Phase 1 Study Testing the Combination of Aflibercept and Capecitabine in Metastatic Digestive and Breast Cancers (MOMENTUM1)

January 29, 2018 updated by: Jules Bordet Institute

Modulation of Metabolic Index in Tailoring Treatment of Incurable Metastatic ColoRectal Cancer (CRC) Program 1.

Prospective non randomized, non-comparative, dose escalation, two arms open phase I trial to assess the safety and tolerability of capecitabine given in combination with aflibercept in patients with measurable or evaluable, chemorefractory digestive tumors or breast tumors in terms of the Maximum Tolerated Dose (MTD) and the Dose-Limiting Toxicities (DLTs), To establish the Recommended Phase II Dose (RP2D) of capecitabine in combination with Aflibercept.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Aflibercept has been found to be active with a broad pharmacological index against early and advanced stage disease in a variety of preclinical solid tumor models including sarcomas, and ovarian, prostate, mammary, colon, and gastric carcinomas either as a single agent or in combination with cytotoxic agents.

Metronomic chemotherapy, namely administration of continuous low-dose chemotherapy at close, regular intervals, with no prolonged drug-free interruptions, bases its rationale on the fact that virtually all classes of cancer chemotherapeutic drugs are designed to damage DNA or disrupt microtubules of dividing cells. Endothelial cell division takes place during new blood vessel formation, including tumour angiogenesis. Frequent administration of most cytotoxic agents at low doses is thought to increase their putative antiangiogenic activity.

This strategy lowers the toxicity and theoretically the risk of emergence of drug-resistant tumour cells compared to classic maximum tolerated dose (MTD)-based chemotherapy.

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1000
        • Institut Jules Bordet

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed digestive or breast cancer that is metastatic or unresectable, for which no curative measures are possible, and chemorefractory to all known medications in the respective fields.
  • Age ≥ 18 years.
  • Life expectancy of greater than 12 weeks.
  • ECOG (Eastern Cooperative Oncology Group) performance status ≤ 1.

  • Normal organ and marrow function as defined below:

    • Leukocytes > 3,000/microLiter (mcL)
    • Hb>10g/mcL
    • Absolute neutrophil count > 1,500/mcL
    • Platelets > 100,000/mcL
    • Total bilirubin within 2 × institutional upper limit of normal
    • AST (aspartate amino transferase)/ALT (alanine amino transferase)/ALKP (Alkaline Phosphatase) levels < 5 × institutional upper limit of normal for liver metastases, < 2.5 ULN (Upper Limit of Normal) in case of no liver metastases
    • Creatinine within 2 × institutional upper limit of normal or creatinine clearance > 35 mL/min
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Signed written informed consent (approved by an Independent Ethics Committee (IEC)) obtained prior to any study specific baseline procedures.

Exclusion Criteria:

  • Patients with malabsorption or dysfunctional GI tract.
  • Participants who have had chemotherapy or radiotherapy (except limited radiotherapy for bone metastasis for instance) within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  • Participants should not receive any other experimental agents.

  • Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

    • History of cardiovascular ischemic disease or cerebrovascular incident within the last six months, NYHA class III and IV congestive heart failure.
    • Intolerance to atropine sulfate or loperamide
    • Known dihydropyrimidine dehydrogenase deficiency
    • Treatment with CYP3A4 inducers unless discontinued > 7 days prior to randomization
    • Any of the following in 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis.
  • Major surgery within 6 weeks.
  • Uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women, lactation or refusal to use adequate contraceptive measures (hormonal or barrier method of birth control, abstinence).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Metronomic arm
capecitabine 1100 to 1600 mg/m2/day orally in association with aflibercept 6mg/kg intravenous every 3 weeks
Drug: capecitabine
escalation dose of capecitabine continuously
Other Names:
  • Xeloda
Drug: aflibercept
Intravenous 6mg/kg every 3 weeks
Other Names:
  • Zaltrap
Experimental: Intermittent arm
capecitabine 1700 to 2500 mg/m2/day orally 2 weeks out of 3 and aflibercept 6mg/kg intravenous every 3 weeks
Drug: aflibercept
Intravenous 6mg/kg every 3 weeks
Other Names:
  • Zaltrap
Drug: Capecitabine
dose escalation, from 1700 to 2500mg/m2/day 2 weeks out of 3
Other Names:
  • Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine the maximum tolerated dose and the recommended phase II dose of capecitabine in association with aflibercept
Time Frame: The time point of the first toxicity evaluation would be the end of the first cycle (3 weeks)
To assess the safety and tolerability of capecitabine given in combination with aflibercept in patients with measurable or evaluable, chemorefractory digestive tumors or breast tumors in terms of the Maximum Tolerated Dose (MTD), the Dose-Limiting Toxicities (DLTs), and to determine the Recommended Phase II Dose (RP2D) of capecitabine in combination with aflibercept.
The time point of the first toxicity evaluation would be the end of the first cycle (3 weeks)

Secondary Outcome Measures

Outcome Measure
Time Frame
The secondary endpoint is preliminary data on efficacy, and this will be evaluated using CT scan or MRI using RECIST (Response Evaluation Criteria in Solid Tumors) v1.1
Time Frame: after 2 cycles (6 weeks)
after 2 cycles (6 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jules Bordet Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Actual)

October 1, 2016

Study Completion (Actual)

October 1, 2016

Study Registration Dates

First Submitted

April 25, 2013

First Submitted That Met QC Criteria

April 30, 2013

First Posted (Estimate)

May 1, 2013

Study Record Updates

Last Update Posted (Actual)

January 31, 2018

Last Update Submitted That Met QC Criteria

January 29, 2018

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Mom1-AD12
  • 2012-005169-11 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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