Lenalidomide and Paclitaxel in Advanced Solid Tumors

Advanced Solid Tumors Clinical Trial

Official title:

Phase Ib of CC-5013 and Paclitaxel in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01155505
• Other study ID #: S095LEPT01
• Status: Active, not recruiting
• Phase: Phase 1
• First received: June 30, 2010
• Last updated: September 12, 2011
• Start date: November 2009
• Est. completion date: March 2012

Study information

• Verified date: September 2011
• Source: Southern Europe New Drug Organization
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics CommitteeItaly: The Italian Medicines AgencySwitzerland: EthikkommissionSwitzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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. 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

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 28
• Est. completion date: March 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

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

Locations

Country	Name	City	State
Italy	Fondazione IRCSS Istituto Nazionale dei Tumori	Milan
Switzerland	Istituto Oncologico della Svizzera Italiana	Bellinzona

Sponsors (2)

Lead Sponsor	Collaborator
Southern Europe New Drug Organization	Celgene Corporation

Countries where clinical trial is conducted

Italy,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Safety profile of the drug combination	Physical examination, laboratory and instrumental assessments and AE type and frequency	from the first administration to 30 days after the trial end	Yes
Secondary	Pharmacokinetics of CC-5013 and paclitaxel given in combination	CC-5013 and paclitaxel plasma concentration	untill 4 weeks after the first drug administration	Yes
Secondary	the pharmacodynamic effects of CC-5013 and paclitaxel given in combination	Increase (%) in selected serum cytokines (IL2, IL6, IL10, IL12, TNFa, ?IF and TGFß).; T-cell phenotyping: T-cell markers (CD4/CD45RA/CCR7/CD3,CD8/CD45RA/CCR7/CD3); Treg markers: CD4/CD25/FoxP3; NKcells: CD16+/CD56+	from the first drug administration to 30 days after trial end	No
Secondary	Evidence of antitumor activity in selected tumor types	Response Rate according to RECIST criteria	From the first drug administration to 30 days after the trial end	No