Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

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

Bevacizumab

Everolimus

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Study treatment, consisting of bevacizumab + everolimus, was administered as 28-day cycles

Bevacizumab 10 mg/kg administered by IV infusion every 14 days (dose suspension permitted, dose reduction not permitted)

Everolimus 10 mg daily was administered orally (dose reduction to 5 mg daily and then 5 mg every other day, was permitted as needed for toxicity or tolerability)

Dr. Sandy Srinivas

To determine the safety and efficacy of the combination of bevacizumab and everolimus (RAD001) for the treatment of metastatic renal cell cancer

Treatment of Refractory Metastatic Renal Cell Carcinoma With Bevacizumab and RAD001 (Everolimus)

Progression-free survival (PFS) per RECIST criteria

Number of subjects with objective response (OR)

Number of subjects whose treatment was discontinued due to toxicity

Number of subjects whose treatment was discontinued due to disease progression

Genentech, Inc.

Novartis

Sandy Srinivas

Associate Professor

Bevacizumab + RAD001 (Everolimus)

Study treatment, consisting of bevacizumab + everolimus, was administered as 28-day cycles

Bevacizumab 10 mg/kg administered by IV infusion every 14 days (dose suspension permitted, dose reduction not permitted)

Everolimus 10 mg daily was administered orally (dose reduction to 5 mg daily and then 5 mg every other day, was permitted as needed for toxicity or tolerability)

Everolimus

Bevacizumab

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Associate Professor of Medicine (Oncology)

Objective Response (OR)

Objective Response (OR) Duration

Time-to-Treatment Failure (TTF)

Overall Survival (OS)

Number of Subjects With Drug-related SAEs

Total Number of Drug-related SAEs

Treatment Discontinuation Due to Toxicity

Treatment Discontinuation Due to Disease Progression

Progression-free Survival (PFS)

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Prostatic Neoplasms

Breast Neoplasms

Pancreatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Melanoma

Thyroid Neoplasms

Thyroid Diseases

Skin Neoplasms

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Herbal and Botanical

Cola

Subjects with solid tumors who satisfy the eligibility criteria will receive two, 21-day cycles of CALAA-01. A cycle will consist of four (4) 30-minute intravenous infusions administered on days 1, 3, 8, and 10 followed by 11 days of rest. If safe, a second 21-day cycle will be administered consisting of infusions on days 22, 24, 29 and 31 followed by 11 days of rest.

CALAA-01

Antoni Ribas, M.D.

Anthony W Tolcher, M.D.

Yun Yen, M.D., Ph.D.

Rationale: CALAA-01 is a targeted therapeutic designed to inhibit tumor growth and/or reduce tumor size. The active ingredient in CALAA-01 is a small interfering RNA (siRNA). This siRNA inhibits tumor growth via RNA interference to reduce expression of the M2 subunit of ribonucleotide reductase (R2). The CALAA-01 siRNA is protected from nuclease degradation within a stabilized nanoparticle targeted to tumor cells.

PURPOSE: This phase I trial will:

* Determine the safety, toxicity, and the maximum tolerated dose (MTD) of CALAA-01 when administered intravenously to patients with relapsed or refractory cancer.
* Characterize the pharmacokinetics (PK) of CALAA-01 after intravenous administration.
* Provide preliminary evidence of efficacy of intravenous CALAA-01 by evaluating tumor response.
* Recommend a dose of intravenous CALAA-01 for future clinical studies.
* Evaluate immune response, by measuring antibody and cytokine levels, and the effect of intravenous CALAA-01 on complement.

CALAA-01 is a targeted nanocomplex that contains anti-R2 siRNA. The complete nanocomplex formulation consists of four components:

1. a duplex of synthetic, non-chemically-modified siRNA (C05C)
2. a cyclodextrin-containing polymer (CAL101),
3. a stabilizing agent (AD-PEG), and
4. a targeting agent (AD-PEG-Tf) that contains the human transferrin protein (Tf). The cationic polymer interacts electrostatically with anionic siRNA to assemble into nanocomplexes below approximately 100 nm in diameter that protect the siRNA from nuclease degradation in serum. The siRNA-containing nanocomplexes are targeted to cells that over express the transferrin receptor (TfR). Upon reaching a target cell, transferrin binds to TfRs on the cell surface and the siRNA-containing nanocomplex enters the cell by endocytosis. Inside the cell, chemistry built into the polymer achieves unpackaging of the siRNA from the nanocomplex, permitting it to function via RNA interference.

