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

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ClinicalTrials.gov Identifier: NCT01843725
Recruitment Status : Completed
First Posted : May 1, 2013
Last Update Posted : January 31, 2018
Sponsor:
Information provided by (Responsible Party):
Jules Bordet Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancers Metastatic Gastric Cancers Metastatic Oesophageal Cancers Metastatic Pancreatic Cancers Metastatic Biliary Cancers Metastatic Breast Cancers Drug: capecitabine Drug: aflibercept Drug: Capecitabine Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Modulation of Metabolic Index in Tailoring Treatment of Incurable Metastatic ColoRectal Cancer (CRC) Program 1.
Study Start Date : September 2013
Actual Primary Completion Date : October 2016
Actual Study Completion Date : October 2016


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 Name: Xeloda

Drug: aflibercept
Intravenous 6mg/kg every 3 weeks
Other Name: 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 Name: Zaltrap

Drug: Capecitabine
dose escalation, from 1700 to 2500mg/m2/day 2 weeks out of 3
Other Name: Xeloda




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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) ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01843725


Locations
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Belgium
Institut Jules Bordet
Brussels, Belgium, 1000
Sponsors and Collaborators
Jules Bordet Institute
Investigators
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Principal Investigator: Alain Hendlisz, MD Jules Bordet Institute

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Responsible Party: Jules Bordet Institute
ClinicalTrials.gov Identifier: NCT01843725     History of Changes
Other Study ID Numbers: Mom1-AD12
2012-005169-11 ( EudraCT Number )
First Posted: May 1, 2013    Key Record Dates
Last Update Posted: January 31, 2018
Last Verified: August 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jules Bordet Institute:
breast cancer
digestive cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Colorectal Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents