Ramucirumab.

Drug: Pembrolizumab and Ramucirumab

Interventions

Pembrolizumab and Ramucirumab DRUG

Patients will receive Pembrolizumab 200 mg \& Ramucirumab 10 mg/kg every 3 weeks.

Pembrolizumab and Ramucirumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 1.
• Age: 18 years of age or older on day of signing consent.
• Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
• The patient's urinary protein is ≤1+ on dipstick or routine urinalysis (UA; if urine dipstick or routine analysis is ≥2+, a 24-hour urine collection for protein must demonstrate \<1000 mg of protein in 24 hours to allow participation in this protocol)
• Adequate organ function, as defined in the table below, with all screening labs performed within 14 days of treatment initiation:
• Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin. If receiving warfarin, the patient must have an INR ≤ 3.0 and no active bleeding (i.e., no bleeding within 14 days prior to first dose of study treatment) or pathological condition present that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices). Patients on anticoagulation therapy with unresected primary tumors or local tumor recurrence following resection are not eligible.
• An anticipated life expectancy of ≥3 months.

You may not qualify if:

• 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
• Known active Hepatitis B or Hepatitis C infection
• Liver cirrhosis at a level of Child-Pugh B (or worse)
• Liver cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis.
• Have a serious cardiac condition, such as congestive heart failure; unstable angina pectoris; myocardial infarction within the last 6 months; valvulopathy that is severe, moderate, or deemed clinically significant; or arrhythmias that are symptomatic or require treatment (not including patients with rate-controlled atrial fibrillation)
• Active or uncontrolled clinically serious infection

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale University

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

pembrolizumab; Ramucirumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Michael Hurwitz, PhD, MD

  Assistant Professor of Medicine (Medical Oncology) Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2019
• First Posted: November 27, 2019
• Study Start: September 18, 2020
• Primary Completion: December 15, 2022
• Study Completion: June 15, 2023
• Last Updated: February 22, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)