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LBH589 Treatment for Refractory Clear Cell Renal Carcinoma

26 octobre 2021 mis à jour par: SCRI Development Innovations, LLC

A Phase II Study of LBH589 in the Treatment of Patients With Refractory Clear Cell Renal Carcinoma

Inhibition of histone deacetylase (HDAC) provides a novel approach for cancer treatment. LBH589, an oral HDAC inhibitor, has been well tolerated in phase I trials and has shown activity against several types of cancer. In this nonrandomized phase II trial, we are investigating the activity of LBH589 in the treatment of patients with refractory clear cell renal carcinoma.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

Inhibition of histone deacetylase (HDAC) provides a potential target for cancer treatment. Histones are components of the core proteins of nucleosomes, and acetylation and deacetylation of these proteins play a role in the regulation of gene expression. HDAC activity is known to be increased in many types of malignant cells; HDAC inhibitors have been shown to induce differentiation, cell cycle arrest, and apoptosis in cultured tumor cells. Since this tumor-associated mechanism is common to many types of cancer, HDAC may have a broad role in cancer treatment.

Type d'étude

Interventionnel

Inscription (Réel)

20

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • États-Unis
    • Florida
      • Fort Myers, Florida, États-Unis, 33901
        • Florida Cancer Specialists
    • Georgia
      • Gainesville, Georgia, États-Unis, 30501
        • Northeast Georgia Medical Center
    • Louisiana
      • Baton Rouge, Louisiana, États-Unis, 70806
        • Baton Rouge General Medical Center
    • Maryland
      • Bethesda, Maryland, États-Unis, 20817
        • Center for Cancer and Blood Disorders
    • Nebraska
      • Omaha, Nebraska, États-Unis, 68114
        • Methodist Cancer Center
    • New Jersey
      • Morristown, New Jersey, États-Unis, 07960
        • Hematology Oncology Associates of Northern NJ
    • Ohio
      • Cincinnati, Ohio, États-Unis, 45242
        • Oncology Hematology Care
    • Tennessee
      • Chattanooga, Tennessee, États-Unis, 37404
        • Chattanooga Oncology Hematology Associates
      • Nashville, Tennessee, États-Unis, 37023
        • Tennessee Oncology, PLLC
    • Virginia
      • Newport News, Virginia, États-Unis, 23601
        • Peninsula Cancer Institute

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Histologically documented metastatic or locally unresectable clear cell renal carcinoma. In patients with mixed histologies, the clear cell component must comprise > 75% of the cancer.
  • Documented disease progression or intolerance while receiving treatment with: a) sunitinib, sorafenib, or both, and b) temsirolimus.
  • Maximum of 4 prior systemic regimens allowed and may include other targeted agents, immunotherapy and chemotherapy.
  • Measurable disease by RECIST criteria.
  • ECOG PS 0 or 1.
  • Laboratory values as follows: ANC >= 1500/μL, Hgb >= 9 g/dL, Platelets >= 100,000/uL, AST/SGOT and ALT/SGPT <= 2.5 x ULN or <= 5.0 x ULN in patients with liver metastases, Creatinine <= 2.0 mg/dL Or Calculated Creatinine Clearance >= 50 ml/min, Albumin >= 3 g/dL, Potassium >= lower limit normal (LLN),Phosphorous >= LLN, Calcium >= LLN, Magnesium > LLN
  • Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment.
  • Life expectancy > 12 weeks.
  • Accessible for treatment and follow-up.
  • All patients must be able to understand the nature of the study and give written informed consent prior to study entry.

Exclusion Criteria:

  • Age < 18 years of age.
  • Prior treatment with an HDAC inhibitor.
  • Impaired cardiac function
  • Ongoing therapy with antiarrhythmics or other medications associated with QTc prolongation.
  • Uncorrected hypokalemia or hypomagnesemia.
  • Uncontrolled hypertension or cardiac arrhythmias.
  • Active parenchymal brain metastases. Patients who have had brain metastases resected, or have received radiation therapy ending > 8 weeks prior to study entry are eligible if they meet all of the following criteria: 1) residual neurologic symptoms < grade 1, 2) no dexamethasone requirement, 3) follow-up MRI shows regression of lesions after treatment, with no new lesions appearing.
  • Active meningeal metastases.
  • Known diagnosis of human immunodeficiency virus (HIV) infection.
  • Unresolved diarrhea > CTCAE grade 1.
  • Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors.
  • Chemotherapy, investigational drug therapy, major surgery < 4 weeks prior to starting study drug or patients that have not recovered from side effects of previous therapy.
  • Patient is < 5 years free of another primary malignancy except if the other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
  • Concomitant use of any anti-cancer therapy or radiation therapy.
  • Pregnant or breast feeding or female of reproductive potential not using 2 effective methods of birth control.
  • Male patients whose sexual partners are women of childbearing potential not using effective birth control.
  • Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease.
  • Other concurrent severe, uncontrolled infection or intercurrent illness
  • Abnormal thyroid function (TSH or free T4) detected at screening. Patients with known hypothyroidism who are stable on thyroid replacement are eligible.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Autre: Treatment
LBH589 will be administered orally at a dose of 45 mg (1 - 5 mg capsule and 2 - 20 mg capsules) on Monday and Thursday of each week (twice weekly). To enable patients to undergo cardiac monitoring, all patients must begin treatment on a Monday, and continue Monday/Thursday dosing during subsequent treatment cycles. Patients with objective response or stable disease after re-evaluation at week 8 will continue LBH589 at the same dose until disease progression, unacceptable toxicity and/or at the discretion of the investigator.
Médicament: LBH589
LBHLBH589 will be administered orally at a dose of 45 mg (1 - 5 mg capsule and 2 - 20 mg capsules) on Monday and Thursday of each week (twice weekly). To enable patients to undergo cardiac monitoring (Section 3.5.2), all patients must begin treatment on a Monday, and continue Monday/Thursday dosing during subsequent treatment cycles.
Autres noms:
  • Panobinostat

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Progression-free Survival
Délai: 18 months
Progression-free survival was defined as the interval from the date of first treatment with panobinostat until the date that disease progression or death occurred. Progressive disease (PD): 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm.
18 months

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Number of Participants Experiencing ≥Grade 2 Adverse Events
Délai: 18 months
An adverse event (AE) is the development of an undesirable medical condition, or the deterioration of a preexisting medical condition (other than the condition that is being treated by the trial) following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. The number of participants experiencing such adverse events that are related to the study drug are reported here.
18 months
Number of Participants With Overall Response
Délai: 18 months

Response was evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Overall response is defined as the proportion of participants whose disease either decreased (partial response- PR) or disappeared (Complete response - CR).

Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD
18 months

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

SCRI Development Innovations, LLC

Collaborateurs

Novartis

Les enquêteurs

  • Chaise d'étude: John D. Hainsworth, M.D., SCRI Development Innovations, LLC

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 janvier 2008

Achèvement primaire (Réel)

1 mars 2010

Achèvement de l'étude (Réel)

1 juin 2010

Dates d'inscription aux études

Première soumission

26 octobre 2007

Première soumission répondant aux critères de contrôle qualité

26 octobre 2007

Première publication (Estimation)

29 octobre 2007

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

23 novembre 2021

Dernière mise à jour soumise répondant aux critères de contrôle qualité

26 octobre 2021

Dernière vérification

1 octobre 2021

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • SCRI GU 49

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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