About Bolder Science

Our mission is to provide healthcare professionals with unbiased clinical research information, easily.

Currently, you can access the following clinical trials being conducted worldwide:

359,057 studies
in
219 countries
Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/21/2021.
This website is for US healthcare professionals

Log In to Bolder Science

or

Don't have an account? Sign Up

Please enter your email address.

You will receive a link to create a new password via email.

Log In

Create an Account

or
(optional) ?

Welcome, !

Please complete the following 4 questions to ensure you receive the information that best suits your needs.

Clinical Trials of Interest

When I’m looking for information on clinical trials, I usually am interested in...

finding clinical trials in which to enroll my patients

Rarely Often

finding newly launched clinical trials (for all phases)

Rarely Often

updates on status changes for clinical trials

Rarely Often

pipeline molecules

Rarely Often

Drug Interventions

Enter up to 3 drug interventions you are currently interested in:

Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/21/2021.

Study of Cabozantinib as 2nd Line Treatment in Subjects With Locally Advanced or Metastatic Renal Cell Carcinoma (RCC) With a Clear-Cell Component Who Progressed After 1st Line Treatment With Checkpoint Inhibitors

Clinicaltrials.gov identifier NCT03945773

Recruitment Status Recruiting

First Posted May 10, 2019

Last update posted August 28, 2020

Study Description

Brief summary:

The overall objective of this study is to evaluate the efficacy and safety of cabozantinib as 2nd line treatment in subjects with unresectable, locally advanced or metastatic RCC with a clear-cell component, who progressed after prior Checkpoint Inhibitors (CPI) therapy with ipilimumab and nivolumab in combination or CPI combined with Vascular Endothelial Growth Factor (VEGF)-targeted therapy.

  • Condition or Disease:Locally Advanced or Metastatic Renal Cell Carcinoma
  • Intervention/Treatment: Drug: Cabozantinib
  • Phase: Phase 2
Detailed Description

N/A

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 250 participants
  • Allocation: Non-Randomized
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: A Phase II, Multicentre, Open-label Study of Cabozantinib as 2nd Line Treatment in Subjects With Unresectable, Locally Advanced or Metastatic Renal Cell Carcinoma With a Clear-Cell Component Who Progressed After 1st Line Treatment With Checkpoint Inhibitors.
  • Actual Study Start Date: January 2020
  • Estimated Primary Completion Date: February 2022
  • Estimated Study Completion Date: January 2023
Arms and interventions
Arm Intervention/treatment
Experimental: Cohort A
Subjects who radiographically progressed after one prior line by CPI therapy with ipilimumab and nivolumab.
Drug: Cabozantinib
Oral tablets of 60mg, 40mg and 20 mg.
Experimental: Cohort B
Subjects who radiographically progressed after one prior line by CPI therapy combined with VEGF-targeted therapy.
Drug: Cabozantinib
Oral tablets of 60mg, 40mg and 20 mg.
Outcome Measures
  • Primary Outcome Measures: 1. Objective response rate (ORR) [ Time Frame: up to 42 months ]
    Assesses by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 assessed by Independent Central review
  • Secondary Outcome Measures: 1. Objective response rate (ORR) [ Time Frame: up to 42 months ]
    Assesses by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 assessed by the Investigator
  • 2. Time to response (TTR) [ Time Frame: Every 12 weeks up to 42 months ]
    Assesses by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 assessed by the Investigator and Independent Central review
  • 3. Duration of response (DOR) [ Time Frame: Every 12 weeks up to 42 months ]
    Assesses by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 assessed by the Investigator and Independent Central review
  • 4. Disease control rate (DCR) [ Time Frame: Every 12 weeks up to 42 months ]
    Assesses by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 assessed by the Investigator and Independent Central review
  • 5. Progression-free survival (PFS) [ Time Frame: Every 12 weeks up to 42 months ]
    Assesses by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 assessed by the Investigator and Independent Central review
  • 6. Change in disease-related symptoms [ Time Frame: Every 12 weeks up to 42 months ]
    Assessed by the Functional Assessment of Cancer Therapy-Kidney Cancer Symptom Index (FKSI-DRS) questionnaire.
  • 7. Overall survival (OS) [ Time Frame: Every 12 weeks starting after End of Study Treatment visit (30 days after the last dose) until the subject expires or the end of the study (18 months after the last subject received the first cabozantinib dose), whichever occurs first. ]
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

All subjects must fulfil all the following criteria to be included in the study:

1. Subjects must provide a signed informed consent prior to any study-related procedures;

2. Male or female subjects must be aged ≥18 years on the day the informed consent is
signed;

3. Subjects must have histologically confirmed unresectable, locally advanced (defined as
disease not eligible for curative surgery or radiation therapy) or metastatic RCC with
a clear-cell carcinoma component;

4. Subjects must have radiographic disease progression, according to Investigator's
judgement following 1st line treatment with CPI (ipilimumab plus nivolumab) (Cohort A)
or CPI in combination with VEGF-targeted therapy (Cohort B);

5. Subjects present ≥1 target lesion according to RECIST 1.1 per Investigator;

6. Subjects should have Eastern Cooperative Oncology Group (ECOG) status 0-1;

7. Subjects with treated brain metastases are eligible if metastases have been shown to
be stable as per Investigator's judgement;

8. Subjects must have adequate organ and marrow function, based upon meeting all of the
following laboratory criteria within 15 days before baseline:

1. Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L).

