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Phase 2 Study With Abraxane (Nab®Paclitaxel) in Metastatic Colorectal Cancer

10 april 2020 bijgewerkt door: Celgene

A SINGLE ARM PHASE 2 STUDY TO EVALUATE THE SAFETY AND EFFICACY OF Nab®-PACLITAXEL, IN SUBJECTS WITH PREVIOUSLY TREATED METASTATIC COLORECTAL CANCER

The purpose of this study is to evaluate the safety and efficacy of Abraxane (nab-paclitaxel) in subjects with previously treated metastatic colorectal cancer. Subjects will be placed into two separate cohorts based on their RAS mutation status.

Studie Overzicht

Toestand

Voltooid

Interventie / Behandeling

Gedetailleerde beschrijving

ABI-007-COLO-001 is a Phase 2, single arm, open label, multicenter study to evaluate the efficacy and safety of Abraxane (nab-paclitaxel) given on days 1, 8 and 15 of a 28 day cycle in subjects with previously treated metastatic colorectal cancer. Subjects will be enrolled into cohorts by RAS mutation status (wildtype or mutated). Stage 1 in a given cohort will enroll 15 subjects in the Intention to Treat population and if more than 8 subjects have Progression Free Survival at the 8 week assessment, then Stage 2 will open in the respective cohort. Stage 2 will enroll an additional 28 subjects for a total of 43 subjects in each cohort. The study will be positive if more than 26 subjects with Progression Free Survival at the 8 week assessment are observed in 43 subjects per cohort. Interim analysis after Stage 1 did not meet protocol defined criteria to proceed to Stage 2. Patients currently enrolled will be followed for Progression Free Survival and until 28 days after last dose, secondary endpoints including overall survival will not be followed

Studietype

Ingrijpend

Inschrijving (Werkelijk)

41

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

      • Lille 59, Frankrijk, 59020
        • Centre Oscar Lambret, Dept. de Cancerologie Digestive et Urologique
      • Montpellier cedex 5, Frankrijk, 34298
        • Centre Regional de Lutte contre le Cancer Val d'Aurelle
      • Saint Herblain 44, Frankrijk, 44805
        • CRLCC Centre Rene Gauducheau
      • Saint-Cloud, Frankrijk, 92210
        • Institut Curie
      • Vandoeuvre-Les-Nancy, Frankrijk, 54511
        • Centre Alexis Vautrin
      • Villejuif, Frankrijk, 94805
        • Institut Gustave Roussy Hematologie

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria: - 1. Subject is ≥ 18 years old at the time of signing the Informed Consent Form 2. Subject has histological or cytological diagnosis of adenocarcinoma of the colon or rectum, with evidence of metastasis 3. Subject has a known KRAS mutation status (mutated or wild-type). NRAS mutation status may be unknown. 4. Subject has documented disease progression ≤ 2 months after the last administration of the last standard therapy. a. Subjects treated with oxaliplatin in the adjuvant setting, should have progressed during or within 6 months of completion of adjuvant therapy 5. Subject has either received prior treatment or was not a candidate for prior treatment, with fluoropyrimidine, oxaliplatin, irinotecan and an anti-VEGF therapy (e.g. bevacizumab or ziv-aflibercept); and if RAS wild-type tumors, an anti-EGFR therapy (e.g. cetuximab or panitumumab). 6. Subject has Eastern Cooperative Oncology Group performance status 0 or 1 7. Subject has radiographically-documented measurable disease, as per Response Evaluation Criteria in Solid Tumors version 1.1 criteria 8. Subject has adequate organ functions, evidenced by the following: a. Aspartate Aminotransferase (SGOT), Alanine Transaminase (SGPT) ≤ 2.5 × upper limit of normal range, or < 5 x upper limit of normal range if liver metastasis present b. Total bilirubin ≤ 1.5 × upper limit of normal range c. Creatinine ≤ 1.5 × upper limit of normal range 9. Subject has adequate bone marrow function, evidenced by the following: a. Absolute neutrophil count ≥ 1.5 × 109 cells/millimeters3 b. Platelets ≥ 100 × 109 cells/millimeters3 (transfusion independent, defined as not receiving platelet transfusions within 7 days prior to laboratory sample) c. Hemoglobin ≥ 9 grams/decilitre (transfusion is permitted to fulfill this criterion) 10. Females of child-bearing potential (defined as a sexually mature woman who (1) has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or (2) has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time during the preceding 24 consecutive months]) must: a. Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis), or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting Investigational Product therapy (including dose interruptions), and for 3 months following the last dose of Investigational Product; and b. Have a negative serum pregnancy test (β -human Chorionic Gonadotrophin) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy. This applies even if the subject practices true abstinence* from heterosexual contact. * True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Note: Periodic abstinence (e.g, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. 11. Male subjects must practice true abstinence* or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following Investigational Product discontinuation, even if he has undergone a successful vasectomy. 12. Subject must understand and voluntarily sign an Informed Consent Form prior to any study related assessments or procedures being conducted. 13. Subject must be able to adhere to the study visit schedule and other protocol requirements. Exclusion Criteria: - 1. Subject has current or a history of brain metastasis. In subjects who are symptomatic, a brain scan is required to exclude metastasis. 2. Subject has ≥ National Cancer Institute Common Terminology Criteria for Adverse Events grade 2 peripheral neuropathy at screening 3. Subject has had prior treatment with regorafenib 4. Subject has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting Investigational Product, and/or from whom ≥ 30% of the bone marrow was irradiated. Radiation therapy to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed. 5. Subject has had major surgery within 14 days prior to starting Investigational Product or has not recovered from postoperative complications 6. Subject has not recovered from the acute toxic effects of prior anticancer therapy, radiation or major /significant trauma 7. Subject has a history of allergy or hypersensitivity to nab-paclitaxel or any of the excipients 8. Subject has a known history of the following within 6 months prior to enrollment (the decision to include the subject in the study): a myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or Electrocardiogram abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder 9. Subject has a known infection with hepatitis B or C, or history of human immunodeficiency virus infection, or subject receiving immunosuppressive or myelosuppressive medications that would in the opinion of the investigator, increase the risk of serious neutropenic complications 10. Subject has an active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment 11. Subject has any other malignancy within 5 years prior to enrolment, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, or non-melanomatous skin cancer (all treatment of which should have been completed 6 months prior to enrollment) 12. Subject has a history of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa) 13. Subject has a history of interstitial lung disease , history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies 14. Subject has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate subject participation in the clinical study (e.g. chronic pancreatitis, chronic active hepatitis, etc.) 15. Subject is enrolled in any other clinical protocol or investigational study with an interventional agent or assessments that may interfere with study procedures 16. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study 17. Subject has any condition that confounds the ability to interpret data from the study 18. Subject is unwilling or unable to comply with study procedures 19. Subject is a pregnant or nursing female

