CC-4047 With Gemcitabine for Untreated Advanced Carcinoma of the Pancreas

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT00540579
First received: October 5, 2007
Last updated: February 8, 2013
Last verified: February 2013
  Purpose

Because the activity of CC-4047 addresses numerous mechanisms of carcinoma growth inhibition - including, but not limited to anti-angiogenesis - CC-4047 has been selected for development as part of induction chemotherapy regimens for solid tumors. This study in pancreatic cancer is designed to determine the appropriate CC-4047 dose and regimen in combination with gemcitabine.


Condition Intervention Phase
Pancreatic Cancer
Drug: Pomalidomide
Drug: Gemcitabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of CC-4047 in Combination With Gemcitabine in Subjects With Untreated Advanced Carcinoma of the Pancreas

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Determination of Maximum Tolerated Dose (MTD), The Dose of Study Drug(s) Which Causes <33% of Patients Treated to Experience Unacceptable Side Effects [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

    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.

  • The Safety and Tolerability of Protocol Treatment, Defined as the Percentage of Patients Experiencing Severe or Life-threatening Side Effects Per CTCAE Version 3.0 [ Time Frame: 24 Months ] [ Designated as safety issue: Yes ]
    The relative incidence of Grade 3/4 adverse events from protocol treatment as defined by Common Terminology Criteria for Adverse Events v3.0 (CTCAE)


Enrollment: 23
Study Start Date: November 2007
Study Completion Date: January 2011
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intervention
All patients received gemcitabine 1000 mg/m2 IV on days 1, 8, and 15 of a 28 day cycle. Pomalidomide was administered orally on days 1-21 at doses escalated from 2 mg to 10 mg daily.
Drug: Pomalidomide
Phase 1: Subjects will be enrolled in dose-escalating cohorts to be treated with CC-4047 on days 1-21 Phase II: Subjects will be enrolled to receive oral CC-4047 at the MTD days 1 - 21
Other Name: CC-4047
Drug: Gemcitabine
1000 mg/m2 IV on days 1, 8, and 15 of 28 day cycle
Other Name: Gemzar

Detailed Description:

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.

  Eligibility

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

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.
  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: NCT00540579

Locations
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
United States, Tennessee
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37023
Sponsors and Collaborators
SCRI Development Innovations, LLC
Celgene Corporation
Investigators
Study Chair: Jeffrey Infante, M.D. SCRI Development Innovations, LLC
  More Information

Publications:
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00540579     History of Changes
Other Study ID Numbers: SCRI GI 105, PO-PANC-PI-009
Study First Received: October 5, 2007
Results First Received: February 8, 2013
Last Updated: February 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Pancreas
Untreated
Advanced
Gemcitabine
CC-4047

Additional relevant MeSH terms:
Carcinoma
Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Pancreatin
Pancrelipase
Gemcitabine
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on July 22, 2014