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Neoplasm MalignantPhase 1NCT01673737

A Phase I/Ib Trial for the Evaluation of SAR260301 in Monotherapy or in Combination With Vemurafenib in Patients With Various Advanced Cancer

A Phase 1 study testing SAR260301 and Vemurafenib in people with Neoplasm Malignant, run by Sanofi at 4 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasm Malignant
What is being tested?
SAR260301 and Vemurafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
4 sitesin 2 countries
Study dates
Aug 2012to Feb 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 BRAF inhibitor after no more than 4 months treatment or with only partial response (<50% change in tumor volume) after 4 months of treatment (Part B) or vemurafenib naive (Part B escalation phase only): anterior scans must be available for patients having received BRAF inhibitor prior to entry into the study.
  • 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 analysis.

Who cannot join

  • 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.
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  • 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 in Part B.
  • Uveal melanoma as new primary malignancy in Part B
  • Prior history or ongoing uveitis
  • Mean QTc interval >470 msec (using QTcF formula) or any clinically significant QTc prolongation, history of Torsade de Pointes or malignant arrhythmias or conduction disturbances.
  • 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 abnormalities for the following electrolytes: potassium, magnesium and calcium.
  • 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.
  • Medical conditions requiring concomitant administration of medications with a narrow therapeutic window and metabolized by CYP1A2 or CYP2D6, and for which a dose reduction cannot be considered.
  • Medical conditions requiring concomitant administration of medications susceptible to prolong QTc interval.
  • The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

United States3 sites

  • Investigational Site Number 840001

    Boston, Massachusetts, 02114

  • Investigational Site Number 840101

    Boston, Massachusetts, 02115

  • Investigational Site Number 840002

    Houston, Texas, 77054

Other trials in United States

Canada1 site

  • Investigational Site Number 124001

    Toronto, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase I/Ib Study for the Evaluation of SAR260301, Administered Orally in Monotherapy in Patients With Advanced Solid Tumors or Lymphomas, and in Combination With Vemurafenib in Patients With Unresectable / Metastatic BRAF-mutated Melanoma

Primary Objective:

Part A - Monotherapy:

Read more
  • 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)
Read the detailed description

Study duration for one patient will include a period for inclusion (screening period) of up to 4 weeks, a treatment period of at least 4 weeks, and a end-of-study visit at 30 days following the last administration of study drug. The patient may continue treatment until disease progression, unacceptable toxicity or willingness to stop, followed by a minimum of 30-days follow-up.

Being tested
SAR260301, Vemurafenib
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SAR260301Drug

    Pharmaceutical form: film-coated tablets Route of administration: oral

  • VemurafenibDrug

    Pharmaceutical form: film-coated tablets Route of administration: oral

Study groups in NCT01673737
Study groupRoleWhat they receive
Part A MonotherapyExperimentalDose escalation of daily or twice daily SAR260301 within a 28-day cycle, followed by an expansion phase at the maximal tolerated dose
Receives: Drug: SAR260301
Part B CombinationExperimentalDose escalation of twice-daily SAR260301 within a 28-day cycle and in combination with 720 or 960 mg twice daily of Vemurafenib, followed by an expansion phase at the maximal tolerated dose of SAR260301 in combination
Receives: Drug: SAR260301; Drug: Vemurafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximal tolerated dose (MTD) of SAR260301 in monotherapy (Study Part A)

    Measured: Day 28

  2. Maximal tolerated dose (MTD) of SAR260301 in combination with vemurafenib (Study Part B)

    Measured: Day 28

Secondary outcomes (9)

  1. Number of patients with treatment emergent events

    Measured: Up to 2 years

  2. Assessment of PK parameters for SAR260301 and vemurafenib, including tmax, Cmax, AUC, Rac (Day 28/Day1), half-life, CL, Ctrough

    Measured: 4 weeks

  3. Assessment of PK parameters for SAR260301 including tmax, Cmax, AUC fasting and fed (food effect)(Only part A)

    Measured: Up to 8 weeks

  4. Assessment of urine excretion of SAR2690301 (Part A)

    Measured: 12-24 hours at Day 28

  5. Assessment of potential for CYP induction (4beta-hydroxycholesterol)(Part A)

    Measured: Up to 15 days

  6. Assessment of PK parameter Rac (Day 28/Day 1) on AUC and Cmax

    Measured: 4 weeks

  7. Assessment of PD parameter Serine/threonine protein kinase Akt (AKT) phosphorylation in blood platelets

    Measured: 4 weeks

  8. Assessment of PD parameter AKT phosphorylation in tumor (expansion phase only)

    Measured: 15 days

  9. Assessment of preliminary antitumor activity as documented by tumor response (defined by RECIST1.1 criteria for solid tumors, international working group (IWG) and revised response for lymphomas, and tumor markers when relevant)

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2012 (estimated)
  2. Study startAug 2012
  3. Primary completionFeb 2015
  4. Study completionFeb 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01673737
Sponsor's protocol ID
TCD12739
Other IDs
U1111-1129-2696
Status last verified
Apr 2015
First submitted
23 Aug 2012
Last updated
10 Apr 2015
Results posted
No
Data monitoring committee
No

Publications

  • Bedard PL, Davies MA, Kopetz S, Juric D, Shapiro GI, Luke JJ, Spreafico A, Wu B, Castell C, Gomez C, Cartot-Cotton S, Mazuir F, Dubar M, Micallef S, Demers B, Flaherty KT. First-in-human trial of the PI3Kbeta-selective inhibitor SAR260301 in patients with advanced solid tumors. Cancer. 2018 Jan 15;124(2):315-324. doi: 10.1002/cncr.31044. Epub 2017 Oct 4.

    PubMed 28976556

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SAR260301 and Vemurafenib in people with Neoplasm Malignant, run by Sanofi at 4 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximal tolerated dose (MTD) of SAR260301 in monotherapy (Study Part A) (time frame: Day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01673737, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2015.

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