Advanced Incurable Solid MalignancyPhase 1NCT00660725
Study of GemOx and Vandetanib in Advanced Solid Malignancy
A Phase 1 study testing Vandetanib, Gemcitabine and Oxaliplatin in people with Advanced Incurable Solid Malignancy, run by Leonard Appleman at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Incurable Solid Malignancy
- What is being tested?
- Vandetanib, Gemcitabine and Oxaliplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2009to Dec 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.)
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- 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
- Previous enrollment or randomization of treatment in the present study
- Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy
- Peripheral neuropathy grade 2 or of greater severity of any cause
- More than 2 prior systemic chemotherapy regimens for advanced stage disease. Prior adjuvant chemotherapy will not count as a prior regimen.
- Known severe hypersensitivity to vandetanib or any of the excipients of these products.
- Previous or current malignancies of other histologies within the last 5 years, with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin.
- Concomitant medications that are potent inducers (rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital and St. John's Wort) of CYP3A4 function.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Cancer Institute / Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: An Open Label Phase I Study of Gemcitabine/Oxaliplatin (GEMOX) and Vandetanib (ZACTIMA; ZD6474) Combination in Patients With Advanced Solid Malignancy (IRUSZACT0070) (UPCI 07-025)
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.
Read the detailed description
This is a Phase I, open-label, dose-escalating, non-randomized study of the safety and tolerability of vandetanib in combination with a fixed dose of gemcitabine and oxaliplatin (GemOx) in the treatment of patients with advanced solid malignancy. EGFR is an important target for therapeutic drug development. It is widely expressed in most cancers and has a vital role in the regulation of proliferation signals. EGFR is expressed in a high degree (>80%) of pancreatic tumors and is a rational target for therapy. Vandetanib selectively inhibits EGFR tyrosine kinase activity and VEGF-2 receptor. It has good oral bioavailability and has growth inhibitory activity in a wide variety of human cell lines including cells with acquired resistance to other EGFR inhibitors. The growth inhibitory property of vandetanib in vivo correlates more with its anti VEGF property, especially in cell lines with acquired resistance to EGFR inhibition. The combination of gemcitabine and oxaliplatin (GEMOX) is a well-established regimen that has demonstrated encouraging antitumor activity in pancreaticobiliary cancers in phase II studies. Recent clinical trials have also shown activity in hepatobiliary and germ cell tumors. The combination of vandetanib and gemcitabine has potential advantages and may result in an additive or synergistic effect. The GEMOX regimen is well tolerated, and toxicity does not overlap with the most common toxicity of rash or diarrhea observed with vandetanib. Thus, the combination of vandetanib and GEMOX is expected to be a well tolerated, and an easily administered regimen with improved efficacy and no overlapping toxicities.
- Conditions
- Advanced Incurable Solid Malignancy
- Being tested
- Vandetanib, Gemcitabine, Oxaliplatin
- Keywords
- Gemcitabine, Oxaliplatin, Vandetanib, Phase I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VandetanibDrug
Also called Zactima, ZD6474
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.
GemcitabineDrug
Also called Gemzar®
30-minute IV infusion of 1000 mg/m^2 gemcitabine on Day 1 of each 14-day cycle.
OxaliplatinDrug
Also called Eloxatin®
Immediately following gemcitabine IV: 2-hour IV infusion of 85 mg/m^2 oxaliplatin on Day 1 of each 14-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Vandetanib; Drug: Gemcitabine; Drug: Oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Radiologic imaging is done every 6-7 weeks for disease assessment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2008 (estimated)
- Study startFeb 2009
- Primary completionNov 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Incurable Solid MalignancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leonard Appleman
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor-investigator, Leonard Appleman, University of Pittsburgh
- Investigators
- Leonard J. Appleman, M.D., Ph.D., Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00660725
- Sponsor's protocol ID
- 07-025
- Other IDs
- IRUSZACT0070, UPCI 07-025
- Status last verified
- Jan 2014
- First submitted
- 8 Apr 2008
- Last updated
- 23 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Phase I Study of Gemcitabine/Oxaliplatin (GEMOX) and Vandetanib (ZACTIMA; ZD6474) Combination in Patients With Advanced Solid Malignancy (IRUSZACT0070) (UPCI 07-025)
- ClinicalTrials.gov ID
- NCT00660725
- Acronym / sponsor ID
- 07-025
- Conditions
- Advanced Incurable Solid Malignancy
- Keywords
- Gemcitabine, Oxaliplatin, Vandetanib, Phase I
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Leonard ApplemanUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Feb 2009
- Primary completion
- Nov 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 17 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a Phase I, open-label, dose-escalating, non-randomized study of the safety and tolerability of vandetanib in combination with a fixed dose of gemcitabine and oxaliplatin (GemOx) in the treatment of patients with advanced solid malignancy. EGFR is an important target for therapeutic drug development. It is widely expressed in most cancers and has a vital role in the regulation of proliferation signals. EGFR is expressed in a high degree (>80%) of pancreatic tumors and is a rational target for therapy. Vandetanib selectively inhibits EGFR tyrosine kinase activity and VEGF-2 receptor. It has good oral bioavailability and has growth inhibitory activity in a wide variety of human cell lines including cells with acquired resistance to other EGFR inhibitors. The growth inhibitory property of vandetanib in vivo correlates more with its anti VEGF property, especially in cell lines with acquired resistance to EGFR inhibition. The combination of gemcitabine and oxaliplatin (GEMOX) is a well-established regimen that has demonstrated encouraging antitumor activity in pancreaticobiliary cancers in phase II studies. Recent clinical trials have also shown activity in hepatobiliary and germ cell tumors. The combination of vandetanib and gemcitabine has potential advantages and may result in an additive or synergistic effect. The GEMOX regimen is well tolerated, and toxicity does not overlap with the most common toxicity of rash or diarrhea observed with vandetanib. Thus, the combination of vandetanib and GEMOX is expected to be a well tolerated, and an easily administered regimen with improved efficacy and no overlapping toxicities.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vandetanib/GEMOX | Other | Drug: Vandetanib, Drug: Gemcitabine, Drug: OxaliplatinAll 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VandetanibAlso: Zactima, ZD6474Vandetanib 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. | Drug | Vandetanib/GEMOX |
| GemcitabineAlso: Gemzar®30-minute IV infusion of 1000 mg/m^2 gemcitabine on Day 1 of each 14-day cycle. | Drug | Vandetanib/GEMOX |
| OxaliplatinAlso: Eloxatin®Immediately following gemcitabine IV: 2-hour IV infusion of 85 mg/m^2 oxaliplatin on Day 1 of each 14-day cycle. | Drug | Vandetanib/GEMOX |
Primary outcome
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
Time frame: 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.
1 secondary outcome
To document clinical responses and to identify time to progression (TTP) of each patient compared to TTP on prior therapy
Time frame: Radiologic imaging is done every 6-7 weeks for disease assessment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leonard J. Appleman, M.D., Ph.D. principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vandetanib, Gemcitabine and Oxaliplatin in people with Advanced Incurable Solid Malignancy, run by Leonard Appleman at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2014.