- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01436565
A Study of Investigational SAR256212 in Combination With SAR245408 in Patients With Solid Tumor Cancers
June 12, 2014 updated by: Sanofi
A Phase 1b Dose-escalation Study of the Safety and Pharmacokinetics of SAR245408 Administered in Combination With SAR256212 in Patients With Solid Tumor Cancers
Primary Objective:
- To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of SAR245408 administered in combination with SAR256212 in adult patients with locally advanced or metastatic solid tumors.
Secondary Objectives:
- To characterize the global safety profile of SAR245408 in combination with SAR256212
- To evaluate the pharmacokinetic (PK) profile of SAR245408 and SAR256212 used in combination
- To evaluate the objective response rate (ORR) and tumor volume change (for expansion cohort only)
- To determine the immunogenicity of SAR256212 as administered with SAR245408
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
There is a 28 day screening period followed by 28 day cycles (21 day cycle for the every three week dosing regimen, if used) .
Patients will continue to receive SAR245408/SAR256212 as long as there is clinical benefit or until a study withdrawal criterion is met.
The last posttreatment visit will be 60 days after the last dose or until IMP-related toxicities have resolved or are deemed irreversible, whichever is later.
Study Type
Interventional
Enrollment (Actual)
26
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
-
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Investigational Site Number 840001
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Brookline, Massachusetts, United States, 02115
- Investigational Site Number 840101
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Tennessee
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Nashville, Tennessee, United States, 37232
- Investigational Site Number 840002
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-
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:
- Metastatic or locally advanced nonhematological cancer, for which no alternative therapy is available
- Written informed consent
For dose expansion only:
- Patient's tumor harbors activating mutations in phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA)
- Tissue from archived sample
- Measurable and evaluable disease
Exclusion criteria:
- Patient less than 18 years old
- ECOG (Eastern Cooperative Oncology Group) performance status >2
- Any serious active disease or comorbid condition, which, in the opinion of the Investigator, could interfere with the safety of the patient or the ability of the patient to comply with the study, or with the interpretation of the results
- Poor bone marrow reserve as defined by absolute neutrophils count <1.5 x 109/L or platelets <100 x 109/L
Poor organ function as defined by 1 of the following:
- Total bilirubin >1.5 x ULN (upper limit of normal)
- AST (aspartate aminotransferase) and/or ALT (alanine aminotransferase) >2.5 x ULN
- Serum creatinine >1.5 x ULN and/or creatinine clearance <60 mL/min
- PT/ (INR) (prothrombin time) (International Normalized Ratio) and/or partial thromboplastin time (PTT) test results ≥1.3 ULN
- Pregnant or breast-feeding women
- No use of effective birth control methods, when applicable
- No resolution of all specific toxicities (excluding alopecia) related to any prior anticancer therapy to Grade ≤1 according to the NCI common terminology criteria for adverse events (CTCAE) v.4.0
- Any of the following within 6 months prior to enrollment: myocardial infarction, severe/unstable angina, or coronary/peripheral artery bypass graft surgery, clinically symptomatic and uncontrolled cardiovascular disease, or clinically significant cardiac arrhythmias (Grade 3/4)
- Baseline corrected QT interval (QTc) >460 ms.
- NYHA Class III (New York Heart Association) or IV congestive heart failure or LVEF (left ventricular ejection fraction) < the lower limit of normal (LLN) for institution
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including cytomegalovirus, Epstein-Barr virus, toxoplasmosis, and hepatitis B and C, positive for the human immunodeficiency virus (HIV), hypertension, or uncontrolled diabetes.
- Previous treatment with a selective PI3K inhibitor (phosphoinositide-3-kinase, catalytic, alpha polypeptide), mTOR (mechanistic target of rapamycin) inhibitor, or AKT inhibitor (v-akt murine thymoma viral oncogene homolog 1)
- Known hypersensitivity to the investigational medicinal product(s) or to its excipients, or patient who has had hypersensitivity reactions to fully human monoclonal antibodies
- Cytotoxic chemotherapy (including investigational cytotoxic agents) or biologic agents (antibodies, immune modulators, cytokines) within 4 weeks, or nitrosoureas or mitomycin C within 6 weeks, before the first dose of study treatment
- Prior radiation therapy within 2 weeks before the first dose of study treatment
- Prior major surgery from which the patient has not recovered or stabilized
- Any other investigational therapy within 4 weeks prior to the first dose of study treatment
- Brain tumor or brain metastasis are considered eligible if the patient has not received radiation therapy for brain metastasis within 2 weeks of enrollment and has been on a stable dose of steroids for 2 or more weeks
- Ongoing anticoagulation with therapeutic doses of warfarin (low-dose warfarin ≤1 mg/day is permitted).
