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

NCT02071641 | Terminated Phase 2

• 1 other identifier: 2012/259
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  To investigate the proportion of patients with metastic Renal Cell Carcinoma retreated with sunitinib that is progression-free at 3 months.

  After 3 months of treatment

Secondary Outcomes (6)

• Clinical benefit rate

  progression free at 3 months

• Effects of sunitinib rechallenge on LAMP1/2 proteins

  Blood samples will be collected at baseline, t=4 wk, t=6 wk, t=12 wk and at the end of study treatment (disease progression and/or death)

• The immunological effects of sunitinib rechallenge

  Blood samples will be collected at baseline, t=4 wk, t=6 wk, t=12 wk and at the end of study treatment (disease progression and/or death).

• Mass spectrometry-based identification of phosphorylated proteins in tumor tissue during treatment

  Blood samples will be collected at baseline, t=4 wk, t=6 wk, t=12 wk and at the end of study treatment (disease progression and/or death).

• Concentrations of sunitinib

  Blood samples will be collected at baseline, t=4 wk, t=6 wk, t=12 wk and at the end of study treatment (disease progression and/or death).

Study Arms (1)

Sunitinib

EXPERIMENTAL

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

Drug: Sunitinib

Interventions

Sunitinib DRUG

Sunitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients with radiological (and/or clinical) confirmed progressive disease according to RECIST 1.1 criteria.
• Measurable or evaluable disease as defined by RECIST 1.1.
• WHO performance status 0-2.
• Life expectancy of at least 12 weeks.
• Age 18 years or older.
• Able to receive oral medication.
• Able to provide written informed consent.
• Adequate hematologic function: Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, Hb ≥ 6.0 mmol/L.
• Patients with brain metastases are eligible if they have been stable for at least two months post-radiation therapy or surgery.
• No other current malignant disease, except for basal cell carcinoma of the skin.
• 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).
• Renal function: estimated glomerular filtration rate ≥ 40 ml/min.
• Patients with reproductive potential must use effective contraception. Female patients must have a negative pregnancy test.
• Patients treated with any VEGF targeted TKI (sorafenib, pazopanib, axitinib, dovitinib) as second-line treatment after progression on first-line sunitinib treatment.
• 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.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

VU Medical Center

Amsterdam, 1081 HV, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Sunitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 27, 2013
• First Posted: February 26, 2014
• Study Start: October 1, 2012
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: April 7, 2017

Record last verified: 2017-04

Locations

NL (1)