A Study of Investigational SAR256212 in Combination With SAR245408 in Patients With Solid Tumor Cancers

This study has been completed.
Sponsor:
Collaborator:
Merrimack Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01436565
First received: September 7, 2011
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

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

Condition Intervention Phase
Solid Tumor Cancers
Drug: MM-121 (SAR256212)
Drug: SAR245408
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Dose-escalation Study of the Safety and Pharmacokinetics of SAR245408 Administered in Combination With SAR256212 in Patients With Solid Tumor Cancers

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: 2 months to 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Peak and trough levels of SAR256212 and SAR245408 [ Time Frame: 1 month to 6 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Number of participants with adverse events [ Time Frame: 1 month to 2 years ] [ Designated as safety issue: Yes ]
  • overall response rate [ Time Frame: 2 months to 2 years ] [ Designated as safety issue: No ]
  • Number of patients who develop anti-MM-121 antibodies [ Time Frame: 1 month to 6 months ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: November 2011
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: MM-121 (SAR256212)

Pharmaceutical form:solution

Route of administration: Intravenous

Drug: SAR245408

Pharmaceutical form:tablet

Route of administration: oral


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01436565

Locations
United States, Massachusetts
Investigational Site Number 840001
Boston, Massachusetts, United States, 02115
Investigational Site Number 840101
Brookline, Massachusetts, United States, 02115
United States, Tennessee
Investigational Site Number 840002
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Sanofi
Merrimack Pharmaceuticals
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01436565     History of Changes
Other Study ID Numbers: TCD11721, U1111-1121-4146
Study First Received: September 7, 2011
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 21, 2014