Safety Study of CALAA-01 to Treat Solid Tumor Cancers

A Phase I, Dose-Escalating Study of the Safety of Intravenous CALAA-01 in Adults With Solid Tumors Refractory to Standard-of-Care Therapies

Calando Pharmaceuticals

Fluorodeoxyglucose F18

Sunitinib

Radiopharmaceuticals

FDG PET CT F-18 Fluoro-deoxi-glucose: 15 mCi iv Gadolinium-DTPA: 0.1 mmol/kg Sunitinib: 50 mg/day po

nuclear medicine imaging technique which produces a three-dimensional image or picture of functional processes in the body

FDG PET CT

DCE MRI will be acquired using rapid intravenous bolus of gadolinium-DTPA (0.1 mmol/kg).

DCE MRI

F-18 Fluoro-deoxi-glucose

Gadolinium-DTPA

Dr Andrew Quon

To learn whether Flourine-18 Fluoro-deoxi-glucose positron emission tomography / computed tomography (F-18 FDG PET/CT) and dynamic contrast enhanced magnetic resonance imaging (DCE MRI) are better predictors of response to therapy than the current standard of care (CT or MRI).

This is a single arm prospective trial in patients with newly-diagnosed advanced renal cell cancer (RCC) who were scheduled for sunitinib therapy and utilized an extensive panel of quantitative metrics on baseline and interim FDG PET/CT to evaluate the predictive utility of each of these measurements.

The objectives were to evaluate the FDG PET/CT measurement parameters for prediction of prognosis after sunitinib therapy in patients with RCC using histopathologic (post-therapy nephrectomy) or clinical follow-up for validation.

Evaluating Sunitinib Therapy in Renal Cell Carcinoma Using F-18 FDG PET/CT and DCE MRI

De-identified (anonymized) patient data is routinely provided upon request. Protecting patient privacy and confidentiality is the utmost consideration when sharing individual patient data. In all cases of data sharing, patient data is always anonymized to protect privacy. All potential identifiers (name, hospital ID, address,etc) are removed.

The maximum standardized uptake value (SUVmax) is a measurement of tumor metabolism as determined by the PET scan before and after 12-weeks of sunitinib therapy. Decreased SUVmax correlates to a reduction of tumor metabolism. Increased SUVmax correlates to an increase in tumor metabolism.

Reduction or increased SUVmax will be determined as the change from baseline in uptake of F18 FDG.

Results were based on the European Organization for Research and Treatment of Cancer (EORTC) for predicting progression free survival. EORTC criteria is a ± 25% change of SUVmax for assessment of progressive disease, stable disease and partial response.

Histopathologic findings were correlated to the pre-treatment 18F-fluorodeoxyglucose positron emission tomography (F-18 FDG PET/CT) scan. Outcome is reported as the number of participants for whom both histopathology and F-18 FDG PET/CT indicated that active cancers was present.

A comprehensive metabolic panel is a blood test that measures sugar (glucose) level, electrolyte and fluid balance, kidney function, and liver function. It was performed prior to the administration of gadolinium contrast. For patients with normal renal function, approximately 90% of gadolinium contrast is excreted through the urinary system. These patients have known renal cell carcinoma, so it was important to perform a metabolic function panel prior to gadolinium injection, specifically to determine kidney function. Reported as the number of patients for whom the initial comprehensive metabolic panel was within institutional standards.

Adverse events were monitored for on F-18 FDG PET/CT and DCE MRI imaging days: baseline (n=17); interim (n=12); and post-sunitinib therapy (n=17). Reported as the overall number of adverse events experienced.

The degree of tumor necrosis was measured using values obtained from dynamic contrast enhanced magnetic resonance imaging (DCE MRI) pre- and post-sunitinib therapy. Gadolinium contrast material given intravenously during the DCE MRI scan is used to improve visualization of blood vessels, tumors, and/or organs.

Tumor size was measured based on computed tomography (CT) pre- and post-sunitinib therapy. CT was performed immediately prior to the PET scan and is used to determine both the PET scan imaging area and PET image attenuation correction (AC). F-18 FDG PET provides the metabolic and physiologic data while CT provides the anatomical data.

Tumor size was measured using values obtained from DCE MRI pre- and post-sunitinib therapy. Gadolinium contrast material given intravenously during the DCE MRI scan is used to improve visualization of blood vessels, tumors, and/or organs.

Area under the curve (AUC) was measured using receiver operating characteristic (ROC) curve analysis. ROC curve analysis measures sensitivity (true-positives, correctly diagnosed positive pathologies) against specificity (true-negatives, correctly diagnosed negative pathologies or free of disease) of the DCE MRI scan. An area of 1.0 under the curve would equal a perfect test (with 100% sensitivity; 100% specificity) while an area of 0.5 would equal a useless test (50% sensitivity; 50% specificity).

