Colorectal CancerPhase 1NCT00660153
Study of Tivozanib (AV-951) Plus FOLFOX6 in Subjects With Advanced Colorectal Cancer and Other Gastrointestinal Cancers
A Phase 1 study testing Tivozanib (AV-951) plus FOLFOX6 in people with Colorectal Cancer and Gastrointestinal Cancer, run by AVEO Pharmaceuticals, Inc. at 2 sites in Netherlands.
Trial summary
The FOLFOX6 regimen is a standard chemotherapy regimen for the treatment of patients with colorectal cancer and other gastrointestinal cancers. Tivozanib (AV-951) is a targeted anti-angiogenesis agent that has demonstrated acceptable tolerability in a phase I clinical trial. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Gastrointestinal Cancer
- What is being tested?
- Tivozanib (AV-951) plus FOLFOX6
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesNetherlands
- Study dates
- Jun 2008to Jun 2012
- 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
- ≥ 18-year-old males or females
- Histologically or cytologically confirmed metastatic colorectal cancer or other gastrointestinal malignancy for which FOLFOX6 chemotherapy is a standard treatment. Other gastrointestinal cancers include, but are not limited to, esophageal, gastric, and small intestine, appendiceal, and pancreatico-biliary cancers.
- Documented progressive disease
- Measurable or evaluable disease by RECIST. (Note: Subjects enrolled in the MTD Expansion Cohort are required to have measurable disease, according to RECIST.)
- No more than 2 prior chemotherapy regimens for metastatic disease (This does not include prior adjuvant chemotherapy with fluorouracil and/or oxaliplatin.)
- At least 3 weeks since prior treatment with:
Show all 16Show fewer
- Chemotherapy (at least 6 weeks for nitrosoureas, mitomycin C, and liposomal doxorubicin)
- Agents targeting the VEGF pathway (eg, bevacizumab, sunitinib, sorafenib, etc.)
- Other signal transduction inhibitors and monoclonal antibodies
- Immunotherapy or biological response modifiers
- Systemic hormonal anti-cancer therapy, with the exception of LHRH agonists for prostate cancer
- Any experimental therapy
- Resolution of toxicities associated with prior chemotherapy to ≤ Grade 1 (except for Grade 2 alopecia)
- ECOG performance status ≤ 2 (see Appendix A) and life expectancy ≥ 3 months
- No childbearing potential or use of effective contraception by all fertile male and female subjects during the study and for 30 days after the last dose of study drug. All subjects must agree to use a highly effective method of contraception (including their partner). Effective birth control includes (a) IUD plus one barrier method; or (b) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm). Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
- Dated and signed informed consent
Who cannot join
- Primary CNS malignancies or clinically active CNS metastases
- Hematologic malignancies (includes leukemia in any form, lymphoma, and multiple myeloma)
- Any of the following hematologic abnormalities:
- Hemoglobin < 9.0 g/dL
- ANC < 1500 per mm3
- Platelet count < 100,000 per mm3
Show all 38Show fewer
- Any of the following serum chemistry abnormalities:
- Total bilirubin > 1.5 × ULN
- AST or ALT > 2.5 × ULN (or > 5 x ULN for subjects with liver metastasis)
- GGT > 2.5 x ULN (or > 5 x ULN for subjects with liver metastasis)
- Alkaline Phosphatase > 2.5 x ULN (or > 5 x ULN for subjects with liver or bone metastasis)
- Serum albumin < 3.0 g/dL
- Creatinine > 1.5 × ULN (or calculated CLCR <50 mL/min/1.73 m2)
- Proteinuria > 2.5 g/24 hours or 3+ with urine dipstick
- Any other ≥ Grade 3 laboratory abnormality at baseline (other than those listed above)
- Significant cardiovascular disease, including:
- Active clinically symptomatic left ventricular failure
- Active HTN (diastolic blood pressure > 100 mmHg). Subjects with a history of hypertension must have been on stable doses of anti-hypertensive drugs for ≥ 4 weeks prior to start of Cycle 1
- Uncontrolled hypertension: Blood pressure >140/90 mmHg on more than 2 antihypertensive medications
- Myocardial infarction within 3 months prior to start of Cycle 1
- Serious/active infection, or infection requiring parenteral antibiotics
- Inadequate recovery from any prior surgical procedure or major surgical procedure within 6 weeks prior to the start of Cycle 1
- Unhealed wounds, ulcers, or bone fractures
- Ongoing hemoptysis or history of clinically significant bleeding
- Cerebrovascular accident within 12 months prior to the start of Cycle 1, or peripheral vascular disease with claudication on walking less than 1 block
- Deep venous thrombosis or pulmonary embolus within 12 months prior to the start of Cycle 1 and/or ongoing need for full-dose oral or parenteral anticoagulation
- History of ≥ Grade 3 hypersensitivity reaction with prior exposure to oxaliplatin
- Subjects with a "currently active" second malignancy other than non-melanoma skin cancers or localized prostate cancer (with stable PSA for at least 3 months prior to the start of Cycle 1). Subjects are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy and are considered by their physician to be a < 30% risk of relapse.
