A RANDOMIZED PHASE II DOUBLE-BLIND TRIAL OF SUNITINIB VERSUS PLACEBO IN COMBINATION WITH LANREOTIDE IN PATIENTS WITH PROGRESSIVE ADVANCED/METASTATIC MIDGUT CARCINOID TUMORS
Overview
- Phase
- Phase 2
- Intervention
- Lanreotide
- Conditions
- Carcinoid Tumors
- Sponsor
- GERCOR - Multidisciplinary Oncology Cooperative Group
- Enrollment
- 44
- Locations
- 20
- Primary Endpoint
- Progression free survival (PFS)
- Last Updated
- 9 years ago
Overview
Brief Summary
Sunitinib may provide an opportunity for a novel therapeutic strategy for the treatment of subjects with neuroendocrine tumors.
Detailed Description
With the exception of surgery for localized disease, there is presently a lack of available therapies with proven survival benefit for patients with neuroendocrine tumors (NET). Available treatment options for unresectable disease include the use of somatostatin analogs, which may relieve symptoms related to hormonal hypersecretion. The efficacy of cytotoxic chemotherapy in patients with metastatic carcinoid tumors is also limited. Combinations of either streptozocin and cyclophosphamide, or streptozocin and 5-fluorouracil, appear to be inactive, and both regimens are associated with substantial toxicity. Receptor tyrosine kinases (RTKs) are implicated in deregulated/ autocrine proliferation and survival of solid and hematologic cancer cells. Sunitinib malate is an orally administered small molecule that inhibits the tyrosine kinase enzymatic activities of the receptors for VEGF and PDGF, and also blocks signalling through the KIT, FLT3 and RET pathways. Therefore, sunitinib malate may provide an opportunity for a novel therapeutic strategy for the treatment of subjects with NET.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with midgut well-differentiated Grade 1-2 endocrine tumor.
- •Local, locally advanced or metastatic disease documented as progressive by RECIST v1.
- •on CT-scan or MRI at baseline and within 12 months prior to baseline.
- •5HIAA levels superior to 1.5ULN as measured in each individual centre.
- •Disease that is not amenable to surgery with curative intent.
- •Presence of at least one measurable target lesion for further evaluation according to RECIST v1.1
- •Adequate organ function
- •ECOG Performance status 0 or
- •Life expectancy superior or equal to 3 months.
- •Age superior or equal to 18 years.
Exclusion Criteria
- •Patients with undifferentiated, poorly differentiated gastrointestinal neuroendocrine tumors, pancreatic neuroendocrine tumors, bronchial carcinoid tumors.
- •Patients with carcinoid tumors with the presence of an obstructive intestinal tumor.
- •Patients with uncontrolled cardiac complication as part of their carcinoid syndrome.
- •Current treatment with any chemotherapy, chemoembolization therapy, immunotherapy, or investigational anticancer agent
- •Current treatment with dose superior or equal to 120 mg per month of lanreotide
- •Prior treatment with any tyrosine kinase inhibitors or anti-VEGF angiogenic inhibitors. Prior treatment with non-VEGF-targeted angiogenic inhibitors such as everolimus or temsirolimus is permitted.
- •Patients who stopped everolimus treatment was less than 4 weeks prior to randomization.
- •Patients with concomitant treatment with interferon.
- •Patients previously treated with chemotherapy, loco-regional therapy (e.g., chemoembolization) or interferon with last administration less than 6 weeks prior to randomization or with toxicity not resolved to less or equal grade 1 at randomization.
- •Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri.
Arms & Interventions
Sunitinib
Sunitinib 37.5 mg daily. Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.
Intervention: Lanreotide
Sunitinib
Sunitinib 37.5 mg daily. Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.
Intervention: Sunitinib
Placebo
Placebo (for sunitinib). Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.
Intervention: Lanreotide
Placebo
Placebo (for sunitinib). Lanreotide at the dose of 120 mg will be injected every 28 days as the reference treatment to control the carcinoid syndrome in both arms.
Intervention: Placebo (for sunitinib)
Outcomes
Primary Outcomes
Progression free survival (PFS)
Time Frame: time from date of randomization to first progression of disease (PD) or death for any reason in the absence of documented PD, assessed up to 3 years after the beginning of the study
To evaluate the efficacy of the combination of sunitinib malate with lanreotide acetate and of placebo with lanreotide acetate regarding progression-free-survival (PFS) as assessed by the investigator, in patients suffering from progressive, advanced/metastatic midgut carcinoid tumors.
Secondary Outcomes
- Quality of life(From screening to 1 month after last study drug administration, assessed up to 3 years after the beginning of the study)
- Objective response (OR)(from randomization until disease progression, assessed up to 3 years after the beginning of the study)
- Safety(from visit 1 to 1 month after last study drug administration, assessed up to 3 years after the beginning of the study)
- Overall survival (OS)(time from date of randomization to date of death, assessed up to 3 years after the beginning of the study)
- Duration of response (DR)(time from CR or PR to objective tumor progression or to death due to any cause, whichever occurs first, assessed up to 3 years after the beginning of the study)
- Time to tumor response (TTR)(time from date of randomization to first documentation of objective tumor response that is subsequently confirmed.assessed up to 3 years after the beginning of the study)
- Biological responses(from baseline to end of treatment, assessed up to 3 years after the beginning of the study)