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Safety and Efficacy of Everolimus in Metastatic Renal Cell Carcinoma After Failure of First Line Therapy With Sunitinib or Pazopanib (MACS1760)

This study is currently recruiting participants.
Verified February 2013 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01514448
First received: January 17, 2012
Last updated: February 25, 2013
Last verified: February 2013
History of Changes
  Purpose

Patients with metastatic renal cell carcinoma (mRCC) who have failed first-line therapy with sunitinib or pazopanib will be treated with everolimus. Efficacy and safety of everolimus will be evaluated in theses patients.


Condition Intervention Phase
Metastatic Renal Cell Carcinoma (mRCC)
 Drug: Everolimus
 Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Single Arm Trial to Evaluate Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus After Failure of First Line Therapy With Sunitinib or Pazopanib

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Rate of patients progression-free after 6 months of treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Primary endpoint is proportion of patients progression-free by month 6 after starting everolimus treatment. A 'responder' will be defined as a subject without progression by month 6 whereas a 'non-responder' will be defined as a subject with progressive disease by month 6. The primary variable will be derived from radiologic tumor assessments according to RECIST 1.1.


Secondary Outcome Measures:
  • Progression-free survival as the time interval between first intake of everolimus and first documented disease progression or death due to any cause [ Time Frame: Baseline, Every 3 months ] [ Designated as safety issue: No ]
    Progression-free survival is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment

  • Overall survival of patients treated with everolimus after failure of first-line sunitinib or pazopanib therapy [ Time Frame: Baseline, every 28 days ] [ Designated as safety issue: No ]
    Overall survival (OS) is defined as the time from date of start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last contact.

  • Overall response rate in patients treated with everolimus after failure of first-line sunitinib or pazopanib therapy [ Time Frame: Baseline, every 3 months ] [ Designated as safety issue: No ]
    Investigator's best overall response rate (ORR) is the proportion of patients with a best overall response of complete response (CR) or partial response (PR) by month 6. ORR will be assessed according to RECIST 1.1 criteria.

  • Duration of response in patients treated with everolimus after failure of first-line sunitinib or pazopanib therapy [ Time Frame: Baseline, Every 3 months ] [ Designated as safety issue: No ]
    The duration of overall response (CR or PR) is defined as the time from the first occurrence of a confirmed CR or PR (as per investigator assessment according to RECIST 1.1) until the date of the first documented disease progression or death due to underlying cancer. If a patient has not had an event or when they receive any further anticancer therapy, duration of overall response is censored at the date of last adequate tumor assessment. Duration of response will be displayed only for patients whose best overall response was CR or PR

  • Safety of everolimus after failure of first-line sunitinib or pazopanib therapy [ Time Frame: Baseline, Every 28 days ] [ Designated as safety issue: No ]
    The assessment of safety will be based mainly on frequency of adverse events and on the number of laboratory values that fall outside of pre-determined ranges. Other safety data (e.g., electrocardiogram, vital signs) will be considered as appropriate. All safety data will be listed. The safety summary tables will only include assessments collected no later than 28 days after study treatment discontinuation. All safety assessments will be listed and those collected later than 28 days after study treatment discontinuation will be flagged.


Estimated Enrollment: 36
Study Start Date: May 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus
62 evaluable patients who have progressed during or after first-line therapy with sunitinib or pazopanib will be enrolled: patients previously treated with first-line sunitinib (group 1) and 31 patients previously treated with first-line pazopanib (group 2). The protocol consists of two independent single-arm, single-stage trial run in the following groups: group 1 (patients previously treated with first-line sunitinib for mRCC) and group 2 (patients previously treated with first-line pazopanib for mRCC). The efficacy and safety of everolimus will be analyzed separately in each group. Patients who meet all inclusion and none of the exclusion criteria will be treated with everolimus 10 mg daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawn consent.
 Drug: Everolimus
Everolimus will be prescribed by the investigator. Everolimus will be used as commercially available tablets of 10 mg strength and 5 mg strength for dose modifications. On the first day of each cycle, patients will receive a prescription of an adequate drug supply for self-administration at home. The investigator must emphasize compliance and will instruct the patient to take everolimus exactly as prescribed.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with advanced renal cell carcinoma of a histological or cytological confirmation of clear cell renal carcinoma.
  • Progression during or after a treatment with sunitinib or pazopanib given in a 1st line treatment situation for mRCC.
  • Patients scheduled for treatment with everolimus.
  • Patients with at least one measurable lesion at baseline.

Exclusion Criteria:

  • Patients who have received >1 prior systemic treatment for their metastatic RCC. Prior systemic treatment in an adjuvant setting is allowed.
  • Patients who have previously received systemic mTOR inhibitors (e.g. sirolimus, temsirolimus, everolimus).
  • Patients who are using other investigational agents or who had received investigational drugs ≤ 2 weeks prior to study treatment start.
  • Patients unwilling or unable to comply with the protocol.

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01514448

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

Locations
Germany
Novartis Investigative Site Withdrawn
Berlin, Germany, 13055
Novartis Investigative Site Recruiting
Berlin, Germany, 12107
Novartis Investigative Site Recruiting
Goslar, Germany, 38642
Novartis Investigative Site Recruiting
Hof, Germany, 95028
Novartis Investigative Site Recruiting
Kassel, Germany, 34125
Novartis Investigative Site Recruiting
Koeln, Germany, 50671
Novartis Investigative Site Recruiting
Langen, Germany, 63225
Novartis Investigative Site Not yet recruiting
Leipzig, Germany, 04357
Novartis Investigative Site Recruiting
Magdeburg, Germany, 39120
Novartis Investigative Site Recruiting
Muenster, Germany, 48149
Novartis Investigative Site Recruiting
Ravensburg, Germany, 88214
Novartis Investigative Site Not yet recruiting
Velbert, Germany, 42551
Novartis Investigative Site Recruiting
Wiesbaden, Germany, 65191
Novartis Investigative Site Recruiting
Wolfsburg, Germany, 38440
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01514448     History of Changes
Other Study ID Numbers: CRAD001LDE43, 2011-003416-23
Study First Received: January 17, 2012
Last Updated: February 25, 2013
Health Authority: United States: Food and Drug Administration
Germany: Bundesamt für Arzneimittel und Medizinprodukte (BfArM)

Keywords provided by Novartis:
Kidney cancer
mRCC
metastic renal cell carcinoma
 everolimus
sunitinib
pazopanib

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Everolimus
Sirolimus
Sunitinib
 Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on May 16, 2013