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Colorectal Cancer MetastaticPhase 1/2AMORNCT01955629

Study of Aflibercept as Maintenance Therapy Following Induction With Aflibercept in Combination With XELOX, as First-Line Treatment for Metastatic Colorectal Cancer Patient

A Phase 1/2 study testing Aflibercept AVE0005, Oxaliplatin and Capecitabine in people with Colorectal Cancer Metastatic, run by Sanofi at 2 sites in Italy.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Primary Objectives: Study Part 1: To determine the recommended dose for the aflibercept, oxaliplatin and capecitabine (XELOX) combination to be used in the Part 2 of the study. Study Part 2: To assess the percentage of participants without progression of the disease at 6 months after the start of maintenance therapy… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer Metastatic
What is being tested?
Aflibercept AVE0005, Oxaliplatin and Capecitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
2 sitesItaly
Study dates
Dec 2013to Mar 2015
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically or cytologically-proven adenocarcinoma of the colon or rectum.
  • Metastatic disease not amenable to potentially curative treatment (i.e. unresectable).
  • Measurable lesion as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
  • No prior systemic anti-cancer treatment for metastatic disease.
  • No prior adjuvant treatment after resection of distant metastases.
  • No prior treatment with angiogenesis inhibitors.

Who cannot join

  • Age <18 years.
  • Eastern Cooperative Oncology Group Performance status >/= 2.
  • Less than 4 weeks from prior radiotherapy or prior surgery (or until the surgical wound is fully healed).
  • Treatment with any other investigational product within the prior 28 days.
  • Other prior neoplasm.
  • History of brain metastases, active seizure disorder, uncontrolled spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
Show all 24Show fewer
  • Any of the following within the prior 6 months: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, severe congestive heart failure, stroke or transient ischemic attack.
  • Any of the following within the prior 3 months: moderate/severe gastrointestinal bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event.
  • Deep vein thrombosis within the prior 4 weeks.
  • Any severe acute or chronic medical condition, which could impair the ability of the participant to participate in the study.
  • Inadequate bone marrow, liver and renal function: neutrophils < 1.5x10^9/L, platelets < 100x10^9/L, hemoglobin < 9.0 g/dL, total bilirubin >1.5 x upper normal limit (ULN), transaminases >3 x ULN (unless liver metastasis are present), alkaline phosphatase >3 x ULN (unless liver metastasis are present), serum creatinine > 1.5 x ULN.
  • Participants on anticoagulant therapy with warfarin.
  • Symptomatic peripheral sensory neuropathy.
  • Inability to take oral medications.
  • Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea, malabsorption syndrome, unresolved bowel obstruction/sub-obstruction, surgery more extensive than hemicolectomy, extensive small intestine resection with chronic diarrhea.
  • Known dihydropyrimidine dehydrogenase deficiency.
  • known history of hypersensitivity to aflibercept.
  • Any contraindication to administer oxaliplatin or capecitabine as per package insert of each drug.
  • Urine protein-creatinine ratio (UPCR) >1 on morning spot urinalysis or proteinuria > 500 mg/24-h.
  • Uncontrolled hypertension within the prior 3 months.
  • Evidence of clinically significant bleeding predisposition or underlying coagulopathy, non-healing wound.
  • Pregnant or breast-feeding women.
  • Participants with reproductive potential who do not agree to use an accepted effective method of contraception.
  • The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial locations and contacts

2 sites in 1 country.

Italy2 sites

  • Investigational Site Number 380-001

    Genova, 16132

  • Investigational Site Number 380-002

    Milan

Other trials in Italy

About this study

Official title: A Single-Arm, Open Label Study of Aflibercept as Maintenance Therapy Following Induction With Aflibercept in Combination With XELOX, as First-Line Treatment for Metastatic Colorectal Cancer Patient

Primary Objectives:

Study Part 1: To determine the recommended dose for the aflibercept, oxaliplatin and capecitabine (XELOX) combination to be used in the Part 2 of the study.

Read more

Study Part 2: To assess the percentage of participants without progression of the disease at 6 months after the start of maintenance therapy with aflibercept single-agent, following the first-line induction therapy with XELOX and aflibercept combination in participants with previously untreated metastatic colorectal cancer.

Secondary Objective:

Study Part 2: Include the evaluation of progression free survival, overall survival, response to treatment, the overall safety (during induction and maintenance therapy) and the assessment of aflibercept pharmacodynamics and biomarkers parameters.

Read the detailed description

The duration of the study for each participant includes a period for screening of up to 3 weeks, study drug administrations every 3 weeks up to disease progression, unacceptable toxicity or participant's refusal of further study treatment, followed by a minimum of 30-day follow-up after the last study treatment administration.

After study treatment discontinuation each participant will be followed-up until death, participant's refusal or end of study (whichever comes first).

This trial is being conducted in Europe, where the INN designation for the study molecule is "aflibercept" and this term is therefore used throughout the synopsis. In the US, the US proper name is "ziv-aflibercept".

