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

Primary Purpose

Solid Tumors, Bladder Cancer

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Cisplatin

Carboplatin

About this trial

This is an interventional treatment trial for Solid Tumors focused on measuring advanced solid tumors, bladder cancer, gemcitabine, cisplatin, carboplatin, solid tumors

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Icahn School of Medicine at Mount Sinai

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Cisplatin

Carboplatin

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Recommended phase II dose of combination regimen

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

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.

Full Information

NCT ID

NCT01496534

First Posted

December 12, 2011

Last Updated

November 26, 2013

Sponsor

Matthew Galsky

Collaborators

Novartis

1. Study Identification

Unique Protocol Identification Number

NCT01496534

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2013

Overall Recruitment Status

Terminated

Why Stopped

toxicity of combination of medications

Study Start Date

January 2012 (undefined)

Primary Completion Date

September 2013 (Actual)

Study Completion Date

September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Matthew Galsky

Collaborators

Novartis

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Solid Tumors, Bladder Cancer

Keywords

advanced solid tumors, bladder cancer, gemcitabine, cisplatin, carboplatin, solid tumors

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cisplatin

Arm Type

Active Comparator

Arm Description

Arm Title

Carboplatin

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Other Intervention Name(s)

TKI258

Intervention Description

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Other Intervention Name(s)

TKI258

Intervention Description

Primary Outcome Measure Information:

Title

Recommended phase II dose of combination regimen

Description

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.

Time Frame

Within the first 21 days of treatment

Secondary Outcome Measure Information:

Title

Antitumor activity

Description

Time Frame

After every 2 cycles (42 days) of combination therapy up to 3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Matthew D. Galsky, M.D.

Organizational Affiliation

Icahn School of Medicine at Mount Sinai

Official's Role

Principal Investigator

Facility Information:

Facility Name

Icahn School of Medicine at Mount Sinai

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

20094046

Citation

Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010 Feb;10(2):116-29. doi: 10.1038/nrc2780.

Results Reference

background

PubMed Identifier

18241002

Citation

Knowles MA. Novel therapeutic targets in bladder cancer: mutation and expression of FGF receptors. Future Oncol. 2008 Feb;4(1):71-83. doi: 10.2217/14796694.4.1.71.

Results Reference

background

PubMed Identifier

18381947

Citation

Sarker D, Molife R, Evans TR, Hardie M, Marriott C, Butzberger-Zimmerli P, Morrison R, Fox JA, Heise C, Louie S, Aziz N, Garzon F, Michelson G, Judson IR, Jadayel D, Braendle E, de Bono JS. A phase I pharmacokinetic and pharmacodynamic study of TKI258, an oral, multitargeted receptor tyrosine kinase inhibitor in patients with advanced solid tumors. Clin Cancer Res. 2008 Apr 1;14(7):2075-81. doi: 10.1158/1078-0432.CCR-07-1466.

Results Reference

background

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

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