AzTrials
AzTrials

Carcinoma, Renal CellPhase 1NCT01441388

A Study Of Crizotinib Plus VEGF Inhibitor Combinations In Patients With Advanced Solid Tumors.

A Phase 1 study testing Crizotinib plus VEGF inhibitor combinations, Crizotinib plus axitinib and Crizotinib plus sunitinib in people with Carcinoma, Renal Cell and Glioblastoma, run by Pfizer.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

Despite the success of anti-angiogenic therapy in multiple treatment settings, a fraction of patients are refractory to vascular endothelial growth factor (VEGF) inhibitor treatment while the majority of patients will eventually develop evasive resistance and exhibit disease progression while on therapy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Crizotinib plus VEGF inhibitor combinations, Crizotinib plus axitinib and Crizotinib plus sunitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Dec 2011to Nov 2013
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

  • Dose Escalation Population: Histological or cytological diagnosis of advanced/metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available. Lesions may be measurable or non measurable.
  • Expansion Population 1: Patients with histologically confirmed metastatic renal cell cancer with no prior systemic therapy directed at the malignant tumor.
  • Expansion Population 2: Patients with histologically confirmed metastatic renal cell cancer whose prior systemic therapy directed at the malignant tumor was single agent VEGF inhibitor and who now have acquired resistance to this treatment. Resistance is defined as progression following an initial response (complete or partial), or stable disease for at least 6 months on single agent VEGF inhibitor.
  • Expansion Population 3: Patients with histologically confirmed glioblastoma whose disease has failed on previous therapy, and which must have included treatment with external beam radiation and temozolomide chemotherapy, and who now have radiographically recurrent or progressive disease.
  • Expansion Population 4: Patients with histologically confirmed advanced-stage (unresectable or metastatic) hepatocellular carcinoma who have not received previous systemic therapy directed at the malignant tumor will be eligible to receive crizotinib plus sorafenib, should this combination be tested. Eligibility criteria also include normal hepatic function or Child-Pugh hepatic function class A.

Who cannot join

  • Patients with hemorrhagic brain metastases or with known symptomatic brain metastases requiring steroids.
  • Major surgery within 4 weeks of starting study treatment.
  • Radiation therapy within 2 weeks of starting study treatment.
  • Hypertension that cannot be controlled with medications (>150/90 mmHg despite optimal medical therapy).
  • For glioblastoma patients: Prior treatment of glioblastoma with Gliadel wafers, stereotactic radiation, or brachytherapy unless there is pathological or definitive radiological evidence (PET scan or perfusion MRI) of recurrent tumor or unless there is new enhancement outside of the radiation field. History of Grade 2 or greater acute intracranial hemorrhage. Radiation therapy (RT) for glioblastoma within 3 months unless there is either: a) histopathologic confirmation of recurrent tumor, or b) new enhancement on MRI outside of the RT treatment field.Concomitant treatment with therapeutic doses of anticoagulants (low dose warfarin (Coumadin) up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed).

About this study

Official title: A Phase 1B, Open-Label, Dose Escalation Study To Evaluate Safety, Pharmacokinetics And Pharmacodynamics Of Crizotinib (PF-02341066) Plus VEGF Inhibitor Combinations In Patients With Advanced Solid Tumors.

Despite the success of anti-angiogenic therapy in multiple treatment settings, a fraction of patients are refractory to vascular endothelial growth factor (VEGF) inhibitor treatment while the majority of patients will eventually develop evasive resistance and exhibit disease progression while on therapy. It is proposed that mesenchymal-epithelial transition factor (c-MET) and its ligand hepatocyte growth factor (HGF or scatter factor) contribute significantly to VEGF inhibitor resistance such that combining a c-MET inhibitor with a VEGF inhibitor will provide additional clinical activity compared to VEGF inhibitor alone. This hypothesis will be tested using the cMET/ALK inhibitor, crizotinib, in combination with individual VEGF inhibitors. Three combinations will be prioritized, namely crizotinib plus axitinib, crizotinib plus sunitinib and crizotinib plus bevacizumab, with a fourth combination, crizotinib plus sorafenib to be tested only if crizotinib does not combine with either axitinib and/or sunitinib.

