Lenalidomide and Paclitaxel in Advanced Solid Tumors

NCT01155505 | Unknown Phase 1

• 1 other identifier: S095LEPT01
• Study Type: interventional
• Target: 28
• Locations: 2 countries
• Sites: 2

Brief Summary

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. 1.Define the safety profile of the CC-5013 and paclitaxel given in combination
2. 2.Define the pharmacokinetics of CC-5013 and paclitaxel given in combination
3. 3.Define the pharmacodynamic effects of the combination by monitoring potential biomarkers of the different biological activities of each component of the regimen
4. 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. 5.Collect evidence of antitumor activity in selected tumor types

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Define the MTD of the combination of CC-5013 and paclitaxel in patients with advanced solid tumors

  Number of Dose-Limiting Toxicities (DLTs)

  4 weeks after the first drug administration

Secondary Outcomes (4)

• Safety profile of the drug combination

  from the first administration to 30 days after the trial end

• Pharmacokinetics of CC-5013 and paclitaxel given in combination

  untill 4 weeks after the first drug administration

• the pharmacodynamic effects of CC-5013 and paclitaxel given in combination

  from the first drug administration to 30 days after trial end

• Evidence of antitumor activity in selected tumor types

  From the first drug administration to 30 days after the trial end

Study Arms (1)

CC-5013 in combination with Paclitaxel

EXPERIMENTAL

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)

Interventions

Lenalidomide (CC-5013) DRUG

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

CC-5013 in combination with Paclitaxel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Southern Europe New Drug Organization: lead
• Celgene Corporation: collaborator

Study Sites (2)

Fondazione IRCSS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Istituto Oncologico della Svizzera Italiana

Bellinzona, 6500, Switzerland

Location

MeSH Terms

Interventions

Lenalidomide

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Cristiana Sessa, MD

  Istituto Oncologico della Svizzera Italiana -6500 Bellinzona, Switzerland

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2010
• First Posted: July 1, 2010
• Study Start: November 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: March 1, 2012
• Last Updated: September 13, 2011

Record last verified: 2011-09

Locations

IT (1); CH (1)