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Abraxane (nab®paclitaxel)
Abraxane (nab®paclitaxel) 125 milligrams per meter squared on days 1, 8 and 15 of a 28 day cycle
Andere namen:
  • Abraxane (nab®paclitaxel)

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Progression Free Survival (PFS) Rate as Measured at Week 8
Tijdsspanne: At week 8 assessment period; up to 56 days
PFS rate was measured by Investigator Assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 from the start of study treatment to disease progression or death from any cause, whichever occurred first.
At week 8 assessment period; up to 56 days

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Percentage of Participants With Stable Disease for ≥ 8 Weeks, or Complete or Partial Response According to RECIST Version 1.1; Disease Control Rate (DCR)
Tijdsspanne: At week 8 and later; up to day 241
DCR was defined as the combined incidence of stable disease confirmed CR or PR and stable disease (SD) measured at the Week 8 assessment or later.
At week 8 and later; up to day 241
Overall Survival
Tijdsspanne: Up to 241 days
Overall Survival was the time from the first dose of study drug to patient death from any cause.
Up to 241 days
Overall Response Rate (ORR)
Tijdsspanne: Up to 241 days
ORR was defined as the combined incidence of Complete Response (CR) and Partial Response (PR), confirmed no less than 4 weeks after the criteria for response were first met based on RECIST 1.1. Tumor responses were assessed every 2 cycles using RECIST 1.1 and defined as: • Complete response-disappearance of all target lesions • Partial response- At least a 30% decrease in the sum of diameters of target lesions from baseline • Stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD) • Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.
Up to 241 days
Duration of Response (DOR)
Tijdsspanne: Up to 241 days
Duration of response was defined as the time from the first tumor assessment when the confirmed CR/PR response criterion was met to the date of disease progression based on investigational assessment following RECIST 1.1.
Up to 241 days
Number of Participants With Adverse Events
Tijdsspanne: Time of the first dose of study treatment to 28 days after the last dose of study drug; maximum treatment duration was 24 weeks
A treatment emergent adverse events (TEAE) was defined as any AE occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. A TESAE is defined as any serious adverse event (SAE) occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. Safety and Severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0; Severity of AEs were graded (including second primary malignancies) as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Lifethreatening; Grade 5-Fatal;
Time of the first dose of study treatment to 28 days after the last dose of study drug; maximum treatment duration was 24 weeks

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Kaplan Meier Estimate of PFS by Investigator Assessment
Tijdsspanne: Up to 241 days
PFS was measured as time from the date of first dose to the date of disease progression according to RECIST 1.1 or death from any cause, whichever was earlier.
Up to 241 days

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Publicaties en nuttige links

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Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

5 mei 2014

Primaire voltooiing (Werkelijk)

10 november 2014

Studie voltooiing (Werkelijk)

9 januari 2015

Studieregistratiedata

Eerst ingediend

31 maart 2014

Eerst ingediend dat voldeed aan de QC-criteria

31 maart 2014

Eerst geplaatst (Schatting)

3 april 2014

Updates van studierecords

Laatste update geplaatst (Werkelijk)

21 april 2020

Laatste update ingediend die voldeed aan QC-criteria

10 april 2020

Laatst geverifieerd

1 april 2020

Meer informatie

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Klinische onderzoeken op ABI-007

3
Abonneren