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An Open-Label, Phase 1/Phase 2, Single-Agent Study of CEP-32496 in Patients With Advanced Solid Tumors in Phase 1 and in Patients With Advanced Melanoma and Metastatic Colorectal Cancer With BRAF Mutation in Phase 2


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Solid Tumors, Melanoma, Metastatic Colorectal Cancer

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Trial Information

An Open-Label, Phase 1/Phase 2, Single-Agent Study of CEP-32496 in Patients With Advanced Solid Tumors in Phase 1 and in Patients With Advanced Melanoma and Metastatic Colorectal Cancer With BRAF Mutation in Phase 2


The primary objective of Phase 1 is to determine the recommended Phase 2 dose (RP2D) of
CEP-32496. The primary objective of Phase 2 is to evaluate the antitumor activity of
CEP-32496 at the RP2D, as assessed by objective response rate (complete response [CR] or
partial response [PR]) using Response Evaluation Criteria in Solid Tumors version 1.1
(RECIST v1.1) in patients with advanced unresectable melanoma and metastatic colorectal
cancer with BRAF mutation. Four groups of patients will be treated in Phase 2:

- group A: patients with advanced unresectable melanoma with acquired resistance to BRAF
inhibitors (ie, patients who have achieved a CR or PR as a best response to treatment
with a prior BRAF inhibitor and subsequently became resistant) and patients who
discontinued treatment with a BRAF inhibitor due to intolerance

- group B: patients with advanced unresectable melanoma with primary resistance to BRAF
inhibitors (ie, patients who maintained stable disease or had progressive disease as a
best response to treatment with a prior BRAF inhibitor)

- group C: patients with advanced unresectable melanoma who are naïve to treatment with
BRAF inhibitors

- group D: patients with metastatic colorectal cancer who are naïve to treatment with
BRAF inhibitors

Each phase of this study will consist of a 28-day screening period. Patients will be treated
in 28-day treatment cycles until disease progression, unacceptable toxicity, withdrawal of
consent, or protocol specified parameters to stop treatment. Patients in Phase 1 will be
followed for a minimum of 6 months after the last dose of study treatment, and patients in
Phase 2 will be followed to collect further anticancer information for up to 12 months after
the end-of-treatment visit for the last discontinued patient on the study.


Inclusion Criteria:



1. Phase 1 only: Patients must have histological or cytological evidence of a solid
tumor which is refractory to available therapy or for which no effective standard
therapy exists. The patient may have received monotherapy with 1 or more BRAF
inhibitors.

2. Phase 2 only: Patients must have histologically or cytologically confirmed advanced
unresectable cutaneous melanoma (Stage IIIC and IV per American Joint Committee on
Cancer [AJCC]) and BRAF V600E or BRAF V600K mutation or relapsed/refractory
metastatic colorectal cancer and BRAF V600E or BRAF V600K mutation.

- Previously existing BRAF V600E or BRAF V600K mutation results using a test
approved by the FDA or from an accredited laboratory (CLIA certified or
equivalent) will be accepted.

- If documented results are not available, then archived or fresh tumor tissue
samples suitable for biomarker analysis must be available for testing by an
accredited laboratory (CLIA certified or equivalent).

3. Patients may have received any number of prior systemic treatments for their cancer.
However, for patients in Phase 2, groups A and B, prior treatment with only 1 BRAF
inhibitor or MEK inhibitor monotherapy is permitted. Phase 2 patients with metastatic
colorectal cancer (group D) must have received 1 or more fluoropyrimidine,
oxaliplatin, or irinotecan based chemotherapy.

4. The patient has measurable disease and documented progression on or after last prior
treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) version
1.1

5. The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
of 0 or 1 for Phase 1 or 0, 1, or 2 for Phase 2.

6. Other inclusion criteria apply.

Exclusion Criteria:

1. For patients in Phase 1 only, the patient has primary brain tumor or ocular melanoma.

2. For patients in Phase 2 groups C or D only, the patient received previous treatment
with a selective BRAF inhibitor or MEK inhibitor (prior treatment with sorafenib
allowed).

3. The patient was treated with systemic anticancer therapy or investigational agent
within 3 weeks prior to start of study drug treatment (6 weeks for bevacizumab and
immunotherapy).

4. The patient had major surgery within 21 days or less prior to starting of the study
drug or who have not recovered from adverse effects of such therapy.

5. The patient had radiotherapy within 2 weeks prior to start of study drug treatment.

Patients must have recovered from all radiotherapy-related toxicities.

6. The patient has known central nervous system (CNS) metastases. Patients with any
clinical signs of CNS metastases must have a CT or MRI of the brain to rule out CNS
metastases in order to be eligible for participation in the study. Patients who have
had brain metastases treated with radiotherapy or surgically removed with no residual
disease confirmed by imaging should be clinically stable and off corticosteroid
treatment at least 3 weeks prior to start of study drug treatment.

7. The patient has a QTc interval greater than 470 msec.

8. The patient has a major active infection requiring parenteral antibiotics.

9. The patient has a severe or unstable medical condition such as congestive heart
failure (New York Heart Association [NYHA] Class III or IV), ischemic heart disease,
uncontrolled hypertension, uncontrolled diabetes mellitus, psychiatric condition, as
well as an ongoing cardiac arrhythmia requiring medication (≥grade 2, according to
NCI Common Terminology Criteria for Adverse Events [CTCAE] v4.03), myocardial
infarction within 6 months prior to starting study treatment, or any other
significant or unstable concurrent medical illness that in the opinion of the
investigator would preclude protocol therapy.

10. Other exclusion criteria apply.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective Response Rate

Outcome Description:

The primary efficacy variable is the objective response rate calculated as the number of responders (i.e., CR or PR) in each patient group divided by the number of evaluable patients in that patient group.

Outcome Time Frame:

Approximately 12 months

Safety Issue:

No

Authority:

United States: Food and Drug Administration

Study ID:

C32496/1105

NCT ID:

NCT01877811

Start Date:

June 2013

Completion Date:

April 2017

Related Keywords:

  • Solid Tumors
  • Melanoma
  • Metastatic Colorectal Cancer
  • BRAF inhibitor
  • solid tumors
  • melanoma
  • colorectal cancer
  • Colorectal Neoplasms
  • Melanoma
  • Neoplasms

Name

Location

Teva Investigational Site 10672Duarte, California  
Teva Investigational Site 10673Fort Myers, Florida  
Teva Investigational Site 10670Detroit, Michigan  
Teva Investigational Site 10671St. Louis, Missouri  
Teva Investigational Site 10669Philadelphia, Pennsylvania