Back to resultsMEN1309 I.v. Infusion in Pts With CD205-positive Metastatic Solid Tumors and Relapsed or Refractory NHL Ph I Study (CD205SHUTTLE)
Primary Purpose
Metastatic Solid Tumors, Relapsed/Refractory Non-Hodgkin Lymphoma
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
MEN1309
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Solid Tumors focused on measuring Solid Tumors, Non-Hodgkin Lymphoma, NHL, MEN1309, CD205, Relapsed, Refractory, R-R NHL, ADC, Antibody-Drug Coniugate, Metastatic Tumors
Eligibility Criteria
Main Inclusion Criteria:
- Male or female patients aged ≥ 18 years.
Patients with:
- confirmed diagnosis of advanced or metastatic solid tumor and diagnosis of multiple relapsed or refractory NHL;
- progressive after last treatment received;
- availability of archived tumor material, either as a block or slides;
- measurable or evaluable disease by Response Evaluation Criteria in solid tumors guideline (RECIST v1.1) and by Cheson Criteria (The Lugano Classification, 2014) in NHL.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.
- Neutrophil count ≥ 1,500/µL; platelets ≥ 100,000/µL; haemoglobin ≥ 9 g/dL.
- Adequate renal and hepatic laboratory assessments.
- Life expectancy of at least 2 months.
- Woman of childbearing potential (WOCBP) who agrees to use highly effective contraception (see Appendix I).
Main Exclusion Criteria:
- Central nervous system involvement (excluding treated stable cerebral metastasis, not requiring therapy to control symptoms in the last 60 days).
- Pregnant or breastfeeding women.
- Life-threatening illnesses other than solid tumors and NHL, uncontrolled medical conditions or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or put the study outcomes at risk.
- Less than 2 previous cancer treatments, including high dose chemotherapy and ASCT, for NHL unless patient refuses standard therapy and/or is not eligible for ASCT.
- Have significant, uncontrolled, or active cardiovascular disease.
Sites / Locations
- CHU Sart Tilman
- Centro Riferimento Oncologico
- IRCCS Ospedale San Raffaele
- Vall d'Hebron Barcelona Hospital
- START Madrid. Fundacion Jimenez Diaz
- Centro Integral Oncologico Clara Campal
- NCCC Clinical Trials Pharmacy, Northern Centre for Cancer Care
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
MEN1309 (Step 1-Solid Tumors)/(Step 2-NHL)
Arm Description
Step1: Accelerated Titration Design with 1 single pt per cohort and double dose level per cohort until grade ≥ 2 drug related toxicity. Then, study reverts to 3+3 design. Any cohort in which 1 pt experiences a DLT (along ATD or 3+3) will be expanded up to 6 pts. Step2: MTD defined in Step 1, 3 MEN1309 dose levels will be tested (MTD-2, MTD-1, and MTD), with 6 pts per each dose level. A further MTD-3 level will be explored if 2 DLTs occur at the MTD-2 dose level.
Outcomes
Primary Outcome Measures
Maximum-Tolerated Dose (MTD)
Defined as the highest dose level at which no more than 1 of 6 patients experiences a DLT during the DLT assessment window.
Dose-Limiting Toxicity (DLT)
Adverse drug reactions (ADRs) that will be assessed during Cycle 1:
any grade ≥ 3 cardiac toxicity, new segmental wall-motion abnormalities, or cardiac troponin I or T elevation of grade 3 or higher;
any grade ≥ 3 elevations in total bilirubin, hepatic transaminases, or ALP levels; in patients with baseline grade 2 hepatic transaminase or ALP levels, an elevation to ≥ 10 x ULN is considered a DLT;
any grade 3 non-haematologic toxicity lasting > 7 days, (excluding diarrhea/nausea for which no adequate and optimal therapy has been implemented and alopecia);
any grade 3 vomiting lasting > 3 days despite adequate and optimal therapy;
any grade ≥ 4 non-haematologic toxicity;
any grade 4 thrombocytopenia or anemia;
any grade 4 neutropenia lasting > 7 days or febrile neutropenia;
any treatment delay of > 2 weeks because of delayed recovery from toxicity related to MEN1309 (except for alopecia).
Secondary Outcome Measures
Overall Survival
Timeframe between the first study drug administration and death from any cause.
Progression Free Survival
The Number of days between the first study administration to the date of first documented disease progression.
