Lenalidomide and Paclitaxel in Advanced Solid Tumors

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2011 by Southern Europe New Drug Organization.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Southern Europe New Drug Organization
ClinicalTrials.gov Identifier:
NCT01155505
First received: June 30, 2010
Last updated: September 12, 2011
Last verified: September 2011
  Purpose

This is a dose finding, open-label, uncontrolled, dose-escalation trial to determine the maximum Tolerated Dose (MTD) of the combination of CC-5013 (Lenalidomide)and paclitaxel in patients with advanced solid tumors.

Other purposes of the study are:

  1. Define the safety profile of the CC-5013 and paclitaxel given in combination
  2. Define the pharmacokinetics of CC-5013 and paclitaxel given in combination
  3. Define the pharmacodynamic effects of the combination by monitoring potential biomarkers of the different biological activities of each component of the regimen
  4. Define the optimal biological dose (OBD) and the dose recommended (RD) for phase II studies in selected tumor types (breast, ovary, prostate, NSCLC)
  5. Collect evidence of antitumor activity in selected tumor types

Condition Intervention Phase
Advanced Solid Tumors
Drug: Lenalidomide (CC-5013)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase Ib of CC-5013 and Paclitaxel in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Southern Europe New Drug Organization:

Primary Outcome Measures:
  • Define the MTD of the combination of CC-5013 and paclitaxel in patients with advanced solid tumors [ Time Frame: 4 weeks after the first drug administration ] [ Designated as safety issue: Yes ]
    Number of Dose-Limiting Toxicities (DLTs)


Secondary Outcome Measures:
  • Safety profile of the drug combination [ Time Frame: from the first administration to 30 days after the trial end ] [ Designated as safety issue: Yes ]
    Physical examination, laboratory and instrumental assessments and AE type and frequency

  • Pharmacokinetics of CC-5013 and paclitaxel given in combination [ Time Frame: untill 4 weeks after the first drug administration ] [ Designated as safety issue: Yes ]
    CC-5013 and paclitaxel plasma concentration

  • the pharmacodynamic effects of CC-5013 and paclitaxel given in combination [ Time Frame: from the first drug administration to 30 days after trial end ] [ Designated as safety issue: No ]

    Increase (%) in selected serum cytokines (IL2, IL6, IL10, IL12, TNFα, γIF and TGFβ).

    T-cell phenotyping:

    • T-cell markers (CD4/CD45RA/CCR7/CD3,CD8/CD45RA/CCR7/CD3)
    • Treg markers: CD4/CD25/FoxP3
    • NKcells: CD16+/CD56+

  • Evidence of antitumor activity in selected tumor types [ Time Frame: From the first drug administration to 30 days after the trial end ] [ Designated as safety issue: No ]
    Response Rate according to RECIST criteria


Estimated Enrollment: 28
Study Start Date: November 2009
Estimated Study Completion Date: March 2012
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CC-5013 in combination with Paclitaxel

Cohorts of 3 evaluable patients will initially be entered within each dose level, sequentially. In each dose level the second and third patient will enter 2 weeks after the first one. The second and third patient may be treated simultaneously, except if a DLT is reported in the first patient, in which case the second and third patient should be treated sequentially, at least one week apart.

Dose escalation will be done when all the patients included in each DL will finish the first treatment cycle. Three additional patients will be sequentially entered (separated by one week each other) if one DLT is observed in cycle 1 among the first 3 patients entered within a dose level. If a DLT is observed in a second patient at this dose level, no further dose escalation will be allowed and the dose level will be considered the MTD.

Once the RD (one level below the MTD) has been defined, additional patients (up to 12) will be treated in order to confirm the safety profile of the combination.

Drug: Lenalidomide (CC-5013)
CC-5013 given PO daily on D1-D14 every 21 days and Paclitaxel administered IV over 1 hour on d1 and 8 every 21 days until tumor progression or unacceptable toxicity

Detailed Description:

The new immunomodulatory drugs (IMiD) derivatives of thalidomide (CC-5013 lenalidomide and CC4047 pomalidomide) are endowed of direct antitumor activity besides the indirect effects attributed to antiangiogenic, antiinflammatory and T-cell co-stimulatory properties.

Combination therapy with cytotoxic agents or other anticancer drugs could lead to additive or synergistic interactions and support their clinical development in tumor types in which the specific activities of IMiDs could be of potential value.

Combinations with weekly paclitaxel could be of interest because of its antiangiogenic activity, antitumor activity in prostate, NSCLC, ovary, breast cancer, tumor types in which IMiD could be of clinical value because of either enhancement of tumor specific immunity (ovary, prostate) or inhibition of Treg function (breast, NSCLC, ovary).

