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A Phase I/II Study of CC-4047 in Combination With Gemcitabine in Subjects With Untreated Advanced Carcinoma of the Pancreas


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Pancreatic Cancer

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Trial Information

A Phase I/II Study of CC-4047 in Combination With Gemcitabine in Subjects With Untreated Advanced Carcinoma of the Pancreas


Phase I

Primary:

• To determine the maximum tolerated dose (MTD) and evaluate the safety profile of oral
CC-4047 given on days 1-21 in combination with gemcitabine on days 1, 8, and 15 every 28
days in subjects with advanced pancreatic carcinoma.

Secondary:

• To explore the anti-tumor activity of the combination of CC-4047 and gemcitabine as
combination therapy in subjects with advanced pancreatic carcinoma.

Phase II

Primary:

• To explore the anti-tumor activity of the combination of CC-4047 on days 1-21 and
gemcitabine on days 1, 8, and 15 every 28 days in subjects with advanced pancreatic
carcinoma.

Secondary:

• To evaluate the safety profile of the combination of CC-4047 and gemcitabine as
combination therapy in subjects with advanced pancreatic carcinoma.


Inclusion Criteria:



1. Understand and voluntarily sign an informed consent form.

2. Age ≥ 18 years at the time of signing the informed consent form.

3. Must be able to adhere to the study visit schedule and other protocol requirements.

4. Histological or cytological documentation of adenocarcinoma of the pancreas with
metastases not amenable to curative surgery or definitive radiation. Patients with
locally advanced disease are not eligible.

5. Radiographic or clinical evidence of measurable advanced metastatic pancreatic
carcinoma. Subjects must have measurable disease according to the international
criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST)
Committee for target lesions (see Appendix 14.2).

6. Subjects may have been previously treated with adjuvant radiation therapy and
5-fluorouracil or Gemzar as a radiosensitizer in the adjuvant setting if they
currently have evidence of progression. Following completion of XRT, no further
adjuvant chemotherapy with either Gemzar or 5-FU is permitted. No prior Gemzar® for
metastatic disease or for primary treatment of locally advanced disease is allowed.
Gemzar® used solely as a radiation sensitizer in the adjuvant setting is permitted.

7. ECOG performance status of 0 or 1.

8. Females of childbearing potential (FCBP)† must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL 10 - 14 days prior to and
again within 24 hours of starting CC-4047 and must either commit to continued
abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
control, one highly effective method and one additional effective method AT THE SAME
TIME, at least 4 weeks before she starts taking CC-4047. FCBP must also agree to
ongoing pregnancy testing. Men must agree not to father a child and agree to use a
condom if his partner is of child bearing potential. All patients must be counseled
at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
(see Appendix 14.6).

Exclusion Criteria:

1. Pregnant or lactating females.

2. Any serious medical condition or psychiatric illness that prevents the study subject
from signing the informed consent form or places the study subject at an unacceptable
risk if he or she participates in the study.

3. Prior therapy with CC-4047, lenalidomide, or thalidomide.

4. Prior use of systemic therapy for the treatment of adenocarcinoma of the pancreas
with the exception of 5-fluorouracil or Gemzar® as a radiosensitizer in the adjuvant
setting

5. Concurrent use of any other anti-cancer agents.

6. Any of the following laboratory abnormalities:

- Absolute neutrophil count (ANC) < 1,500 cells/mm3 (1.5 x 109/L)

- Platelet count < 100,000 cells/ mm3 (100 x 109/L)

- Serum creatinine > 2.5 mg/dL (221 μmol/L)

- Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN); in case of liver
metastases > 5 x ULN

- Serum total bilirubin > 2.0 mg/dL (34 μmol/L)

7. Surgery or radiation therapy within 14 days of study enrollment as outlined below.

- Surgery within 14 days of the start of study (patients must have recovered from
effects of surgery; 7 days may be considered for minor procedures).

- Palliative radiation therapy within 14 days of the start of study. The radiation
therapy may not be to the only site of measurable disease. Adjuvant therapy is
permitted in accordance with the inclusion criteria.

8. Prior history of malignancy (except basal cell or squamous cell carcinoma or
carcinoma in situ of the cervix or breast, localized prostate cancer with PSA < 1.0
mg/dL) unless the subject has been free of disease for ≥ 3 years.

9. Known brain or leptomeningeal disease (CT scan or MRI of the brain required only in
case of clinical suspicion of central nervous system involvement).

10. Grade ≥ 2 neuropathy.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Determination of Maximum Tolerated Dose (MTD), The Dose of Study Drug(s) Which Causes <33% of Patients Treated to Experience Unacceptable Side Effects

Outcome Description:

Unacceptable side effects or dose-limiting toxicities (DLTs) were defined as follows: Inability to Complete cycle 1 of therapy due to drug-related toxicity. > Grade 3 non-hematological drug-related toxicity (excluding alopecia) despite optimal supportive care Febrile neutropenia (absolute neutrophil count [ANC] <1,000/μL and fever >101° F (38.5° C)) Grade 4 neutropenia that occurs prior to day 21. (Grade 4 neutropenia that occurs after day 21 but resolves within 7 days of the scheduled cycle 2, will not be considered DLT) Platelet count < 25,000/μL Inability to initiate Cycle 2, Day 1 therapy within 7 days of scheduled start (i.e. cannot delay the start of Cycle 2 by more than 7 days following the normal 7 day recovery period) due to drug-related toxicity.

Outcome Time Frame:

6 months

Safety Issue:

Yes

Principal Investigator

Jeffrey Infante, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Sarah Cannon Research Institute

Authority:

United States: Food and Drug Administration

Study ID:

SCRI GI 105

NCT ID:

NCT00540579

Start Date:

November 2007

Completion Date:

January 2011

Related Keywords:

  • Pancreatic Cancer
  • Pancreas
  • Untreated
  • Advanced
  • Gemcitabine
  • CC-4047
  • Carcinoma
  • Pancreatic Neoplasms

Name

Location

University of Colorado Cancer Center Denver, Colorado  80262
Tennessee Oncology, PLLC Clarksville, Tennessee  37043