Initial tumor size was measured using values obtained from computed tomography (CT) pre-sunitinib therapy. CT is performed immediately prior to the PET scan and is used to determine both the PET scan imaging area and PET image attenuation correction (AC). F-18 FDG PET provides the metabolic and physiologic data while CT provides the anatomical data.

National Comprehensive Cancer Network

Stanford University

Associate Professor of Radiology (Nuclear Medicine

No adverse events were noted, and none are reported.

15 mCi iv F-18 FDG PET/CT scan and DCE MRI using Gadolinium-DTPA: 0.1 mmol/kg iv followed by Sunitinib therapy at 50 mg/day.

F-18 FDG PET/CT and DCE MRI

FDG PET CT F-18 Fluoro-deoxi-glucose: 15 mCi iv Gadolinium-DTPA: 0.1 mmol/kg Sunitinib: 50 mg/day po

FDG PET CT: nuclear medicine imaging technique which produces a three-dimensional image or picture of functional processes in the body

DCE MRI: DCE MRI will be acquired using rapid intravenous bolus of gadolinium-DTPA (0.1 mmol/kg).

F-18 Fluoro-deoxi-glucose: 15 mCi iv

Gadolinium-DTPA: 0.1 mmol/kg iv

Sunitinib: 50 mg/day po

Age, Categorical

The utility of the MRI- and CT-scans was significantly limited by low image quality.

Andrew Quon, M.D. Professor Division of Nuclear Medicine

Baseline SUVmax

Mean SUVmax, progression-free survival

SUVmax, progression/relapse

All patients underwent baseline F-18 FDG PET scan. Mean SUVmax at baseline is reported (row 1). 6 participants achieved progression-free survival after post-sunitinib therapy, and their SUVmax values were averaged (row 2). 11 participants had progression or recurrence/relapse of disease and their SUVmax values were averaged (row 3).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Treatment of Refractory Metastatic Renal Cell Carcinoma With Bevacizumab and RAD001 (Everolimus)	NCT00651482	Kidney Neoplasm... Kidney (Renal C...	Everolimus Bevacizumab	18 Years -	Stanford University
Safety Study of CALAA-01 to Treat Solid Tumor Cancers	NCT00689065	Cancer Solid Tumor	CALAA-01	18 Years -	Calando Pharmaceuticals
Evaluating Sunitinib Therapy in Renal Cell Carcinoma Using F-18 FDG PET/CT and DCE MRI	NCT00537056	Kidney Neoplasm... Carcinoma, Rena... Kidney (Renal C...	FDG PET CT DCE MRI F-18 Fluoro-deo... Gadolinium-DTPA Sunitinib	18 Years -	Stanford University
B-Receptor Signaling in Cardiomyopathy	NCT01135849	Carcinomas Amyloidosis Anal Cancer Anemia Cholangiocarcin... Transitional Ce... Bone Marrow Tra... Bone Cancer Cancer of Brain... Breast Cancer Carcinoma of th... Endocrine Cance... Esophageal Canc... Eye Cancer Gall Bladder Ca... Gastric (Stomac... Gastrooesophage... Gastrointestina... Gynecologic Can... Head and Neck C... Hepatobiliary N... Kidney (Renal C... Leukemia Lung Cancer Hodgkin Disease Lymphoma, Non-H... Mesothelioma Multiple Myelom... Myelodysplastic... Neuroendocrine ... Myeloproliferat... Pancreatic Canc... Prostate Cancer Skin Cancer Soft Tissue Sar... Testicular Canc... Thymus Cancer Thyroid Cancer		- 40 Years	Stanford University
B-Receptor Signaling in Cardiomyopathy	NCT01135849	Carcinomas Amyloidosis Anal Cancer Anemia Cholangiocarcin... Transitional Ce... Bone Marrow Tra... Bone Cancer Cancer of Brain... Breast Cancer Carcinoma of th... Endocrine Cance... Esophageal Canc... Eye Cancer Gall Bladder Ca... Gastric (Stomac... Gastrooesophage... Gastrointestina... Gynecologic Can... Head and Neck C... Hepatobiliary N... Kidney (Renal C... Leukemia Lung Cancer Hodgkin Disease Lymphoma, Non-H... Mesothelioma Multiple Myelom... Myelodysplastic... Neuroendocrine ... Myeloproliferat... Pancreatic Canc... Prostate Cancer Skin Cancer Soft Tissue Sar... Testicular Canc... Thymus Cancer Thyroid Cancer		- 40 Years	Stanford University

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