Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Amino Acids

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Glutamine

CB-839 is administered as oral tablets twice daily (BID) in combination with standard daily (QD) everolimus in 28 day cycles.

Placebo is administered as oral tablets BID in combination with standard QD everolimus in 28 day cycles.

Placebo

CB-839

everolimus

Sam Whiting

The primary objective of this study is to compare the progression-free survival (PFS) of participants treated with telaglenastat and everolimus versus placebo and everolimus for advanced or metastatic clear cell renal cell carcinoma (ccRCC) previously treated with the following:

* At least 2 lines of therapy, including at least 1 vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI)
* Radiographic progression of metastatic RCC must have occurred (per investigator assessment) on or after the most recent systemic therapy and within 6 months prior to cycle 1 day 1

This is a double blinded placebo-controlled study where participants will be randomized 2:1 to either CB-839 plus everolimus (CBE) or placebo plus everolimus (PboE)

CB-839 With Everolimus vs. Placebo With Everolimus in Participants With Renal Cell Carcinoma (RCC)

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)

PFS was defined as the time from randomization to the date of documented disease progression (assessed by Investigator per Response Evaluation Criteria in Solid Tumors \[RECIST\] v1.1) within 2 scheduled scan intervals following previous evaluable radiologic tumor assessment or death for any cause, whichever occurred first. Participants with no documentation of disease progression or death on-study were censored at the date of last available tumor assessment.

Progressive Disease (PD) per RECIST 1.1: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm.

Overall survival is defined as the time from randomization to the date of death from any cause. Participants with no documentation of death on-study were censored at the date at which they were last known to be alive.

Calithera Biosciences, Inc

Placebo oral tablets BID in combination with standard QD everolimus in 28 day cycles.

Placebo + Everolimus

CB-839 oral tablets BID in combination with standard QD everolimus in 28 day cycles.

CB-839 + Everolimus

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Study Director

Stratified analysis. Stratification factors were Memorial Sloan Kettering Cancer Center (MSKCC) Prognostic Risk (favorable versus intermediate/poor risk) and number of prior therapies with a tyrosine kinase inhibitor (TKI; 1 versus \> 1). Due to stratification cells having \< 10 events, TKI stratification factor was removed for analysis.

Intent to Treat Population: all randomized participants.

Progression Free Survival (PFS)

Stratified analysis: Stratification factors are MSKCC Prognostic Risk (favorable vs intermediate/poor risk) and number of prior therapies with a TKI (1 vs \> 1). Due to stratification cells having \< 10 events, TKI stratification factor was removed for analysis.

ITT Population: all randomized participants.

Overall Survival (OS)

Placebo oral tablets twice daily (BID) in combination with standard once daily (QD) everolimus in 28 day cycles.

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Digestive System Diseases

Nervous System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Wounds and Injuries

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Breast Neoplasms

Triple Negative Breast Neoplasms

Gastrointestinal Stromal Tumors

Hematoma, Subdural

Mesothelioma

Mesothelioma, Malignant

Breast Diseases

Skin Diseases

Adenoma

Neoplasms, Mesothelial

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Malignant Mesothelioma

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

CB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity

CB-839 administered as oral capsules twice daily (BID) in combination with standard dose paclitaxel in 28-day cycles until disease progression or unacceptable toxicity

CB-839 administered as oral capsules twice daily (BID) in combination with standard dose everolimus in 28-day cycles until disease progression or unacceptable toxicity

CB-839 administered as oral capsules twice daily (BID) in combination with standard dose erlotnib in 28-day cycles until disease progression or unacceptable toxicity

CB-839 administered as oral capsules twice daily (BID) in combination with standard dose docetaxel in 21-day cycles until disease progression or unacceptable toxicity

CB-839 administered as oral capsules twice daily (BID) in combination with standard dose cabozantinib in 28-day cycles until disease progression or unacceptable toxicity

CB-839 in combination with standard dose paclitaxel

Pac-CB

CB-839 in combination with standard dose everolimus

CB-839 in combination with standard dose erlotnib

CB-Erl

CB-839 in combination with standard dose docetaxel

CB-839 in combination with standard dose cabozantinib

CB-Cabo

Samuel Whiting, MD, PhD

Many tumor cells, in contrast to normal cells, have been shown to require the amino acid glutamine to produce energy for growth and survival. To exploit the dependence of tumors on glutamine, CB-839, a potent and selective inhibitor of the first enzyme in glutamine utilization, glutaminase, will be tested in this Phase 1 study in patients with solid tumors.

This study is an open-label Phase 1 evaluation of CB-839 in patients with advanced solid tumors. The study will be conducted in 2 parts. Part 1 is a dose escalation study enrolling patients with locally-advanced, metastatic and/or refractory solid tumors to receive CB-839 capsules orally twice or three times daily.

In Part 2, patients with each of the following diseases will be enrolled: A) Triple-Negative Breast Cancer, B) Non-Small Cell Lung Cancer (adenocarcinoma), C) Renal Cell Cancer, D) Mesothelioma, E) Fumarate hydratase (FH)-deficient tumors, F) Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GIST), G) SDH-deficient non-GIST tumors, H) tumors harboring mutations in isocitrate dehydrogenase-1 (IDH1) or IDH2, and I) cMyc mutation tumors.

As an extension of Parts 1 \& 2, patients will be treated with CB-839 in combination with standard chemotherapy. Combination groups include: Pac-CB, CBE, CB-Erl, CBD, and CB-Cabo. Pac-CB: patients with locally-advanced or metastatic TNBC will be treated with paclitaxel and CB-839. CBE: patients with advanced clear cell RCC or papillary RCC will be treated with everolimus in combination with CB-839. CB-Erl: patients with advanced NSCLC lacking the T790M EGFR mutation will be treated with erlotinib and CB-839. CBD: patients with NSCLC harboring KRAS mutation will be treated with docetaxel and CB-839. CB-Cabo: patients with histologically confirmed diagnosis of locally-advanced, inoperable or metastatic RCC treated with cabozantinib in combination with CB-839.

All patients will be assessed for safety, pharmacokinetics (plasma concentration of drug), pharmacodynamics (inhibition of glutaminase), biomarkers (biochemical markers that may predict responsiveness in later studies), and tumor response.

Study of the Glutaminase Inhibitor CB-839 in Solid Tumors

Ph1 Study of the Safety, PK, and PDn of Escalating Oral Doses of the Glutaminase Inhibitor CB-839, as a Single Agent and in Combination With Standard Chemotherapy in Patients With Advanced and/or Treatment-Refractory Solid Tumors

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CB-839 With Everolimus vs. Placebo With Everolimus in Participants With Renal Cell Carcinoma (RCC)	NCT03163667	Clear Cell Rena...	Placebo CB-839 everolimus	18 Years -	Calithera Biosciences, Inc
CB-839 With Everolimus vs. Placebo With Everolimus in Participants With Renal Cell Carcinoma (RCC)	NCT03163667	Clear Cell Rena...	Placebo CB-839 everolimus	18 Years -	Calithera Biosciences, Inc
Study of the Glutaminase Inhibitor CB-839 in Solid Tumors	NCT02071862	Solid Tumors Triple-Negative... Non Small Cell ... Renal Cell Carc... Mesothelioma Fumarate Hydrat... Succinate Dehyd... Succinate Dehyd... Tumors Harborin... Tumors Harborin...	CB-839 Pac-CB CBE CB-Erl CBD CB-Cabo	18 Years -	Calithera Biosciences, Inc

Spots Global Cancer Trial Database for cbe

Every month we try and update this database with for cbe cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cbe

Every month we try and update this database with for cbe cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cbe cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.