- Life-threatening illness or organ system dysfunction compromising safety evaluation
- Uncontrolled psychiatric disorder or altered mental status precluding informed consent or necessary testing
- Inability to comply with protocol requirements
- Pregnant or lactating women
- Known concomitant genetic or acquired immune suppression disease, such as HIV
- Consumption of herbal preparations/supplements (except for a daily multivitamin/mineral supplement not containing herbal components) within 2 weeks prior to the start of Cycle 1
- Prior radiotherapy:
- Local radiation therapy (involving ≤ 25% of bone marrow) within 2 weeks prior to the start of Cycle 1
- Craniospinal radiotherapy within 3 months prior to the start of Cycle 1
- Radiotherapy to: whole abdomen or pelvis, whole lungs, > 25% of bone marrow, or total body irradiation within 6 months prior to the start of Cycle 1
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
University Medical Center Groningen; Internal Medicine, Department of Medical Oncology
Groningen
Erasmus Medical Center; Department of Medical Oncology
Rotterdam
About this study
Official title: A Phase 1b, Open-Label, Dose-Escalation Study of Tivozanib (AV-951) Plus FOLFOX6 in Subjects With Advanced Colorectal Cancer and Other Gastrointestinal Cancers
The FOLFOX6 regimen is a standard chemotherapy regimen for the treatment of patients with colorectal cancer and other gastrointestinal cancers. Tivozanib (AV-951) is a targeted anti-angiogenesis agent that has demonstrated acceptable tolerability in a phase I clinical trial. This study is designed to test the hypothesis that tivozanib (AV-951) can be combined with standard FOLFOX6 chemotherapy for the treatment of patients with colorectal and other gastrointestinal cancers. The purpose of this study is to determine the maximum dose of tivozanib (AV-951) that can be safely combined with FOLFOX6 chemotherapy, and to evaluate the safety profile, tolerability, and pharmacokinetics of this combination.
Read the detailed description
This is a Phase 1b, open-label, study design that will examine safety, tolerability, and maximum tolerated dose of tivozanib (AV-951) and FOLFOX6 in advanced colorectal cancer and other gastrointestinal cancers. In the study, only the doses of tivozanib (AV-951) will be escalated from 0.5 mg/day to 1.5 mg/day. All subjects will receive standard doses of FOLFOX6 chemotherapy every 2 weeks.
- Conditions
- Colorectal Cancer, Gastrointestinal Cancer
- Being tested
- Tivozanib (AV-951) plus FOLFOX6
- Keywords
- Advanced Colorectal Cancer and Other Gastrointestinal Cancers, tivozanib, AV-951
- Medical subject headings
- Colorectal Neoplasms, Gastrointestinal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tivozanib (AV-951) plus FOLFOX6Drug
Investigational product, dosage and mode of administration (1 cycle = 4 weeks of treatment):
Tivozanib (AV-951): 0.5 mg, 1.0 mg, and 1.5 mg oral once daily On Day -5 (± 2 days) subjects will receive a single dose of tivozanib (AV-951) for pharmacokinetic sampling. Beginning on Day 1 of Cycle 1, subjects will receive tivozanib (AV-951) once daily for 3 weeks followed by 1 week off. Tivozanib (AV-951) dosing repeats every cycle in the absence of disease progression or unacceptable toxicity. On days when both tivozanib (AV-951) and the FOLFOX6 chemotherapy regimen are co-administered, tivozanib (AV-951) will be administered immediately prior to the start of the FOLFOX6 chemotherapy regimen.