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histological/cytological diagnosis of solid tumors for which a treatment with paclitaxel could be indicated (preferentially ovary, breast, prostate, NSCLC)
  • Documented progression of the tumor in the 3 months preceding the study
  • Expected survival ≥ 3 months
  • Age 18-75 years
  • ECOG PS 0-1
  • measurable/evaluable disease during escalation phase, according to modified RECIST criteria. For patients with ovarian and prostatic cancer, tumor markers (CA125 for ovarian and PSA for prostatic) are accepted as only evidence. Measurable/evaluable disease is mandatory during the RD expansion phase

    •≤ 2 prior lines of chemotherapy for metastatic disease. For ovarian patients reintroduction of a platinum at relapse, after an initial response lasting > 6 months is considered one chemotherapy regimen only

  • Adequate contraception for all fertile patients
  • Adequate hematological function as defined by: ANC ≥ 1.5 x 109/L, platelet count ≥100 x 109/L, hemoglobin ≥ 10 g/dL.
  • Normal PTand INR; fibrinogen > lower Normal Limit (LNL)
  • Adequate renal function, as defined by: creatinine ≤ 1.5 x UNL
  • Adequate hepatobiliary function, as defined by the following baseline liver function tests:

    • total serum bilirubin within upper normal limit (UNL)
    • alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤2.5xUNL or ≤ 5xUNL in case of liver metastases; alkaline phosphatase (AP) ≤ 2.5xUNL. If total alkaline phosphatase (AP) > 2.5xUNL, alkaline phosphatase liver fraction must be ≤ 2.5xUNL.
    • albumin ≥ 2.5 g/dL

Exclusion Criteria:

  • History of DVT or coagulation disturbances
  • Need of treatment with oral anticoagulants or LMW heparin
  • Clinical resistance to taxanes defined as progression during therapy or within 6 months from the end of adjuvant treatment
  • Known or prior hypersensitivity to taxanes or drugs containing chemophor, or to thalidomide (or analogues)
  • Preexisting peripheral neuropathy > grade 1
  • Concomitant treatment with non steroid anti-inflammatory agents (NSAIA), high dose steroids or immunosuppressants
  • Concomitant hormonal treatment (including those with antiandrogenic)
  • Radiotherapy involving > 30% of the active bone marrow
  • Radiotherapy ≤ 4 weeks prior to enrolment
  • Other chemotherapy treatment ≤ 4 weeks prior to enrolment, at least 6 weeks for nitrosoureas or mitomycin C, or investigational drugs
  • Symptomatic brain metastases
  • Active infection
  • Gastro-intestinal abnormalities, inability to take oral medication, any condition affecting absorption
  • Impaired cardiac function including any of the following:

History of cardiac disease, such as myocardial infarction, in the year prior to enrollment in the clinical trial, symptomatic/uncontrolled angina pectoris, congestive heart failure or uncontrolled cardiac ischemia, or arrhythmia, abnormal left ventricular ejection fraction, or uncontrolled arterial hypertension.

  • Major surgery in the two weeks prior to entering the clinical trial
  • Concurrent treatment with any other anti-cancer therapy
  • History of another neoplastic disease (except basal cell carcinoma of the skin or uterine cervix carcinoma in situ adequately treated), unless in remission for ≥ 5 years
  • Patient unable to comply with the study protocol owing to psychological, social or geographical reasons
  • Pregnant and lactating women
  • Men and women of childbearing potential who are not using an effective method of contraception
  • Participation in another clinical trial or treatment with any investigational product within 30 days prior to inclusion in this study
  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: NCT01155505

Locations
Italy
Fondazione IRCSS Istituto Nazionale dei Tumori
Milan, Italy, 20133
Switzerland
Istituto Oncologico della Svizzera Italiana
Bellinzona, Switzerland, 6500
Sponsors and Collaborators
Southern Europe New Drug Organization
Celgene Corporation
Investigators
Study Chair: Cristiana Sessa, MD Istituto Oncologico della Svizzera Italiana -6500 Bellinzona, Switzerland
  More Information

No publications provided

Responsible Party: Southern Europe New Drug Organization
ClinicalTrials.gov Identifier: NCT01155505     History of Changes
Other Study ID Numbers: S095LEPT01
Study First Received: June 30, 2010
Last Updated: September 12, 2011
Health Authority: Italy: Ethics Committee
Italy: The Italian Medicines Agency
Switzerland: Ethikkommission
Switzerland: Swissmedic

Additional relevant MeSH terms:
Neoplasms
Paclitaxel
Lenalidomide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014