Study of GemOx and Vandetanib in Advanced Solid Malignancy

NCT00660725 | Completed Phase 1 DMC

• 3 other identifiers: 07-025IRUSZACT0070UPCI 07-025
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study that will try to find the highest and safest dose of an experimental drug, vandetanib, that can be given in combination with two standard chemotherapy agents, gemcitabine and oxaliplatin, to subjects with advanced solid malignancies.

Conditions

Advanced Incurable Solid Malignancy

Keywords

Gemcitabine; Oxaliplatin; Vandetanib; Phase I

Outcome Measures

Primary Outcomes (1)

• To establish the Maximum Tolerated Dose (MTD) and toxicities of vandetanib (Zactima; ZD6474) in combination with fixed dose of GEMOX (gemcitabine/oxaliplatin) and to establish the recommended phase II dose of the GEMOX and vandetanib regimen

  The MTD (and recommended phase II dose) is defined as the highest dose at which <2 of 6 patients experience DLT. The observation period for DLT is the first cycle of therapy.

Secondary Outcomes (1)

• To document clinical responses and to identify time to progression (TTP) of each patient compared to TTP on prior therapy

  Radiologic imaging is done every 6-7 weeks for disease assessment

Study Arms (1)

Vandetanib/GEMOX

OTHER

All subjects receive the same combination study drug and follow the same study schedule. As a phase 1 study, only the doses will vary between subjects.

Drug: Vandetanib; Drug: Gemcitabine; Drug: Oxaliplatin

Interventions

Vandetanib DRUG

Vandetanib is a pill that will be self-administered orally on Days 1-14 of each 14-day cycle. The dose of vandetanib each subject will receive will be determined by a dose escalation schedule (either 200 mg or 300 mg per day), which will be followed to determine the MTD of the study drug combination (vandetanib + GemOx). In the absence of disease progression, unacceptable toxicities, or other complications, the vandetanib and GemOx combination may continue per protocol for a maximum of 6 cycles, or 12 weeks. In subjects who show response or stable disease, vandetanib may be continued as a single agent beyond the 6 cycle maximum, at the investigator's discretion.

Also known as: Zactima, ZD6474

Vandetanib/GEMOX

Gemcitabine DRUG

30-minute IV infusion of 1000 mg/m\^2 gemcitabine on Day 1 of each 14-day cycle.

Also known as: Gemzar®

Vandetanib/GEMOX

Oxaliplatin DRUG

Immediately following gemcitabine IV: 2-hour IV infusion of 85 mg/m\^2 oxaliplatin on Day 1 of each 14-day cycle.

Also known as: Eloxatin®

Vandetanib/GEMOX

Eligibility Criteria

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

You may qualify if:

• Patients with advanced incurable solid malignancy who are likely to benefit from GEMOX therapy.
• Provision of informed consent prior to any study procedures.
• Females and males age ≥18 years
• Histological/cytological confirmation of malignancy
• Negative pregnancy test for women of childbearing potential
• ECOG performance status of 0 or 1
• Ability to take oral medications without difficulty
• Adequate bone marrow function: ANC \>1500/L and platelet count \>100,000/dL
• Adequate hepatic function: Total Bilirubin ≤ 1.5 x ULN, ALT/AST ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastasis), ALP ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastasis)
• Serum calcium in normal range (ionized or adjusted for albumin), Serum magnesium in normal range, Serum Potassium ≥ 4.0 mmol/L. Supplementation allowed.
• Serum Cr \< 1.5 x UNL or Creatinine Clearance ≥ 50 mL/min calculated by Cockcroft-Gault formula
• Men and women of childbearing potential must be willing to practice acceptable methods of birth control.
• Patients with brain metastasis should have received appropriate therapy and have stable disease at least 4 weeks after radiotherapy/surgery.
• Subjects should have recovered from side effects of prior therapy to grade 1 or less

You may not qualify if:

• Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.
• Clinically significant cardiovascular event (e.g. myocardial infarction, superior vena cava syndrome (SVC), New York Heart Association (NYHA) classification of heart disease ≥2 within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
• History of arrhythmia (multifocal premature ventricular contractions PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded.
• Previous history of QTc prolongation with other medications that required discontinuation of that medication.
• Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age.
• Presence of left bundle branch block (LBBB.)
• QTc with Bazett's correction that is unmeasurable, or ≥480 msec on screening ECG. (Note: If a subject has a QTc interval ≥480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be \<480 msec in order for the subject to be eligible for the study.) Patients who are receiving a drug that has a risk of QTc prolongation are excluded if QTc is ≥ 460 msec.
• Any concurrent medication that may cause QTc prolongation or induce Torsades de Pointes.
• Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg)
• Currently active diarrhea that may affect the ability of the patient to absorb the vandetanib or tolerate diarrhea.
• Women who are currently pregnant or breast feeding.
• Receipt of any investigational agents within 30 days or commercially available agents within 21 days prior to commencing study treatment
• Last dose of prior chemotherapy discontinued less than 4 weeks before the start of study therapy
• Last radiation therapy within the last 4 weeks before the start of study therapy, except palliative radiotherapy for less than 12 fractions
• Any unresolved toxicity greater than CTCAE grade 1 from previous anti-cancer therapy

Sponsors & Collaborators

• Leonard Appleman: lead
• AstraZeneca: collaborator

Study Sites (1)

University of Pittsburgh Cancer Institute / Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Interventions

vandetanib; Gemcitabine; Oxaliplatin

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Leonard J. Appleman, M.D., Ph.D.

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 8, 2008
• First Posted: April 17, 2008
• Study Start: February 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: December 1, 2010
• Last Updated: January 23, 2014

Record last verified: 2014-01

Locations

US (1)