Preliminary Tumor Activity (RR)
Preliminary tumor activity (RR) Response Rate. RECIST v 1.1 assessment was performed using CT or MRI scan of the chest and abdomen (including adrenal glands). For the baseline assessment, CT or MRI scan were to be performed no more than 6 weeks (4+2 weeks) before the treatment start. Follow-up assessment were performed every other cycle starting from cycle 3 until the End of Study Visit.
Preliminary Antitumor Activity (DCR)
Preliminary Antitumor Activity (DCR) Disease control Rate. RECIST v 1.1 assessment was performed using CT or MRI scan of the chest and abdomen (including adrenal glands). For the baseline assessment, CT or MRI scan were to be performed no more than 6 weeks (4+2 weeks) before the treatment start. Follow-up assessment were performed every other cycle starting from cycle 3 until the End of Study Visit.
Preliminary Antitumor Activity (DOR)
Prliminary Antitumor Activity. Measure of the Duration of response. RECIST v 1.1 assessment was performed using CT or MRI scan of the chest and abdomen (including adrenal glands). For the baseline assessment, CT or MRI scan were to be performed no more than 6 weeks (4+2 weeks) before the treatment start. Follow-up assessment were performed every other cycle starting from cycle 3 until the End of Study Visit.
MEN1309 PK Parameter Cmax
Cmax is the maximum drug concentration
MEN1309 PK Parameter Ctrough
MEN1309 PK parameter Ctrough (Predose concentration)
MEN1309 Pharmacokinetic (PK) Parameter t1/2
MEN1309 Pharmacokinetic (PK) parameter t1/2 (terminal serum half-life)
MEN1309 Pharmacokinetic (PK) Parameter AUC
MEN1309 Pharmacokinetic (PK) parameter AUC (area under curve)
MEN1309 (PK) Parameter CL
Systemic clearance of MEN1309 Pharmacokinetic
MEN1309 Pharmacokinetic (PK) Parameter Vd
volume of distribution based on the terminal phase
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03403725
Brief Title
MEN1309 I.v. Infusion in Pts With CD205-positive Metastatic Solid Tumors and Relapsed or Refractory NHL Ph I Study
Acronym
CD205SHUTTLE
Official Title
Open-Label, Multicenter, Phase I Dose Escalation Study of MEN1309, a CD205 Antibody-Drug Conjugate,in Patients With CD205-Positive Metastatic Solid Tumors and Non-Hodgkin Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Terminated
Why Stopped
Terminated after achievement of MTD, without progressing to cohort expansion for Company decision.
Study Start Date
August 28, 2017 (Actual)
Primary Completion Date
October 22, 2019 (Actual)
Study Completion Date
January 8, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Menarini Group
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this clinical trial is to identify the highest dose of MEN1309 drug with acceptable safety profile and that can be used in patients affected by CD205-positive solid tumors and Non-Hodgkin Lymphoma
Detailed Description
This clinical trial will investigate the safety and activity of MEN1309 in patients with CD205-positive metastatic solid tumors and Non-Hodgkin Lymphoma who have tried other types of treatment for cancer without adequate response (or the cancer came back). CD205 is a protein present in certain types of cancer.
This is a Phase I study, which means that it is designed to look at several dose levels of a study drug in small groups of patients to find the dose that is well-tolerated and suitable to be administered in subsequent clinical trials in patients. The clinical trial is also looking at the effectiveness of the study drug. This is the first time the study drug will be given in humans.
The clinical trial consists of two sequential parts:
Part 1 involves patients with CD205-positive metastatic solid tumors and the main purpose of this part of the clinical trial is to determine the highest dose of the study drug that can be used safely in these type of cancers.
Part 2 involves patients with CD205-positive Non-Hodgkin Lymphoma and will test doses of MEN1309 which have demonstrated to be adequately tolerated in patients with solid tumors.
