Clinical Trials Logo

Clinical Trial Summary

This randomized phase I/II clinical trial is studying the side effects and best dose of gamma-secretase/notch signalling pathway inhibitor RO4929097 when given together with vismodegib and to see how well they work in treating patients with advanced or metastatic sarcoma. Vismodegib may slow the growth of tumor cells. Gamma-secretase/notch signalling pathway inhibitor RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vismodegib together with gamma-secretase/notch signalling pathway inhibitor RO4929097 may be an effective treatment for sarcoma.


Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose (MTD) of gamma-secretase inhibitor RO4929097 (RO4929097) when given in combination with fixed-dose Hedgehog antagonist GDC-0449 (GDC-0449) which will become the recommended dose for the phase II portion of this study. (Phase Ib) II. To assess the progression-free survival (PFS) of the combination of RO4929097 with and without GDC-0449 in two arms of patients with advanced sarcoma. (Phase II)

SECONDARY OBJECTIVES:

I. To describe the tolerability and adverse event profile of daily GDC-0449 administered orally in combination with daily RO4929097 administered orally for 21 consecutive days. (Phase Ib) II. To describe the pharmacokinetics of the combination of the combination of GDC-0449 and RO4929097. (Phase Ib) III. To assess Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 overall response rates (complete and partial response [CR+PR]) for combination therapy. (Phase Ib and II) IV. To conduct pharmacodynamic studies in tissue biopsies (pre- and post-study) for explorative and hypothesis-generating studies. (Phase Ib and II) V. To assess overall survival. (Phase II) VI. To further describe the pharmacokinetics and pharmacodynamics of the combination of GDC-0449 and RO4929097 at the phase II dose at the continuous schedule. (Phase II) V. To conduct pharmacodynamic studies in tissue biopsies (pre- and post- study drug[s]) for explorative and hypothesis generating studies. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of gamma-secretase/notch signalling pathway inhibitor RO4929097 followed by a phase II study.

PHASE IB:

PART A: Patients receive vismodegib orally (PO) once daily (QD) on days 1-21.

PART B: Beginning within 7 days of finishing part A, patients receive vismodegib PO and gamma-secretase/notch signalling pathway inhibitor RO4929097 PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive gamma-secretase/notch signalling pathway inhibitor RO4929097 PO QD on days 1-21.

ARM II: Patients receive vismodegib PO and gamma-secretase/notch signalling pathway inhibitor RO4929097 PO QD on days 1-21.

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks. ;


Study Design


Related Conditions & MeSH terms

  • Adult Alveolar Soft Part Sarcoma
  • Adult Angiosarcoma
  • Adult Desmoplastic Small Round Cell Tumor
  • Adult Epithelioid Hemangioendothelioma
  • Adult Epithelioid Sarcoma
  • Adult Extraskeletal Myxoid Chondrosarcoma
  • Adult Extraskeletal Osteosarcoma
  • Adult Fibrosarcoma
  • Adult Leiomyosarcoma
  • Adult Liposarcoma
  • Adult Malignant Mesenchymoma
  • Adult Malignant Peripheral Nerve Sheath Tumor
  • Adult Rhabdomyosarcoma
  • Adult Synovial Sarcoma
  • Adult Unclassified Pleomorphic Sarcoma
  • Chondrosarcoma
  • Clear Cell Sarcoma of the Kidney
  • Conjunctival Kaposi Sarcoma
  • Dermatofibrosarcoma
  • Dermatofibrosarcoma Protuberans
  • Desmoplastic Small Round Cell Tumor
  • Fibrosarcoma
  • Gastrointestinal Stromal Tumor
  • Gastrointestinal Stromal Tumors
  • Hemangioendothelioma
  • Histiocytoma, Malignant Fibrous
  • Leiomyosarcoma
  • Liposarcoma
  • Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Metastatic Osteosarcoma
  • Neoplasms
  • Nerve Sheath Neoplasms
  • Neurilemmoma
  • Neuroectodermal Tumors
  • Neuroectodermal Tumors, Primitive
  • Neuroectodermal Tumors, Primitive, Peripheral
  • Osteosarcoma
  • Ovarian Sarcoma
  • Recurrent Adult Soft Tissue Sarcoma
  • Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone
  • Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Recurrent Kaposi Sarcoma
  • Recurrent Osteosarcoma
  • Recurrent Uterine Corpus Sarcoma
  • Rhabdomyosarcoma
  • Sarcoma
  • Sarcoma, Alveolar Soft Part
  • Sarcoma, Clear Cell
  • Sarcoma, Ewing
  • Sarcoma, Kaposi
  • Sarcoma, Synovial
  • Small Intestine Leiomyosarcoma
  • Stage III Adult Soft Tissue Sarcoma
  • Stage III Uterine Sarcoma
  • Stage IV Adult Soft Tissue Sarcoma
  • Stage IV Uterine Sarcoma
  • Unclassified Pleomorphic Sarcoma of Bone