Subjects will receive FOLFOX6 chemotherapy every 2 weeks starting on Day 1 of Cycle 1. Subjects will receive 2 treatments of FOLFOX6 in each treatment cycle, starting on Day 1 and Day 15.
| Study group | Role | What they receive |
|---|---|---|
| single arm; multiple cohort | Experimental | Single arm; multiple cohort Receives: Drug: Tivozanib (AV-951) plus FOLFOX6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety, tolerability, and maximum tolerated dose of tivozanib (AV-951) in combination with FOLFOX6 chemotherapy.
Measured: • Minimum of 4 weeks for assessment of tolerability, minimum of 8 weeks (2 consecutive dosing cycles) for assessment of anti-tumor activity. Extended therapy may continue for up to 1 year from the subject's start of Cycle 1.
Secondary outcomes (1)
To characterize the pharmacokinetic profile of tivozanib (AV-951) and FOLFOX6 chemotherapy when administered together, and to assess the antineoplastic activity of the combination of tivozanib (AV-951) and FOLFOX6 chemotherapy.
Measured: • Minimum of 4 weeks for assessment of tolerability, minimum of 8 weeks (2 consecutive dosing cycles) for assessment of anti-tumor activity. Extended therapy may continue for up to 1 year from the subject's start of Cycle 1.
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 startJun 2008
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies 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
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- AVEO Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ferry Eskens, MD, PhD, Principal investigator, Erasmus Medical Center; Department of Medical OncologyE.G.E de Vries, Prof, MD, Principal investigator, University Medical Center GroningenJaroslow Jac, MD, Study director, AVEO Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00660153
- Sponsor's protocol ID
- AV-951-103
- Status last verified
- Aug 2012
- First submitted
- 15 Apr 2008
- Last updated
- 28 Aug 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Oldenhuis CN, Loos WJ, Esteves B, van Doorn L, Cotreau MM, Strahs AL, den Hollander MW, Gietema JA, de Vries EG, Eskens FA. A phase Ib study of the VEGF receptor tyrosine kinase inhibitor tivozanib and modified FOLFOX-6 in patients with advanced gastrointestinal malignancies. Clin Colorectal Cancer. 2015 Mar;14(1):18-24.e1. doi: 10.1016/j.clcc.2014.12.001. Epub 2014 Dec 16.
PubMed 25591799
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Open-Label, Dose-Escalation Study of Tivozanib (AV-951) Plus FOLFOX6 in Subjects With Advanced Colorectal Cancer and Other Gastrointestinal Cancers
- ClinicalTrials.gov ID
- NCT00660153
- Acronym / sponsor ID
- AV-951-103
- Conditions
- Colorectal Cancer, Gastrointestinal Cancer
- Keywords
- Advanced Colorectal Cancer and Other Gastrointestinal Cancers, tivozanib, AV-951
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- AVEO Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2008
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (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.
The FOLFOX6 regimen is a standard chemotherapy regimen for the treatment of patients with colorectal cancer and other gastrointestinal cancers. Tivozanib (AV-951) is a targeted anti-angiogenesis agent that has demonstrated acceptable tolerability in a phase I clinical trial. This study is designed to test the hypothesis that tivozanib (AV-951) can be combined with standard FOLFOX6 chemotherapy for the treatment of patients with colorectal and other gastrointestinal cancers. The purpose of this study is to determine the maximum dose of tivozanib (AV-951) that can be safely combined with FOLFOX6 chemotherapy, and to evaluate the safety profile, tolerability, and pharmacokinetics of this combination.
Detailed description
This is a Phase 1b, open-label, study design that will examine safety, tolerability, and maximum tolerated dose of tivozanib (AV-951) and FOLFOX6 in advanced colorectal cancer and other gastrointestinal cancers. In the study, only the doses of tivozanib (AV-951) will be escalated from 0.5 mg/day to 1.5 mg/day. All subjects will receive standard doses of FOLFOX6 chemotherapy every 2 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single arm; multiple cohort | Experimental | Drug: Tivozanib (AV-951) plus FOLFOX6Single arm; multiple cohort |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- ≥ 18-year-old males or females
- Histologically or cytologically confirmed metastatic colorectal cancer or other gastrointestinal malignancy for which FOLFOX6 chemotherapy is a standard treatment. Other gastrointestinal cancers include, but are not limited to, esophageal, gastric, and small intestine, appendiceal, and pancreatico-biliary cancers.