Patients participating to the clinical trial will take the study drug as intravenous infusion once every 3 weeks. The clinical trial includes four periods: a pre-screening period (to check if tumor is positive for CD205), a screening period (to check whether the participation to the clinical trial is right for patient), a treatment period (when patient receives the study drug), and a follow-up period (to check the health status of the patient after stopping study treatment).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Solid Tumors, Relapsed/Refractory Non-Hodgkin Lymphoma
Keywords
Solid Tumors, Non-Hodgkin Lymphoma, NHL, MEN1309, CD205, Relapsed, Refractory, R-R NHL, ADC, Antibody-Drug Coniugate, Metastatic Tumors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Cohort1 0.05mg/kg STEP 1 Solid Tumors Cohort2 0.10mg/kg STEP 1 Solid Tumors Cohort3 0.20mg/kg STEP 1 Solid Tumors Cohort4 0.40mg/kg STEP 1 Solid Tumors Cohort5 0.80mg/kg STEP 1 Solid Tumors Cohort6 1.60mg/kg STEP 1 Solid Tumors Cohort7 2.40mg/kg STEP 1 Solid Tumors Cohort8 3.36mg/kg STEP 1 Solid Tumors + GCSF Cohort7b 2.40mg/kg STEP 1 Solid Tumors +GCSF Cohort7c 2.00mg/kg STEP 1 Solid Tumors +GCSF Cohort5 0.80mg/kg STEP 2 NHL
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MEN1309 (Step 1-Solid Tumors)/(Step 2-NHL)
Arm Type
Experimental
Arm Description
Step1: Accelerated Titration Design with 1 single pt per cohort and double dose level per cohort until grade ≥ 2 drug related toxicity. Then, study reverts to 3+3 design. Any cohort in which 1 pt experiences a DLT (along ATD or 3+3) will be expanded up to 6 pts.
Step2: MTD defined in Step 1, 3 MEN1309 dose levels will be tested (MTD-2, MTD-1, and MTD), with 6 pts per each dose level. A further MTD-3 level will be explored if 2 DLTs occur at the MTD-2 dose level.
Intervention Type
Drug
Intervention Name(s)
MEN1309
Intervention Description
MEN1309 solution for intravenous infusion once every 3 weeks
Primary Outcome Measure Information:
Title
Maximum-Tolerated Dose (MTD)
Description
Defined as the highest dose level at which no more than 1 of 6 patients experiences a DLT during the DLT assessment window.
Time Frame
21-day period after the first dose
Title
Dose-Limiting Toxicity (DLT)
Description
Adverse drug reactions (ADRs) that will be assessed during Cycle 1:
any grade ≥ 3 cardiac toxicity, new segmental wall-motion abnormalities, or cardiac troponin I or T elevation of grade 3 or higher;
any grade ≥ 3 elevations in total bilirubin, hepatic transaminases, or ALP levels; in patients with baseline grade 2 hepatic transaminase or ALP levels, an elevation to ≥ 10 x ULN is considered a DLT;
any grade 3 non-haematologic toxicity lasting > 7 days, (excluding diarrhea/nausea for which no adequate and optimal therapy has been implemented and alopecia);
any grade 3 vomiting lasting > 3 days despite adequate and optimal therapy;
any grade ≥ 4 non-haematologic toxicity;
any grade 4 thrombocytopenia or anemia;
any grade 4 neutropenia lasting > 7 days or febrile neutropenia;
any treatment delay of > 2 weeks because of delayed recovery from toxicity related to MEN1309 (except for alopecia).
Time Frame
21-day period after the first dose
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Timeframe between the first study drug administration and death from any cause.
Time Frame
Through study completion, from "August 28, 2017" to "January 8, 2020" (2 years and 4 months)
Title
Progression Free Survival
Description
The Number of days between the first study administration to the date of first documented disease progression.
Time Frame
Through study completion, from "August 28, 2017" to "January 8, 2020" (2 years and 4 months)
Title
Preliminary Tumor Activity (RR)
Description
Preliminary tumor activity (RR) Response Rate. RECIST v 1.1 assessment was performed using CT or MRI scan of the chest and abdomen (including adrenal glands). For the baseline assessment, CT or MRI scan were to be performed no more than 6 weeks (4+2 weeks) before the treatment start. Follow-up assessment were performed every other cycle starting from cycle 3 until the End of Study Visit.
Time Frame
From Day1Visit1 to End of the treatment (At Baseline no more than 6 weeks before treatment and then every cycle starting from cycle 3 until End of Study)
Title
Preliminary Antitumor Activity (DCR)
Description
Preliminary Antitumor Activity (DCR) Disease control Rate. RECIST v 1.1 assessment was performed using CT or MRI scan of the chest and abdomen (including adrenal glands). For the baseline assessment, CT or MRI scan were to be performed no more than 6 weeks (4+2 weeks) before the treatment start. Follow-up assessment were performed every other cycle starting from cycle 3 until the End of Study Visit.
Time Frame
From Day1Visit1 to End of the treatment (At Baseline no more than 6 weeks before treatment and then every cycle starting from cycle 3 until End of Study)
Title
Preliminary Antitumor Activity (DOR)
Description
Prliminary Antitumor Activity. Measure of the Duration of response. RECIST v 1.1 assessment was performed using CT or MRI scan of the chest and abdomen (including adrenal glands). For the baseline assessment, CT or MRI scan were to be performed no more than 6 weeks (4+2 weeks) before the treatment start. Follow-up assessment were performed every other cycle starting from cycle 3 until the End of Study Visit.