Being tested
Crizotinib plus VEGF inhibitor combinations, Crizotinib plus axitinib, Crizotinib plus sunitinib, Crizotinib plus bevacizumab, Crizotinib plus sorafenib
Keywords
Phase 1b, crizotinib, sunitinib, axitinib, sorafenib, bevacizumab, cMET inhibitor, VEGF inhibitor, crizotinib combination
Medical subject headings
Carcinoma, Renal Cell, Glioblastoma, Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Crizotinib plus VEGF inhibitor combinationsDrug

    Three combinations will be prioritized, namely crizotinib plus axitinib, crizotinib plus sunitinib and crizotinib plus bevacizumab, with a fourth combination, crizotinib plus sorafenib to be tested only if crizotinib does not combine with either axitinib and/or sunitinib. All study drugs are tablets or capsules except for bevacizumab which is parenteral (intravenous). Dosage, frequency and duration to be determined.

  • Crizotinib plus axitinibDrug

    Study drugs are tablets or capsules; dosage, frequency and duration to be determined.

  • Crizotinib plus sunitinibDrug

    Study drugs are tablets or capsules; dosage, frequency and duration to be determined.

  • Crizotinib plus axitinibDrug

    Study drugs are tablets or capsules; dosage, frequency and duration to be determined.

  • Crizotinib plus sunitinibDrug

    Study drugs are tablets or capsules; dosage, frequency and duration to be determined.

  • Crizotinib plus bevacizumabDrug

    Study drugs are tablets or capsules except for bevacizumab which is parenteral (intravenous). Dosage, frequency and duration to be determined.

  • Crizotinib plus sorafenibDrug

    Study drugs are tablets or capsules; dosage, frequency and duration to be determined.

Study groups in NCT01441388
Study groupRoleWhat they receive
Dose EscalationExperimentalHistological or cytological diagnosis of advanced/metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available.
Receives: Drug: Crizotinib plus VEGF inhibitor combinations
Expansion Population 1ExperimentalPatients with histologically confirmed metastatic renal cell cancer with no prior systemic therapy directed at the malignant tumor.
Receives: Drug: Crizotinib plus axitinib; Drug: Crizotinib plus sunitinib
Expansion Population 2ExperimentalPatients with histologically confirmed metastatic renal cell cancer whose prior systemic therapy directed at the malignant tumor was single agent VEGF inhibitor and who now have acquired resistance to this treatment.
Receives: Drug: Crizotinib plus axitinib; Drug: Crizotinib plus sunitinib
Expansion Population 3ExperimentalPatients with histologically confirmed glioblastoma whose disease has failed on previous therapy, and which must have included treatment with external beam radiation and temozolomide chemotherapy, and who now have radiographically recurrent or progressive disease.
Receives: Drug: Crizotinib plus bevacizumab
Expansion Population 4ExperimentalPatients with histologically confirmed advanced-stage (unresectable or metastatic) hepatocellular carcinoma who have not received previous systemic therapy directed at the malignant tumor will be eligible to receive crizotinib plus sorafenib, should this combination be tested.
Receives: Drug: Crizotinib plus sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicities (DLTs).

    Measured: 12 months

Secondary outcomes (9)

  1. Duration of Response (DR)

    Measured: 24 months

  2. Progression free survival (PFS)

    Measured: 24 months

  3. Area under the plasma concentration versus time curve (AUC) of crizotinib and each VEGF inhibitor

    Measured: 24 months

  4. Best overall response, as assessed using the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 or , in the case of GBM (glioblastoma multiforme , RANO (Response Assessment in Neuro-Oncology) criteria.

    Measured: 24 months

  5. Overall survival (OS) up to 12 months

    Measured: 24 months

  6. Pre- and post-dose levels of soluble peripheral blood biomarkers.

    Measured: 24 months

  7. Tumor tissue biomarkers.

    Measured: 18 months

  8. 6-month progression free survival proportion (PFS6) for glioblastoma patients

    Measured: 24 months

  9. Peak plasma concentration (Cmax) of crizotinib and each VEGF inhibitor

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2011 (estimated)
  2. Study startDec 2011
  3. Primary completionNov 2013 (estimated)
  4. Study completionNov 2013 (estimated)

Why it stopped: Business/Operational issues

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01441388
Sponsor's protocol ID
A8081030
Status last verified
Dec 2011
First submitted
23 Sep 2011
Last updated
20 Dec 2011
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Crizotinib plus VEGF inhibitor combinations, Crizotinib plus axitinib and Crizotinib plus sunitinib in people with Carcinoma, Renal Cell and Glioblastoma, run by Pfizer.

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 5 inclusion and 5 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: withdrawn, as of the sponsor's last update on 20 Dec 2011. Status can change between updates, so confirm with the study contact before making plans.

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 was withdrawn before enrolling participants, so there are no results.

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?

Dose Limiting Toxicities (DLTs). (time frame: 12 months). 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 NCT01441388.

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 20 Dec 2011.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in