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Transitional Cell CarcinomaPhase 2NCT04179110

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

A Phase 2 study testing Pembrolizumab and Ramucirumab in people with Transitional Cell Carcinoma, run by Yale University at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Transitional Cell Carcinoma
What is being tested?
Pembrolizumab and Ramucirumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
18 Sep 2020to 15 Jun 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Measurable disease must still be present after pretreatment core-needle or excisional biopsy.
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  • 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.
  • Resolution, except where otherwise stated in the inclusion criteria, of all clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy to Grade ≤1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 (v 5.0)
  • For male patients, are sterile (including vasectomy confirmed by post-vasectomy semen analysis) or agree to use a reliable method of birth control and to not donate sperm during the study and for at least 120 days following the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
  • For female patients, are surgically sterile, are postmenopausal, or agree to use a highly effective method of birth control (2 methods preferred) during the study and for 120 days following the last dose of study treatment.
  • If female and of childbearing potential, must have a negative serum or urine pregnancy test within 7 days prior to enrollment.
  • Note: Non-childbearing potential (by other than medical reasons). Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.

Who cannot join

  • 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.
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  • 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
  • The patient is pregnant or breast-feeding.
  • The patient has radiologically documented evidence of major blood vessel invasion or encasement by cancer.
  • Known psychiatric or substance abuse disorders
  • Known allergy or hypersensitivity reaction to any of the treatment components
  • History of hematologic malignancy, malignant primary brain tumor, malignant sarcoma, or other malignant priory solid tumor not under study, except:
  • no evidence of that disease for 5 years
  • adequately treated non-melanoma skin cancer
  • curatively treated cervical carcinoma in situ or other noninvasive carcinoma or in situ neoplasm
  • Have received any previous systemic therapy (including investigational agents) targeting VEGF/VEGF receptor. Prior therapy with anti-CD137 or anti-CTLA-4 antibody is permitted.
  • Have received a live vaccine within 30 days prior to enrollment Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  • Have received transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], or recombinant erythropoietin) within 4 weeks prior to Cycle 1 Day 1
  • Have a significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment
  • Have experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to enrollment
  • Have experienced any Grade 3 or 4 venous thromboembolic event (VTE) that is considered by the investigator to be life threatening or that is symptomatic and not adequately treated by anticoagulation therapy, within 6 months prior to enrollment
  • Have a history of gastrointestinal perforation and/or fistula within 6 months prior to enrollment or risk factors for perforation.
  • Have a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection, either condition with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea
  • Have uncontrolled hypertension, as defined as Grade >2 CTCAE Version 5.0 (clinically, the patient continues to experience elevated blood pressure [systolic >160 mmHg and/or diastolic >100 mmHg] despite medications)
  • Are receiving chronic therapy with any of the following within 7 days prior to enrollment (note: aspirin use at doses up to 325 mg/day is permitted):
  • nonsteroidal anti-inflammatory agents (NSAIDs; such as indomethacin, ibuprofen, naproxen, or similar agents)
  • other anti-platelet agents (such as clopidogrel, ticlopidine, dipyridamole, or anagrelide)
  • Have had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment
  • Have an elective or a planned major surgery during the course of the trial or has undergone major surgery within 28 days prior to enrollment, or central venous access device placement within 7 days prior to enrollment. Note: If patient received major surgery, the patient must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Have had chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks and/or monoclonal antibody treatment within 4 weeks prior to enrollment or not recovered (that is, ≤ Grade 1 or at baseline) from previously administered agents. Note: Neuropathy (≤ Grade 2) or nonserious and nonlife-threatening toxicities, such as alopecia, altered taste, or nail changes, are an exception to this criterion. Note: Palliative radiotherapy during the study, if clinically indicated, can be considered after consultation with the medical monitor.
  • Are currently enrolled in a clinical trial involving an investigational product or non-approved use of a drug, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study or discontinued study drug within 28 days or 5 half-lives of the drug, whichever is longer, prior to enrollment. Patients participating in surveys or observational studies are eligible to participate in this study.
  • Are or have an immediate family member (for example, spouse, parent/legal guardian, sibling, or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective institutional review board (IRB) approval (by chair or designee) is given allowing exception to this criterion for a specific patient
  • Have radiographic evidence of intratumor cavitation
  • Have a history of gross hemoptysis (defined as bright red blood or ≥1/2 teaspoon) within 2 months prior to enrollment
  • Have pleural effusion, pericardial fluid, or ascites requiring drainage every other week or more frequently
  • Have superior vena cava syndrome
  • Have preexisting idiopathic pulmonary fibrosis as evidenced by CT scan/X-ray at baseline; have or had any disease of acute lung injury, idiopathic pulmonary fibrosis, or pneumoconiosis evident on an X-ray; have or had any disease of radiation pneumonia or drug-induced pneumonia.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Unable to have a pretreatment core-needle or excisional biopsy.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Yale University

    New Haven, Connecticut, 06520

Other trials in United States

About this study

Official title: A Phase II Trial of Pembrolizumab and Ramucirumab in Patients With Progressive Transitional Cell Carcinoma After Treatment With an Immune Checkpoint Inhibitor

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.

Read the 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.
Being tested
Pembrolizumab and Ramucirumab
Medical subject headings
Carcinoma, Transitional Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pembrolizumab and RamucirumabDrug

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

Study groups in NCT04179110
Study groupRoleWhat they receive
Pembrolizumab and RamucirumabExperimentalPatients with progressive transitional cell carcinoma after treatment with an immune checkpoint inhibitor will receive Pembrolizumab and Ramucirumab.
Receives: Drug: Pembrolizumab and Ramucirumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 24 months

Secondary outcomes (2)

  1. Progression free survival (PFS)

    Progression-free survival (PFS) is defined as the time from the date of first study treatment until the date of the first observed radiographically documented PD or death due to any cause, whichever is earlier.

    Measured: Up to 24 months

  2. Overall survival (OS)

    Overall survival (OS), including 1- and 2- year survival rates, is determined from the date of first study treatment until death due to any cause. If the patient was alive at the data inclusion cutoff date for the analysis (or was lost to follow-up), OS will be censored on the last date the patient was known to be alive.

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Nov 2019
  2. Study start18 Sep 2020
  3. Primary completion15 Dec 2022 (estimated)
  4. Study completion15 Jun 2023 (estimated)

Why it stopped: Funding was withdrawn prior to first enrollment.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04179110
Sponsor's protocol ID
2000022801
Status last verified
Feb 2022
First submitted
25 Nov 2019
Last updated
22 Feb 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Ramucirumab in people with Transitional Cell Carcinoma, run by Yale University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 22 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (ORR) (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04179110.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2022.

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