Lenalidomide and Paclitaxel in Advanced Solid Tumors
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:
- Define the safety profile of the CC-5013 and paclitaxel given in combination
- Define the pharmacokinetics of CC-5013 and paclitaxel given in combination
- Define the pharmacodynamic effects of the combination by monitoring potential biomarkers of the different biological activities of each component of the regimen
- Define the optimal biological dose (OBD) and the dose recommended (RD) for phase II studies in selected tumor types (breast, ovary, prostate, NSCLC)
- Collect evidence of antitumor activity in selected tumor types
|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|
- 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)
- 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 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
|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)|
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
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).
|Fondazione IRCSS Istituto Nazionale dei Tumori|
|Milan, Italy, 20133|
|Istituto Oncologico della Svizzera Italiana|
|Bellinzona, Switzerland, 6500|
|Study Chair:||Cristiana Sessa, MD||Istituto Oncologico della Svizzera Italiana -6500 Bellinzona, Switzerland|