Vandetanib in Combination With Metformin in People With HLRCC or SDH-Associated Kidney Cancer or Sporadic Papillary Renal Cell Carcinoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02495103|
Recruitment Status : Recruiting
First Posted : July 13, 2015
Last Update Posted : March 22, 2018
- There are no established treatments for people with certain advanced kidney cancers. These tumors often don t respond well to currently available treatments. Researchers believe that two drugs that treat other diseases metformin and vandetanib could help people with advanced kidney cancer.
- To test the combination of metformin and vandetanib in people with advanced kidney cancer. Phase I of the study will determine a safe dose for the drugs. Phase II will test this dose in people with certain kidney cancers.
- For Phase I, people 18 and over with advanced kidney cancer
- For Phase II, people 18 and over with advanced hereditary leiomyomatosis and renal cell cancer (HLRCC), succinate dehydrogenase renal cell carcinoma (SDH-RCC), or advanced papillary renal cell carcinoma not related to a hereditary syndrome
- The study will last many months.
- Participants will be screened with medical history and physical exam.
- Participants will take the study drugs by mouth every day.
- Participants will measure and record their blood pressure every day.
- Participants will have many tests:
- Blood and urine tests
- MRI, CT, PET scan, and other imaging tests: they will lie in machines that take pictures of their body.
- ECG: soft electrodes will be stuck to the skin. A machine will record the heart s signals.
- Bone scan
- Some participants may have a gynecology evaluation or photos of skin tumors taken.
- Participants will have an optional tumor biopsy.
- After they stop taking the drugs, participants may have medical history, physical exam, and blood tests. They will be contacted once a year by phone to find out how they are doing.
|Condition or disease||Intervention/treatment||Phase|
|Renal Cell Carcinoma Hereditary Leiomyomatosis and Renal Cell Cancer Papillary Renal Cell Carcinoma, Sporadic||Drug: Vandetanib Drug: Metformin Drug: Vandetanib/Metformin||Phase 1 Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||73 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Trial of Vandetanib in Combination With Metformin in Subjects With HLRCC or SDH-Associated Kidney Cancer or Sporadic Papillary Renal Cell Carcinoma|
|Study Start Date :||July 8, 2015|
|Estimated Primary Completion Date :||May 1, 2021|
|Estimated Study Completion Date :||May 1, 2022|
Phase II Component
Phase II: Vandetanib and metformin PO daily at determined MTD.
Phase I Component
PHASE I: Vandetanib PO daily at 300mg in combination with escalating doses of metformin.Drug: Metformin
Phase I: Metformin starting dose 250mg PO daily in combination with Vandetanib
- Phase 1 Component: To establish the safety and maximum tolerated dose (MTD) of vandetanib and metformin when used in combination in patients with metastatic RCC. [ Time Frame: 42 days after the last patient starts therapy. ]List of adverse events frequency and MTD
- Phase 2 Component: To determine the overall response rate (RECIST 1.1) following treatment with the combination of vandetanib and metformin in patients with 1) advanced RCC associated with HLRCC or SDH, and 2) advanced sporadic/non-HLRCC papilla... [ Time Frame: 3 years after the last patient finishes therapy. ]Percentage of patients who have a response to therapy.
- Phase 1 Component: Evaluate the clinical activity of the combination of vandetanib and metformin [ Time Frame: 2-3 years ]
- Phase 1 Component: Evaluate modulation of the biochemical and metabolic phenotype following therapy using paired pre- and on-treatment tumor biopsies (when available) [ Time Frame: 2-3 years ]
- Phase 1 Component: Identify drug interaction between metformin and vandetanib at clinically-relevant doses [ Time Frame: 2-3 years ]
- Phase 2 Component: Assess duration of response, progression-free survival and overall survival with this combination [ Time Frame: 2-3 years ]
- Phase 2 Component: Investigate the effect of vandetanib/metformin on potential biomarkers of angiogenesis in plasma such as VEGF and soluble VEGFR2 [ Time Frame: 2-3 years ]
- Phase 2 Component: Evaluate modulation of the biochemical and metabolic phenotype following therapy using paired pre- and on-treatment tumor biopsies (when available) [ Time Frame: 2-3 years ]
- Phase 2 Component: Evaluate the prevalence of somatic fumarate hydratase (FH) and succinate dehydrogenase (SDH)mutations/inactivation as well as activation of/mutations in theNRF2/KEAP1/CUL3 pathway in patients with sporadic papillary RCC and... [ Time Frame: 2-3 years ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02495103
|Contact: Martha Ninos, R.N.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Ramaprasad Srinivasan, M.D.||National Cancer Institute (NCI)|