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A Phase 1b Dose-escalation Study of the Safety and Pharmacokinetics of SAR245408 Administered in Combination With SAR256212 in Patients With Solid Tumor Cancers

Phase 1
18 Years
Open (Enrolling)
Solid Tumor Cancers

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Trial Information

A Phase 1b Dose-escalation Study of the Safety and Pharmacokinetics of SAR245408 Administered in Combination With SAR256212 in Patients With Solid Tumor Cancers

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.

Inclusion 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

- 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

- 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

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Outcome Time Frame:

2 months to 12 months

Safety Issue:


Principal Investigator

Clinical Sciences & Operations

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

November 2011

Completion Date:

September 2014

Related Keywords:

  • Solid Tumor Cancers
  • Neoplasms



Investigational Site Number 840001Boston, Massachusetts  02114
Investigational Site Number 840002Nashville, Tennessee  37232
Investigational Site Number 840101Boston, Massachusetts  02115