Being tested
Aflibercept AVE0005, Oxaliplatin, Capecitabine

What participants receive

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

  • Aflibercept AVE0005Drug

    Also called Zaltrap

    Pharmaceutical form: Concentrate for solution for infusion; Route of administration: Intravenous

  • OxaliplatinDrug

    Also called Eloxatin, SR96669

    Pharmaceutical form: Concentrate for solution for infusion; Route of administration: Intravenous

  • CapecitabineDrug

    Pharmaceutical form: Tablets; Route of administration: Oral

Study groups in NCT01955629
Study groupRoleWhat they receive
Aflibercept + XELOX (Oxaliplatin and Capecitabine)ExperimentalAflibercept 6 mg/kg every 3 weeks (q3w) in combination with Oxaliplatin 100 mg/m^2 q3w and Capecitabine 850 mg/m^2 twice daily orally (from Day 1 to Day 14 of each cycle), up to 6 cycles as induction therapy, followed by aflibercept 6 mg/kg q3w as maintenance therapy up to disease progression or unacceptable toxicity or participant's refusal of further treatment.
Receives: Drug: Aflibercept AVE0005; Drug: Oxaliplatin; Drug: Capecitabine

What is being measured

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

  1. Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)

    DLTs were assessed using the national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) version 4.03. DLTs were defined as any of following AEs: grade 4 neutropenia lasting >7 consecutive days; febrile neutropenia or neutropenic infection; grade 4 thrombocytopenia; grade 3 thrombocytopenia associated with bleeding requiring transfusion; grade 4 non-hematological treatment related event; grade 3 nausea/vomiting or diarrhea lasting >/= 4 days despite corrective measures; grade 3 other non-hematological toxicities: anorexia, fatigue, hypertension only if G4 or not medically controlled and G3 peripheral sensory neuropathy that did not improve to G<2 at time of retreatment; urinary protein excretion of >3.5 gram per 24 hours that did not recover to <2.0 gram per 24 hours within 2 weeks; symptomatic arterial thromboembolic events including cerebrovascular accidents, myocardial infarction, transient ischemic attacks, new onset or worsening of pre-existing angina.

    Measured: Cycle 1 (Up to 3 weeks)

  2. Part 2: Number of Participants With Progression Free Survival (PFS) at 6 Months After the Start of Maintenance Therapy

    It describes the number of participants alive without progression at 6 months after the start of Aflibercept maintenance therapy.

    Measured: 6 months after the start of maintenance therapy.

Secondary outcomes (7)

  1. Part 1: Number of Participants With Tumor Responses (Complete Response [CR], Partial Response [PR], Stable Disease [SD] or Progressive Disease [PD])

    Tumor assessment was performed by abdomino-pelvic computed tomography scan or magnetic resonance imaging (MRI) and chest X-ray or chest CT-scan to assess the disease status at baseline and then every 9 weeks during study treatment up to DP. Target lesions were evaluated using response evaluation criteria in solid tumors (RECIST) version 1.1, wherein CR = disappearance of all target lesions; PR = 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD; PD =20% increase in the sum of the LD of target lesions taking as reference the smallest sum in the study and SD = small changes that did not meet above criteria.

    Measured: Baseline and every 9 weeks up to DP (up to 15 months).

  2. Part 2: Progression Free Survival (PFS)

    PFS was defined as the time interval from the date of registration into the study to the date of first observation of DP or death (due to any cause), whichever was first.

    Measured: From the date of enrollment up to the date of DP or death, whichever occurred first (up to 15 months).

  3. Part 2: Overall Survival (OS)

    OS was defined as the time interval from the date of registration into the study to the date of death due to any cause. In the absence of confirmation of death, survival time was to be censored at the earliest between the last date the participant was known to be alive and the end of study date.

    Measured: From the date of enrollment up to the date of death (up to 15 months).

  4. Part 2: Overall Rate of Resectability of Metastatic Lesions

    Overall metastases resection rate was defined as the percentage of participants reaching an R0 metastases resection, defined as the complete absence of invasive carcinoma on histological examination at the time of definitive surgery.

    Measured: 12 months after the last participant enrolled.

  5. Part 2: Number of Participants With CR or PR

    Tumor assessment was performed by abdomino-pelvic computed tomography scan or MRI and chest X-ray or chest CT-scan to assess the disease status at baseline and then every 9 weeks during study treatment up to DP. Target lesions were evaluated using RECIST version 1.1, wherein CR = disappearance of all target lesions; PR = 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.

    Measured: Baseline and every 9 weeks up to end of study completion (15 months).

  6. Part 2: Pharmacodynamic Parameters: Modulation of Circulating Analytes

    Blood and tumor samples were to be collected to evaluate the pharmacodynamic parameters including the assessment of the modulation of circulating analytes such as cytokines and angiogenic factors.

    Measured: Baseline (within 21 days before registration); Day 1/pre-dose of Cycle 1, 2 and 3 of induction phase and maintenance phase; 30 ± 3 days after the last aflibercept administration.

  7. Part 2: Aflibercept Biomarkers Evaluation

    Blood and tumor samples were to be collected to evaluate proteomic biomarkers such as factors and receptors related to angiogenesis process, inflammation, and tumor progression.

    Measured: Baseline (within 21 days before registration); Day 1/pre-dose of Cycle 1, 2 and 3 of induction phase and maintenance phase; 30 ± 3 days after the last aflibercept administration.

Timeline

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

  1. First posted7 Oct 2013 (estimated)
  2. Study startDec 2013
  3. Primary completionMar 2015
  4. Study completionMar 2015

Why it stopped: The study enrollment was prematurely halted due to safety reasons.

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01955629
Sponsor's protocol ID
AFLIBC06561
Other IDs
2013-000858-22, U1111-1143-3015
Acronym
AMOR
Status last verified
Mar 2016
First submitted
13 Sep 2013
Last updated
18 Apr 2016
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Aflibercept AVE0005, Oxaliplatin and Capecitabine in people with Colorectal Cancer Metastatic, run by Sanofi at 2 sites in Italy.

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 6 inclusion and 24 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: stopped early, as of the sponsor's last update on 18 Apr 2016. 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 Italy. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: Cycle 1 (Up to 3 weeks)). The study lists 2 primary outcomes in all. 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 NCT01955629.

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 18 Apr 2016.

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