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

NCT01496534 | Terminated Phase 1

• 1 other identifier: GCO 11-0946
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumors; Bladder Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Within the first 21 days of treatment

Secondary Outcomes (1)

• Antitumor activity

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

Study Arms (2)

Cisplatin

ACTIVE COMPARATOR

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

Carboplatin

ACTIVE COMPARATOR

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

Interventions

Cisplatin DRUG

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

Also known as: TKI258

Cisplatin

Carboplatin DRUG

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

Also known as: TKI258

Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Matthew Galsky: lead
• Novartis: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (3)

• 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.

  PMID: 20094046 BACKGROUND

• 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.

  PMID: 18241002 BACKGROUND

• 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.

  PMID: 18381947 BACKGROUND

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Cisplatin; 4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; Carboplatin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Matthew D. Galsky, M.D.

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 12, 2011
• First Posted: December 21, 2011
• Study Start: January 1, 2012
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: November 27, 2013

Record last verified: 2013-11

Locations

US (1)