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Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors

Phase 4
18 Years
Open (Enrolling)
Renal Cell Carcinoma, Gastrointestinal Stromal Tumor

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Trial Information

Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors

Until now, in trials it is common to stop therapy when progressive disease occurs; RECIST
criteria are used, in which progressive disease is defined as >20% increase of the sum of
the longest diameter of the lesions, or occurence of new lesions. However, angiogenesis
inhibitors have a rather cytostatic than cytotoxic effect compared to chemotherapeutics, as
a result of which less frequently reduction of tumor volume is being seen.

Often in the centre of the lesion necrosis is shown. Sometimes accompanied with edema; so
even tumor volume increase can be the result without real progression being the case.
Recently, in our clinic, we found a number of patients, treated with oral angiogenesis
inhibitors, a remarkable quickening of progressive disease and complaints after stopping
this treatment. Reintroduction of the same or another type of angiogenesis inhibitor
subsequently lead to a new stabilization. The causality of this phenomenon is unknown.
Perhaps that the inhibitory effect of the angiogenesis is not fully exhausted at the moment
that progressive disease on CT is observed. An alternative explanation is contra reaction of
longterm angiogenetic inhibition through upregulation of proangiogenic factors with
subsequent vascular expansion and edema. This study means to gain more insight information
about the optimal treatment policy when progressive disease is found in patients treated
with oral angiogenesis inhibitors. Because of the increase of patients that is being treated
with these products, both in trials as in daily clinical practice, this is important to

Inclusion Criteria:

- metastatic or advanced solid cancer that is treated with an oral angiogenesis
inhibitor, with clinical indication to stop this therapy based on progressive disease
as defined by the RECIST criteria on the CT scan. It needs a minimum of 1 previous
evaluation of stable disease and the patient must have been treated with angiogenesis
inhibitors for at least 12 weeks.

- age ≥18 years

- given informed consent

Exclusion Criteria:

- pregnant or lactating

- metastatic sites solely in bone or liver

- contraindication for CT or Avastin scan (claustrophobia, severe renal function
disorder, allergy for contrast fluids, allergy for Avastin)

- insufficient condition to continue treatment with angiogenesis inhibitors.

- contraindication for dynamic contrast MRI (deteriorated renal functions with
clearance <60ml/min, metal in body, claustrophobia, pacemaker, defibrillator)

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Signs of progressive disease on CT-scan, DCE-MRI or Avastin scan

Outcome Time Frame:

4 weeks

Safety Issue:


Principal Investigator

C.M.L. van Herpen, MD, Phd

Investigator Role:

Principal Investigator

Investigator Affiliation:

UMCN st Radboud


Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Study ID:




Start Date:

October 2008

Completion Date:

April 2012

Related Keywords:

  • Renal Cell Carcinoma
  • Gastrointestinal Stromal Tumor
  • angiogenesis
  • inhibitor
  • duration of therapy
  • GIST
  • Carcinoma
  • Carcinoma, Renal Cell
  • Gastrointestinal Stromal Tumors