- HBA1C (hemoglobin A1c) >7 or any patient requiring medication for glycemic control
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
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: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: dose escalation and expansion
SAR245408 taken every day in the morning: no eating 2 hours prior and 1 hour after dose; SAR256212 will be given weekly by IV infusion over 1 hour, right after the SAR245408 oral dose
|
Pharmaceutical form:solution Route of administration: Intravenous Pharmaceutical form:tablet Route of administration: oral |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Maximum tolerated dose
Time Frame: 2 months to 12 months
|
2 months to 12 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Peak and trough levels of SAR256212 and SAR245408
Time Frame: 1 month to 6 months
|
1 month to 6 months
|
Pharmacodynamic change in ErbB3 protein and mRNA levels as well as components of the PI3K pathway will be measured
Time Frame: 1 month to 6 months
|
1 month to 6 months
|
Number of participants with adverse events
Time Frame: 1 month to 2 years
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1 month to 2 years
|
overall response rate
Time Frame: 2 months to 2 years
|
2 months to 2 years
|
Number of patients who develop anti-MM-121 antibodies
Time Frame: 1 month to 6 months
|
1 month to 6 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
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
November 1, 2011
Primary Completion (Actual)
May 1, 2014
Study Completion (Actual)
May 1, 2014
Study Registration Dates
First Submitted
September 7, 2011
First Submitted That Met QC Criteria
September 16, 2011
First Posted (Estimate)
September 19, 2011
Study Record Updates
Last Update Posted (Estimate)
June 13, 2014
Last Update Submitted That Met QC Criteria
June 12, 2014
Last Verified
June 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- TCD11721
- U1111-1121-4146 (Other Identifier: UTN)
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.
Clinical Trials on Solid Tumor Cancers
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Memorial Sloan Kettering Cancer CenterActive, not recruitingMetastatic Solid Tumor Cancers | Locally Advanced Solid Tumor CancersUnited States
-
AbbottCompletedSolid Tumor CancersUnited States
-
Agenus Inc.CompletedAdvanced Solid Cancers | Advanced Solid Cancers Refractory to PD-1United States
-
Novartis PharmaceuticalsRecruitingContinued Access to Study Treatment(s), Cancers With a Mass, Bulky Tumor, Nodule, Lump, Advanced Cancer, Advanced Solid Tumors, Advanced Solid MalignanciesSpain, Taiwan, United States, Singapore, France
-
Hoffmann-La RocheCompletedSolid CancersUnited States, Belgium, France, Spain
-
Hoffmann-La RocheCompleted
-
Medical University of South CarolinaCompletedSolid CancersUnited States
-
Genentech, Inc.Completed
-
Genentech, Inc.Completed
Clinical Trials on MM-121 (SAR256212)
-
Merrimack PharmaceuticalsSanofiCompletedAdvanced Solid TumorsUnited States
-
Merrimack PharmaceuticalsSanofiCompletedLocally Advanced/Metastatic or Recurrent Ovarian Cancer, Fallopian Tube Cancer, | Primary Peritoneal Cancer or Endometrial Cancer | Locally Advanced/Metastatic Her2 Non Overexpressing Breast CancerUnited States
-
Merrimack PharmaceuticalsSanofiCompletedER Positive, Her2 Negative Breast Cancer Patients | Triple Negative Breast Cancer PatientsUnited States
-
Merrimack PharmaceuticalsSanofiCompletedFallopian Tube Cancer | Epithelial Ovarian Cancer | Peritoneal CancerUnited States
-
Merrimack PharmaceuticalsCompletedCarcinoma, Non-Small-Cell LungSpain, Taiwan, United States, Canada, Korea, Republic of, Germany
-
Merrimack PharmaceuticalsSanofiCompletedColorectal Cancer | Triple Negative Breast Cancer | Non-small Cell Lung Cancer | Squamous Cell Head and Neck Cancer | Other Tumors With EGFR DependenceUnited States
-
Merrimack PharmaceuticalsTerminatedColorectal Cancer | Squamous Cell Carcinoma of the Head and Neck | Non-small Cell Lung CancerUnited States
-
Merrimack PharmaceuticalsCompletedHer2 Negative Breast Cancer PatientsUnited States, Spain, Canada, Germany, Russian Federation
-
Valeant PharmaceuticalsUnknown
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Merrimack PharmaceuticalsSanofiCompletedSolid TumorsFrance, United States