2. Platelets ≥ 100,000/mm3 (≥ 100 GI/L).

3. Haemoglobin ≥ 9 g/dL (≥ 90 g/L).

4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 × upper limit of normal (ULN). 5. Total bilirubin ≤ 1.5 × ULN. For subjects with Gilbert's disease ≤ 3 mg/dL (≤ 51.3 μmol/L). 6. Fasting serum triglycerides ≤ 2.5 × ULN AND total cholesterol ≤ 300 mg/dL (≤ 7.75 mmol/L). Lipid-lowering medication is allowed. 7. Serum creatinine ≤ 2.0 × ULN or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault equation 8. Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine or 24-hour urine protein 140 mm Hg
systolic or >90 mm Hg diastolic pressure) despite optimal antihypertensive
treatment;

3. Stroke (including transient ischaemic attack (TIA)), myocardial infarction (MI)
or other ischaemic event, or thromboembolic event (e.g. deep venous thrombosis,
pulmonary embolism) within 6 months before screening;

4. History of risk factors for torsades de pointes (e.g., long QT syndrome);

7. Is receiving concomitant anticoagulation with oral anticoagulants (e.g. warfarin,
direct thrombin and Factor Xa inhibitors) or platelet inhibitors (e.g. clopidogrel);
Note: Low-dose aspirin for cardioprotection (per local applicable guidelines) and low
dose, low molecular weight heparin (LMWH) are permitted.

8. Has a gastrointestinal (GI) disorder including those associated with a high risk of
perforation or fistula formation:

(a) Tumours invading the GI tract, active peptic ulcer disease, inflammatory bowel
disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute
pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet
obstruction; b) Abdominal fistula, GI perforation, bowel obstruction, or
intra-abdominal abscess within 6 months before screening; Note: Complete healing of an
intra-abdominal abscess must have been confirmed before screening

9. Presents a corrected QT (QTc) interval calculated by the Fridericia formula (QTcF) >
500 msec within 1 month prior to baseline; Note: If a single ECG shows a QTcF with an
absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must
be performed within 30 min after the initial ECG, and the average of these three
consecutive results for QTcF will be used to determine eligibility

10. Presents clinically significant haematuria, hematemesis, or haemoptysis of >0.5
teaspoon (2.5 mL) of red blood, or other history of significant bleeding (e.g.

pulmonary haemorrhage) within 3 months before screening;

11. Presents cavitating pulmonary lesion(s) or known endobronchial disease manifestation;

12. Presents lesions invading major pulmonary blood vessels;

13. Has been diagnosed with other clinically significant disorders such as:

1. Serious nonhealing wound/ulcer/bone fracture;

2. Malabsorption syndrome;

3. Free thyroxine 4 (FT4) outside the laboratory normal reference range;

4. Uncompensated/symptomatic hypothyroidism;

5. Moderate to severe hepatic impairment (Child-Pugh B or C);

6. Requirement for haemodialysis or peritoneal dialysis;

7. History of solid organ transplantation;

14. Has a predicted life expectancy of less than 3 months;

15. Has had prior surgery within 4 weeks prior to baseline. Note: If the subject has
undergone major surgery, complete wound healing must have occurred 1 month prior to
baseline

16. Has had palliative radiation therapy for bone within 2 weeks or for radiation fields
including viscera within 4 weeks prior to baseline. Note: Resolution/healing of side
effects must be complete prior to baseline;

17. Has a history of another active malignancy within 3 years from screening except for
locally curable cancers that have been apparently cured, such as low-grade thyroid
carcinoma, prostate cancer not requiring treatment (Gleason Grade ≤6), basal or
squamous cell skin cancer, superficial bladder cancer, in situ melanoma, in situ
prostate, cervix or breast carcinoma or other treated malignancies with <5% chance of relapse according to the Investigator; 18. Has a history of allergy to study treatment components or agents with a similar chemical structure or any excipient used in the formulation as listed in the Summary of Product Characteristics (SmPC) document; 19. Has rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded; 20. Has a serious medical or psychiatric condition that renders the subject unable to understand the nature, scope and possible consequences of the study, and/or presents an uncooperative attitude; 21. Is pregnant or breastfeeding. A β-human chorionic gonadotrophin (HCG) serum pregnancy test will be performed up to 7 days prior to baseline for all female subjects of childbearing potential (i.e. less than or equal to 2 years post-menopause and not surgically sterile); 22. Is likely to require treatment during the study with drugs that are not permitted by the study protocol; 23. Has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardise the subject's safety

Contacts and Locations
Contacts

Contact: Ipsen Recruitment Enquiries clinical.trials@ipsen.com

Locations
Show 33 Study Locations
Sponsors and Collaborators

Ipsen

Investigators

Study Director: Ipsen Medical Director Ipsen

More Information
  • Responsible Party: Ipsen
  • ClinicalTrials.gov Identifier: NCT03945773 History of Changes
  • Other Study ID Numbers: F-FR-60000-023, 2018-002820-18
  • First Posted: May 10, 2019 Key Record Dates
  • Last Update Posted: August 28, 2020
  • Last Verified: August 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: Yes
  • Plan Description: Where patient data can be anonymized, Ipsen will share all individual participant data that underlie the results reported in the published journal article with qualified researchers who provide a valid research question. Study documents, such as the study protocol and clinical study report, are not always available
  • Time Frame: Data are available beginning 6 months and ending 5 years after the publication of the findings in a journal; after this time, only raw data may be available.
  • Access Criteria: Proposals should be submitted to DataSharing@ipsen.com and will be assessed by a scientific review board.
  • Studies a U.S. FDA-regulated Drug Product: No
  • Studies a U.S. FDA-regulated Device Product: No
  • Product Manufactured in and Exported from the U.S.: Yes
  • Additional relevant MeSH terms: Carcinoma Carcinoma, Renal Cell