ENTRATA: CB-839 With Everolimus vs. Placebo With Everolimus in Patients With RCC (ENTRATA)

• ClinicalTrials.gov Identifier: NCT03163667
• Recruitment Status: Active, not recruiting
• First Posted: May 23, 2017
• Last Update Posted: February 15, 2019
• Sponsor: Calithera Biosciences, Inc
• Information provided by (Responsible Party): Calithera Biosciences, Inc

Study Description

Brief Summary:

Phase 2 Study Comparing CB-839 in Combination with Everolimus (CBE) vs. Placebo with Everolimus (PboE) in Patients with Advanced or Metastatic RCC

Condition or disease	Intervention/treatment	Phase
Clear Cell Renal Cell Carcinoma	Drug: CB-839 plus everolimus; Drug: Placebo plus everolimus	Phase 2

Detailed Description:

A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study Comparing CB-839 in Combination with Everolimus (CBE) vs. Placebo with Everolimus (PboE) in Patients with Advanced or Metastatic Renal Cell Carcinoma (RCC)

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a double blinded placebo-controlled study where patients will be randomized 2:1 to either CB-839 plus everolimus (CBE) or placebo plus everolimus (PboE)
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double blinded, placebo-controlled
• Primary Purpose: Treatment
• Official Title: ENTRATA- A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study Comparing CB-839 in Combination With Everolimus (CBE) vs. Placebo With Everolimus (PboE) in Patients With Advanced or Metastatic Renal Cell Carcinoma (RCC)
• Actual Study Start Date: July 1, 2017
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: December 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: CB-839 plus everolimus; CBE: CB-839 is administered twice daily in combination with standard doses of everolimus	Drug: CB-839 plus everolimus; CB-839 is administered as oral tablets twice daily (BID) in combination with standard daily (QD) everolimus in 28 day cycles.; Other Name: Afinitor
Placebo Comparator: Placebo plus everolimus; PboE: Placebo is administered twice daily in combination with standard doses of everolimus	Drug: Placebo plus everolimus; Placebo is administered as oral tablets twice daily (BID) in combination with standard daily (QD) everolimus in 28 day cycles.; Other Name: Afinitor

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: 30 months ]
   Assessed by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Secondary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: 42 months ]
   Assessed by time from randomization to death by any cause

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:

• Karnofsky Performance Score (KPS) ≥ 70%
• Estimated Life Expectancy of at least 3 mo
• Documented histological or cytological diagnosis of renal cell carcinoma with a clear-cell component.
• Measurable Disease per RECIST 1.1 as determined by the Investigator

• Must have received at least two prior lines of systemic therapy, including at least one VEGFR-targeting TKI (e.g., sunitinib, sorafenib, pazopanib, cabozantinib)

  a) Radiographic progression of mRCC must have occurred (per investigator assessment) on or after the most recent systemic therapy and within 6 mo prior to C1D1.

• Prior treatment with other anti-cancer therapies including cytokines, monoclonal antibodies, immunotherapies, and cytotoxic chemotherapy is allowed

Exclusion Criteria:

• Prior treatment with mTOR inhibitors (everolimus or temsirolimus) or CB-839

• Receipt of any anticancer therapy within the following windows before randomization:

  • TKI therapy within 2 weeks or 5 half-lives, whichever is longer
  • Any type of anti-cancer antibody within 4 weeks
  • Cytotoxic chemotherapy within 4 weeks
  • Investigational therapy within 4 weeks or 5 half-lives, whichever is longer
  • Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before randomization. Patients with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Unable to receive medications PO or any condition that may prevent adequate absorption of oral study medication
• Major surgery within 28 days prior to randomization
• Patients with active and/or untreated central nervous system (CNS) cancer are not eligible. Patients with treated brain metastasis must have 1) documented radiographic stability of at least 4 weeks duration demonstrated on baseline contrast-enhanced CNS imaging (eg contrast-enhanced MRI of the brain) prior to randomization and 2) must be symptomatically stable and off steroids for at least 2 weeks before randomization.
• Requirement for continued proton pump inhibitor after randomization
• Chronic treatment with corticosteroids or other immunosuppressive agents except (i) inhaled or topical steroids or replacement dose corticosteroids equivalent to ≤ 10 mg prednisone and (ii) patients receiving physiological doses of hydrocortisone for adrenal insufficiency

Contacts and Locations

  Show 38 Study Locations

Sponsors and Collaborators

Calithera Biosciences, Inc

Investigators

• Study Director: Sam Whiting; Calithera Biosciences

More Information

Additional Information:

Calithera Biosciences Company website 

• Responsible Party: Calithera Biosciences, Inc
• ClinicalTrials.gov Identifier: NCT03163667 History of Changes
• Other Study ID Numbers: CX-839-005
• First Posted: May 23, 2017
• Last Update Posted: February 15, 2019
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Calithera Biosciences, Inc:

advanced, metastatic RCC; RCC; CB-839; Everolimus; CBE; Glutaminase Inhibitor; Glutaminase; Tumor Metabolism; Glutamine

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; Sirolimus; Everolimus; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antifungal Agents