Time Frame
From Day1Visit1 to End of the treatment (At Baseline no more than 6 weeks before treatment and then every cycle starting from cycle 3 until End of Study)
Title
MEN1309 PK Parameter Cmax
Description
Cmax is the maximum drug concentration
Time Frame
Cycle 1
Title
MEN1309 PK Parameter Ctrough
Description
MEN1309 PK parameter Ctrough (Predose concentration)
Time Frame
Pre-infusion Cycle 2
Title
MEN1309 Pharmacokinetic (PK) Parameter t1/2
Description
MEN1309 Pharmacokinetic (PK) parameter t1/2 (terminal serum half-life)
Time Frame
Cycle 1
Title
MEN1309 Pharmacokinetic (PK) Parameter AUC
Description
MEN1309 Pharmacokinetic (PK) parameter AUC (area under curve)
Time Frame
Cycle 1
Title
MEN1309 (PK) Parameter CL
Description
Systemic clearance of MEN1309 Pharmacokinetic
Time Frame
Cycle 1
Title
MEN1309 Pharmacokinetic (PK) Parameter Vd
Description
volume of distribution based on the terminal phase
Time Frame
Cycle 1
Other Pre-specified Outcome Measures:
Title
Correlation of CD205 Expression in Tumors With Clinical Activity of MEN1309 Assessed According to RECIST 1.1 or Cheson Criteria (2014)
Description
Exploratory Endpoint: Correlation of CD205 expression in tumors with clinical activity of MEN1309 assessed according to RECIST 1.1 or Cheson Criteria (2014) in terms of Response Rate, Disease control rate, duration of response, overall survival, and progression free survival.
N.B: No Data were available to assess this outcome.
Time Frame
Through study completion, from "August 28, 2017" to "January 8, 2020" (2 years and 4 months)
Title
Incidence of Anti-MEN1309 Antibodies
Description
Exploratory Endpoint: Immunogenicity analysis regarding the Incidence of anti-MEN1309 antibodies.
Time Frame
Day 1 of each Cycle (each cycle is 21 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main Inclusion Criteria:
Male or female patients aged ≥ 18 years.
Patients with:
confirmed diagnosis of advanced or metastatic solid tumor and diagnosis of multiple relapsed or refractory NHL;
progressive after last treatment received;
availability of archived tumor material, either as a block or slides;
measurable or evaluable disease by Response Evaluation Criteria in solid tumors guideline (RECIST v1.1) and by Cheson Criteria (The Lugano Classification, 2014) in NHL.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.
Neutrophil count ≥ 1,500/µL; platelets ≥ 100,000/µL; haemoglobin ≥ 9 g/dL.
Adequate renal and hepatic laboratory assessments.
Life expectancy of at least 2 months.
Woman of childbearing potential (WOCBP) who agrees to use highly effective contraception (see Appendix I).
Main Exclusion Criteria:
Central nervous system involvement (excluding treated stable cerebral metastasis, not requiring therapy to control symptoms in the last 60 days).
Pregnant or breastfeeding women.
Life-threatening illnesses other than solid tumors and NHL, uncontrolled medical conditions or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or put the study outcomes at risk.
Less than 2 previous cancer treatments, including high dose chemotherapy and ASCT, for NHL unless patient refuses standard therapy and/or is not eligible for ASCT.
Have significant, uncontrolled, or active cardiovascular disease.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Josep Tabernero Head, Medical Oncology Department, MD PhD
Organizational Affiliation
Vall d' Hebron Institute of Oncology (VHIO) P. Vall d'Hebron 119-129 08035 Barcelona, Spain
Official's Role
Study Chair
Facility Information:
Facility Name
CHU Sart Tilman
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Centro Riferimento Oncologico
City
Aviano
ZIP/Postal Code
33081
Country
Italy
Facility Name
IRCCS Ospedale San Raffaele
City
Milano
ZIP/Postal Code
20132
Country
Italy
Facility Name
Vall d'Hebron Barcelona Hospital
City
Barcelona
Country
Spain
Facility Name
START Madrid. Fundacion Jimenez Diaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Centro Integral Oncologico Clara Campal
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
NCCC Clinical Trials Pharmacy, Northern Centre for Cancer Care
City
Newcastle upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
MEN1309 I.v. Infusion in Pts With CD205-positive Metastatic Solid Tumors and Relapsed or Refractory NHL Ph I Study
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