- Documented progressive disease
- Measurable or evaluable disease by RECIST. (Note: Subjects enrolled in the MTD Expansion Cohort are required to have measurable disease, according to RECIST.)
- No more than 2 prior chemotherapy regimens for metastatic disease (This does not include prior adjuvant chemotherapy with fluorouracil and/or oxaliplatin.)
Key exclusion criteria (38 listed)
- Primary CNS malignancies or clinically active CNS metastases
- Hematologic malignancies (includes leukemia in any form, lymphoma, and multiple myeloma)
- Any of the following hematologic abnormalities:
- Any of the following serum chemistry abnormalities:
- Significant cardiovascular disease, including:
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 |
|---|---|---|
| Tivozanib (AV-951) plus FOLFOX6Investigational product, dosage and mode of administration (1 cycle = 4 weeks of treatment): Tivozanib (AV-951): 0.5 mg, 1.0 mg, and 1.5 mg oral once daily On Day -5 (± 2 days) subjects will receive a single dose of tivozanib (AV-951) for pharmacokinetic sampling. Beginning on Day 1 of Cycle 1, subjects will receive tivozanib (AV-951) once daily for 3 weeks followed by 1 week off. Tivozanib (AV-951) dosing repeats every cycle in the absence of disease progression or unacceptable toxicity. On days when both tivozanib (AV-951) and the FOLFOX6 chemotherapy regimen are co-administered, tivozanib (AV-951) will be administered immediately prior to the start of the FOLFOX6 chemotherapy regimen. Subjects will receive FOLFOX6 chemotherapy every 2 weeks starting on Day 1 of Cycle 1. Subjects will receive 2 treatments of FOLFOX6 in each treatment cycle, starting on Day 1 and Day 15. | Drug | single arm; multiple cohort |
Primary outcome
To determine the safety, tolerability, and maximum tolerated dose of tivozanib (AV-951) in combination with FOLFOX6 chemotherapy.
Time frame: • Minimum of 4 weeks for assessment of tolerability, minimum of 8 weeks (2 consecutive dosing cycles) for assessment of anti-tumor activity. Extended therapy may continue for up to 1 year from the subject's start of Cycle 1.
1 secondary outcome
To characterize the pharmacokinetic profile of tivozanib (AV-951) and FOLFOX6 chemotherapy when administered together, and to assess the antineoplastic activity of the combination of tivozanib (AV-951) and FOLFOX6 chemotherapy.
Time frame: • Minimum of 4 weeks for assessment of tolerability, minimum of 8 weeks (2 consecutive dosing cycles) for assessment of anti-tumor activity. Extended therapy may continue for up to 1 year from the subject's start of Cycle 1.
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 28 Aug 2012.
- Derived from this study: PubMed 25591799Oldenhuis CN, Loos WJ, Esteves B, van Doorn L, Cotreau MM, Strahs AL, den Hollander MW, Gietema JA, de Vries EG, Eskens FA. A phase Ib study of the VEGF receptor tyrosine kinase inhibitor tivozanib and modified FOLFOX-6 in patients with advanced gastrointestinal malignancies. Clin Colorectal Cancer. 2015 Mar;14(1):18-24.e1. doi: 10.1016/j.clcc.2014.12.001. Epub 2014 Dec 16.
Related trials for Colorectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
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.
Ferry Eskens, MD, PhD principal investigator
Erasmus Medical Center; Department of Medical Oncology
E.G.E de Vries, Prof, MD principal investigator
University Medical Center Groningen
Jaroslow Jac, MD study director
AVEO Pharmaceuticals, Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tivozanib (AV-951) plus FOLFOX6 in people with Colorectal Cancer and Gastrointestinal Cancer, run by AVEO Pharmaceuticals, Inc. at 2 sites in Netherlands.
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 16 inclusion and 38 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 28 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. 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 determine the safety, tolerability, and maximum tolerated dose of tivozanib (AV-951) in combination with FOLFOX6 chemotherapy. (time frame: • Minimum of 4 weeks for assessment of tolerability, minimum of 8 weeks (2 consecutive dosing cycles) for assessment of anti-tumor activity. Extended therapy may continue for up to 1 year from the subject's start of Cycle 1.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00660153, which also lists 1 linked publication.
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 28 Aug 2012.