NCT number NCT01154452
Study type Interventional
Source National Cancer Institute (NCI)
Contact
Status Completed
Phase Phase 1/Phase 2
Start date June 2010
Completion date February 2015

See also
  Status Clinical Trial Phase
Recruiting NCT04933669 - Prospective Multicenter Clinical Study of Neoadjuvant Imatinib Mesylate for Gastrointestinal Stromal Tumors Phase 2
Completed NCT01769248 - Prospective Trial of EUS-FNA Versus EUS-FNB Using a Novel Core Biopsy Needle N/A
Completed NCT01774162 - EUS-guided Fine Needle Biopsy With a New Core Histology Needle Versus Conventional Fine Needle Aspiration N/A
Completed NCT01110668 - Evaluation of Nilotinib In Patients With Advanced Gastrointestinal Stromal Tumor (GIST) Phase 2
Terminated NCT00091078 - Oblimersen and Imatinib Mesylate in Treating Patients With Advanced Gastrointestinal Stromal Tumors That Cannot Be Removed By Surgery Phase 2
Completed NCT00025246 - Imatinib Mesylate in Treating Patients With Gastrointestinal Stromal Tumor That Has Been Completely Removed During Surgery Phase 2
Active, not recruiting NCT00265798 - Sorafenib in Treating Patients With Malignant Gastrointestinal Stromal Tumor That Progressed During or After Previous Treatment With Imatinib Mesylate and Sunitinib Malate Phase 2
Recruiting NCT04143048 - A Study on Non-invasive Early Diagnosis of Gastrointestinal Stromal Tumors and Differentiation of Benign and Malignant Nodules
Recruiting NCT02931981 - Serum Dickkopf-4 as a Biomarker for the Diagnosis and Treatment of Gastrointestinal Stromal Tumor N/A
Not yet recruiting NCT02576080 - Efficacy of Imatinib in Patients With Intermediate-risk Gastrointestinal Stromal Tumor With a High-risk Genomic Grade Index Phase 3
Recruiting NCT01389583 - A Study of AUY922 for GIST(Gastrointestinal Stromal Tumor) Patients Phase 2
Recruiting NCT00777504 - Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors Phase 4
Completed NCT00764595 - Imatinib Mesylate in Treating Patients With Liver Metastasis From a Gastrointestinal Stromal Tumor Phase 2
Completed NCT00769782 - Surgery in Treating Patients With Liver Metastasis From a Gastrointestinal Stromal Tumor Phase 2
Completed NCT00098579 - Doxorubicin Hydrochloride and Alvocidib in Treating Patients With Metastatic or Recurrent Sarcoma That Cannot Be Removed By Surgery Phase 1
Completed NCT00005862 - SU5416 in Treating Patients With Advanced, Metastatic, or Recurrent Soft Tissue Sarcomas Phase 2
Completed NCT00004895 - Octreotide as Palliative Therapy for Cancer-Related Bowel Obstruction That Cannot Be Removed by Surgery Phase 2
Recruiting NCT02776878 - A Clinical Trial Evaluating the Efficacy and Safety of Dasatinib in Refractory Metastatic GIST N/A
Completed NCT01751919 - A Clinical Trial to Compare the Pharmacokinetics of Imatinib Mesylate Tablet 400mg (1 Tablet) and Glivec Film-coated Tablet 100mg (4 Tablets)(Phase I) Phase 1
Completed NCT01267695 - Perioperative Imatinib Mesylate in Treating Patients With Locally Advanced Gastrointestinal Stromal Tumor Phase 2