Phase II Study of Sunitinib Rechallenge in Patients With Metastatic Renal Cell Carcinoma

NCT ID: NCT02071641

Last Updated: 2017-04-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2016-09-30

Brief Summary

Targeted therapies are associated with (acquired) resistance after a median of 5-11 months of treatment, resulting in disease progression, while almost no tumors are intrinsically resistant in the first line setting. The investigators recently published that tumor cell resistance to sunitinib may be directly related to lysosomal sequestration of sunitinib. This resistance mechanism was shown to be transient, since a drug-free culture period could normalize the lysosomal storage capacity for sunitinib and resulted in recovery of drug sensitivity.

In two reports it has been suggested that patients with metastatic Renal Cell Carcinoma who responded to sunitinib in the first-line setting may benefit from rechallenge with sunitinib after failure of second-line treatment. However, these data are retrospective. A prospective trial to investigate a rechallenge with sunitinib is needed to determine whether this strategy is of benefit for patients with mRCC with prior clinical benefit to sunitinib but who stopped treatment because of overt clinical resistance.

Conditions

Metastatic Renal Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sunitinib

Patients will be treated in repeated 6-week cycles with 50 mg sunitinib orally daily for 4 weeks followed by 2 weeks off.

Group Type: EXPERIMENTAL

Sunitinib

Intervention Type: DRUG

Interventions

Sunitinib

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients with histologically or cytologically confirmed clear-cell mRCC.

2. Patients who progressed on first-line treatment with sunitinib and who had clinical benefit defined as a response (according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria) or SD for more than 6 months on this treatment.

Exclusion Criteria

4. Patients with radiological (and/or clinical) confirmed progressive disease according to RECIST 1.1 criteria.

5. Measurable or evaluable disease as defined by RECIST 1.1.

6. WHO performance status 0-2.

7. Life expectancy of at least 12 weeks.

8. Age 18 years or older.

9. Able to receive oral medication.

10. Able to provide written informed consent.

11. Adequate hematologic function: Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, Hb ≥ 6.0 mmol/L.

12. Patients with brain metastases are eligible if they have been stable for at least two months post-radiation therapy or surgery.

13. No other current malignant disease, except for basal cell carcinoma of the skin.

14. Adequate hepatic function: serum bilirubin ≤ 1.5 x Upper Limit of Normal (ULN), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 x ULN (or ≤ 5 times ULN if liver metastases are present).

15. Renal function: estimated glomerular filtration rate ≥ 40 ml/min.

16. Patients with reproductive potential must use effective contraception. Female patients must have a negative pregnancy test.

1. Patients treated with any VEGF targeted TKI (sorafenib, pazopanib, axitinib, dovitinib) as second-line treatment after progression on first-line sunitinib treatment.

2. Uncontrolled hypertension. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen. Blood pressure must be stable on at least 2 separate measurements on at least 2 separate days.

3. Active infection or serious intercurrent illness.

4. Presence of unstable angina, recent myocardial infarction (within the previous 3 months).

5. Macroscopic hematuria.

6. Presence of any significant central nervous system or psychiatric disorder(s) that would hamper the patient's compliance.

7. Any other major illness that, in the investigator's judgment, substantially increases the risk associated with the subject's participation in the study.-

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: lead

Responsible Party

H.M.W. Verheul

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

VU Medical Center

Amsterdam, , Netherlands

Countries

Netherlands

Other Identifiers

2012/259

Identifier Type: -

Identifier Source: org_study_id