Phase Ib Study of Gemcitabine Plus Cisplatin or Carboplatin Plus Dovitinib in Patients With Advanced Solid Tumors

This study has been terminated.
(toxicity of combination of medications)
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Matthew Galsky, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01496534
First received: December 12, 2011
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

This is a phase Ib dose escalation study of dovitinib given in combination with either gemcitabine plus cisplatin or carboplatin in patients with advanced solid tumors. Patients with advanced solid tumors, for whom treatment with gemcitabine plus cisplatin or carboplatin would otherwise be warranted, will be enrolled. The dose of dovitinib will be escalated in successive cohorts using standard "3+3" dose escalation rules. Patients will continue treatment, in the absence of prohibitive toxicity, until disease progression. The study will define the recommended phase II dose of these combination regimens.


Condition Intervention Phase
Solid Tumors
Bladder Cancer
Drug: Cisplatin
Drug: Carboplatin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase Ib Study of Dovitinib in Combination With Gemcitabine Plus Cisplatin or Gemcitabine Plus Carboplatin in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Recommended phase II dose of combination regimen [ Time Frame: Within the first 21 days of treatment ] [ Designated as safety issue: Yes ]
    The primary objectives of this study are to determine the recommended phase II dose of dovitinib given in combination with gemcitabine plus carboplatin or cisplatin.


Secondary Outcome Measures:
  • Antitumor activity [ Time Frame: After every 2 cycles (42 days) of combination therapy up to 3 years ] [ Designated as safety issue: Yes ]
    A CT scan of the chest, abdomen, and pelvis will be performed after every 2 cycles (or sooner if there is evidence of disease progression) while on combination therapy until disease progression (eg, after cycle 2, after cycle 4, and after cycle 6). Response to treatment will be determined using RECIST.


Enrollment: 14
Study Start Date: January 2012
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cisplatin
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Cisplatin 70 mg/m2 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts.
Drug: Cisplatin
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Cisplatin 70 mg/m2 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts
Other Name: TKI258
Active Comparator: Carboplatin
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Carboplatin AUC 5 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts.
Drug: Carboplatin
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Carboplatin AUC 5 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts
Other Name: TKI258

Detailed Description:

This is a phase Ib study of dovitinib given in combination with gemcitabine plus cisplatin or carboplatin in patients with advanced solid tumors. This study will utilize standard 3+3 dose escalation rules to define the recommended phase II dose. Dose escalation will proceed independently in the two cohorts (cisplatin cohort: gemcitabine + cisplatin + dovitinib; carboplatin cohort: gemcitabine + carboplatin + dovitinib). Patients will receive treatment for up to 6 cycles, in the absence of toxicity, until disease progression

Primary Objective:

To determine the recommended phase II dose of dovitinib given in combination with gemcitabine plus cisplatin or carboplatin.

Secondary Objectives:

  • To determine the response rate to treatment as per Response Evaluation Criteria in Solid Tumors (RECIST)
  • To determine the toxicity of treatment at per the Common Terminology for Adverse Events (CTCAE v4)
  • To determine the pharmacokinetics of dovitinib in combination with gemcitabine plus cisplatin or carboplatin.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent and HIPAA authorization for release of personal health information.
  • Age ≥ 18 years at the time of consent.
  • Karnofsky Performance Status of ≥ 70%.
  • Advanced/metastatic solid tumor for which treatment with gemcitabine plus carboplatin or gemcitabine plus cisplatin would otherwise be warranted.
  • Prior treatment with chemotherapy is permitted. Patients must not have received more than three prior chemotherapeutic regimens.
  • Adequate organ function as determined by the following laboratory values:

    • Hemoglobin (Hgb) ≥ 9 g/dL
    • Platelets ≥ 100 x 109/L
    • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    • Creatinine of ≤ 1.5 OR Calculated creatinine clearance of ≥ 60 cc/min for the cisplatin cohort.

Calculated creatinine clearance of ≥ 30 cc/min for the carboplatin cohort.

  • Bilirubin ≤ 1.5 x ULN
  • Aspartate aminotransferase (AST, SGOT) ≤ 1.5 ULN
  • Alanine Aminotransferase (ALT, SGPT) < 1.5 ULN
  • INR ≤ 1.5 and a PTT within normal limits
  • LVEF assessed by 2-D echocardiogram (ECHO) > 50% or lower limit of normal or multiple gated acquisition scan (MUGA) > 45% or lower limit of normal

Exclusion Criteria:

  • Prior treatment with more than three prior chemotherapy regimens.
  • Has had major surgery within 30 days of starting the study treatment
  • Have active CNS metastases.
  • No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.
  • Prior cancer treatment must be completed at least 30 days prior to being registered for protocol therapy and the subject must have recovered from the acute toxic effects of the regimen.
  • Prior radiation therapy must be completed at least 30 days prior to being registered for protocol therapy.
  • Pregnant or breastfeeding.
  • Clinically significant infections as judged by the treating investigator.
  • Impaired cardiac function or clinically significant cardiac diseases
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
  • Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin
  • Women of child-bearing potential, who are biologically able to conceive, not employing two forms of highly effective contraception.
  • Fertile males not willing to use contraception
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01496534

Locations
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Sponsors and Collaborators
Matthew Galsky
Novartis
Investigators
Principal Investigator: Matthew D. Galsky, M.D. Mount Sinai School of Medicine
  More Information

Publications:
Responsible Party: Matthew Galsky, Principal Investigator, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01496534     History of Changes
Other Study ID Numbers: GCO 11-0946
Study First Received: December 12, 2011
Last Updated: November 26, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Mount Sinai School of Medicine:
advanced solid tumors
bladder cancer
gemcitabine
cisplatin
carboplatin
solid tumors

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Gemcitabine
Cisplatin
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 18, 2014