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Oral SAR245408 (XL147) and Oral MSC1936369B in Patients With Locally Advanced or Metastatic Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01357330
First received: May 16, 2011
Last updated: August 22, 2012
Last verified: August 2012
  Purpose

Primary Objective:

- To determine the maximum tolerated dose(s) (MTD) and the recommended Phase 2 dose(s) (RP2D) of SAR245408 and MSC1936369B when combined in adult subjects with locally advanced or metastatic solid tumors.

Secondary Objective:

  • To characterize the safety and tolerability of SAR245408 and MSC1936369B combination therapy administered orally to adult patients with locally advanced or metastatic solid tumors
  • To evaluate the pharmacokinetic (PK) profile of SAR245408 and MSC1936369B when used in combination
  • To evaluate the pharmacodynamic (PD) effect of the SAR245408/MSC1936369B combination by assessing target and pathway inhibition

Condition Intervention Phase
Solid Tumors
Drug: SAR245408 (XL147)
Drug: MSC1936369B
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Phase 1 Dose Escalation Study of Combination Therapy With Oral SAR245408 (XL147) and Oral MSC1936369B in Patients With Locally Advanced or Metastatic Solid Tumors

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Identification of maximum tolerated dose [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of participants with treatment emergent adverse events [ Time Frame: up to 4 years ] [ Designated as safety issue: Yes ]
  • Pharmakokinetic parameters of SAR245408: Cmax [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
  • Pharmakokinetic parameters of SAR245408: Tmax [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
  • Pharmakokinetic parameters of SAR245408:AUCι [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
  • Pharmakokinetic parameters of MSC1936369B: Cmax [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
  • Pharmakokinetic parameters of MSC1936369B: Tmax [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
  • Pharmakokinetic parameters of MSC1936369B: AUCι [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: May 2011
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation
Dose escalation phase The starting dose of SAR245408 will be 25-mg once daily (up to 200-mg). The starting dose of MSC1936369B will be 15- mg once daily (up to 90-mg)
Drug: SAR245408 (XL147)
Pharmaceutical form:capsule and tablet Route of administration: oral
Drug: MSC1936369B
Pharmaceutical form:capsule Route of administration: oral

Detailed Description:

The duration of the study will include a period for screening of up to a maximum of 28 days, a pretreatment evaluation period of up to 5 days, the on-treatment period, followed by a minimum of 30-day follow-up after the last study drug administration.

The patient may continue study treatment until disease progression, unacceptable toxicity, or consent withdrawal.

The study will have 2 parts:

  • Part one - Dose Escalation
  • Part Two - Expansion. At the defined maximum tolerated doses (MTD(s), additional patients will be enrolled to collect safety, Pharmacokinetic, and Pharmacodynamic data
  Eligibility

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

Inclusion criteria:

Patient with advanced solid tumors for which there is no approved or curative therapy:

  • has any advanced solid tumor with diagnosed alteration in 1 or more genes of the PI3K, and mitogen-activated protein kinase (MAPK) pathways and/or
  • has a histologically or cytologically confirmed diagnosis of 1 of the following solid tumors: pancreatic, thyroid, colorectal, non-small cell lung, endometrial, renal, breast, ovarian carcinoma and melanoma

Exclusion criteria:

The patient has previously been treated with a PI3K inhibitor or a Mitogen-activated protein extracellular signal-regulated kinase (MEK) inhibitor

The patient has received:

  • Chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any other anticancer therapy within 28 days or 5 half lives for noncytotoxics (whichever is shorter) of Day 1 of trial drug treatment (6 weeks for nitrosureas or mitomycin C)
  • Any investigational agent within 28 days of Day 1 of trial drug treatment The patient is currently receiving anticoagulation therapy with therapeutic doses of warfarin (low-dose warfarin ≤1 mg/day, heparin, and low-molecular weight heparins are permitted) History of central nervous system metastases The patient has had congestive heart failure, unstable angina, a myocardial infarction, cardiac conduction abnormality or pacemaker or a stroke within 3 months of entering the study. The patient has retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), history of uveitis, or history of retinal vein occlusion, or has medically relevant abnormalities identified on screening ophthalmologic examination.

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: NCT01357330

Locations
United States, Massachusetts
Investigational Site Number 840001
Boston, Massachusetts, United States, 02114
Investigational Site Number 840002
Boston, Massachusetts, United States, 02115
United States, Tennessee
Investigational Site Number 840003
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01357330     History of Changes
Other Study ID Numbers: TCD11742, U1111-1117-9893
Study First Received: May 16, 2011
Last Updated: August 22, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
locally advanced or metastatic

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on November 27, 2014