A Phase I/Ib Trial for the Evaluation of SAR260301 in Monotherapy or in Combination With Vemurafenib in Patients With Various Advanced Cancer
Diagnosis: Solid Tumor/Phase I
NCT ID: NCT01673737
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 12-290
Primary Objective: Part A - Monotherapy: - To determine the maximum tolerated dose (MTD) of SAR260301 administered as monotherapy and either on a once or twice daily schedule, to patients with advanced solid tumors or lymphomas. Part B - Combination: - To determine the maximum tolerated dose (MTD) of SAR260301 administered in combination with the recommended standard dosage of Vemurafenib to patients with unresectable / metastatic v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutated melanoma. Secondary Objectives: - To characterize the overall safety and tolerability profile of SAR260301 administered as monotherapy (Part A) and in combination with Vemurafenib (Part B). - To characterize the pharmacokinetic (PK) profile of SAR260301 administered as monotherapy (Part A) and in combination with Vemurafenib (Part B) as well as Vemurafenib PK in combination with SAR260301 (Part B) - To evaluate food effect on SAR260301 PK (Part A) - To assess preliminary antitumor activity according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1 criteria). - To assess preliminary antitumor activity using volumetric computed tomography (CT) or magnetic resonance imaging(MRI) - To evaluate the pharmacodynamic (PD) effects of SAR260301 on blood and tumor. - To evaluate PK/PD relationships. - To identify the recommended phase 2 dose of SAR260301 in combination with Vemurafenib (RP2D) (Part B only) - To assess potential induction effect of SAR260301 on cytochrome P450 (CYP) isoenzyme 3A (CYP3A) (Part A)
Massachusetts General Hospital, Dana-Farber Cancer Institute, Brigham and Women's Hospital
Keith Flaherty, MD,
Massachusetts General Hospital
Geoffrey Shapiro, MD, PhD,
Dana-Farber Cancer Institute
Massachusetts General Hospital:
Cancer Trials Call Center, 877-789-6100
Dana-Farber Cancer Institute:
Andrew Wolanski, 617-632-6623,
Inclusion criteria :
- Age ≥18 years old
- Locally advanced or metastatic solid tumor disease as well as lymphoma for which no
alternative therapy is available (Part A)
- Unresectable / metastatic BRAF-mutated melanomas, progressing on Vemurafenib (Part B)
or Vemurafenib naive (Part B escalation phase only).
- At least one measurable lesion by RECIST v1.1
- Archived primary tumor biopsies or surgical specimens, or biopsies of recurrence or
metastasis, will be requested for all subjects for predictive markers of response
- ECOG performance status >1
- Concurrent treatment with any other anticancer therapy
- Patient with reproductive potential (female and male) who do not agree to use an
accepted effective method of contraception during the study treatment period and for
at least 6 months following completion of study treatment.
- Pregnancy or breast-feeding
- Any malignancy related to immunodeficiency virus (HIV) or solid organ transplant;
history of known HIV, unresolved viral hepatitis
- Subjects with brain metastases of non-central nervous system (CNS) primary tumors are
excluded if their lesions are larger than 1 cm in the longest dimension, symptomatic
or changed in size in the latest scan compared to the previous scan. Subjects must
not require corticosteroid treatment or have received treatment for brain metastases
for at least one month prior to study entry.
- Inadequate haematological function
- Inadequate renal function
- Inadequate liver function
- Non-resolution of any prior treatment related toxicity to < Grade 2, except for
alopecia according to National Cancer Institute Common Terminology Criteria for
Adverse Events (NCI CTCAE) v4.03.
- Any major surgery within the last 28 days.
- History of congenital platelet function defect or bleeding diathesis.
- Abnormal platelet function using platelet function assay PFA 100® including
aggregation time >122 seconds using the collagen/ADP cartridge, and/or >183 seconds
using the collagen/epinephrine cartridge.
- Current use of aspirin, clopidogrel, ticlopidine, prasugrel or ticagrelor.
- Abnormal coagulation parameters: Prothrombin time (PT)/ international normalized
ratio (INR) or activated partial thromboplastin time (aPTT) >1.3X ULN. Prophylactic
but not therapeutic anticoagulants are permitted.
- Any of the following within 6 months prior to study enrolment: peptic ulcer disease,
erosive oesophagitis, or gastritis, infectious or inflammatory bowel disease,
diverticulitis, GI perforation, intestinal obstruction and GI hemorrhage.
- Patients with history of chronic renal diseases, interstitial nephritis, or with
uncontrolled or unresolved acute renal failure.
- Hemoptysis within the past 3 months.
- Patients with known Gilbert's syndrome.
- Prior hypersensitivity reaction or severe dermatologic reactions such as Steven's
Johnsons syndrome and toxic epidermal necrolysis (TENS) to Vemurafenib.
- Prior history or ongoing uveitis
- Mean QTc interval >500 msec (using QTcF formula) or any clinically significant QTc
prolongation, history of Torsade de Pointes or malignant arrhythmias or conduction
- Other clinically significant ECG abnormalities including 2nd degree (Mobitz Type II),
familial history of long QT syndrome and 3rd degree atrioventricular block.
- Congestive heart failure
- Uncontrolled or untreated hypertension
- Uncorrectable serum electrolyte abnormalities
- Medical conditions having to require concomitant administration of strong CYP3A4
inhibitors or inducers 2 weeks prior to study treatment or 5 elimination half-life of
the drug, whichever is longest.
The above information is not intended to contain all considerations relevant to a
patient's potential participation in a clinical trial.