Lenalidomide and Paclitaxel in Prostate Cancer

NCT00933426 | Terminated Phase 1

• 2 other identifiers: 2008-0606NCI-2010-01039
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of the Phase I part of this clinical research study is to find the highest tolerable dose of Revlimid® (lenalidomide) that can be given in combination with paclitaxel to patients with prostate cancer who have failed treatment with taxanes. The goal of the Phase II part of this clinical research study is to learn if lenalidomide and paclitaxel can help to control prostate cancer. The safety of this combination treatment will be studied in both phases of the study. UPDATE: Study was terminated early due to slow accrual as a Phase I dose escalation study, without progression to Phase II study portion.

Conditions

Prostate Cancer

Keywords

Castration-Resistant Prostate Cancer; CRPC; Prostate; Lenalidomide; Revlimid; CC-5103; Paclitaxel; Taxol; Taxanes

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of Lenalidomide in Combination with Low-Dose Weekly Paclitaxel

  MTD defined as dose with posterior mean Pr{toxicity} closest to .33 at the end of the trial, provided that it is not terminated early. The CRM will be implemented using fixed toxicity probabilities (p1, p2, p3, p4, p5) = (.05, .20, .33, .45, .60) under the model Pr{toxicity \| dose level j} = {pj}exp(a) , where a follows a normal prior with mean 0 and variance 2. Dose limiting toxicity (DLT) defined as any of the following treatment-related events occurring within two cycles of therapy (i) uncontrolled or intolerable grade 2 non-hematologic toxicity \> 7 days, (ii) grade 3or 4 nausea/vomiting/diarrhea \> 48 hours, (iii) \> grade 3 fatigue \> 7 days and any other grade 3or 4 non-hematologic toxicity; (iv) grade 4 hematologic toxicity (v) neutropenic fever defined as absolute neutrophil count (ANC) \< 1000 and temperature \>/ 101 degrees F; (vi) any other regimen-related adverse event that precludes delivery of the first two cycles of therapy.

  After 2, 28 day cycles

Secondary Outcomes (1)

• Progression-Free (PFS) Time in Patients with a Lymph Node Dominant Clinical Phenotype

  After 2, 28 day cycles

Study Arms (1)

Lenalidomide and Paclitaxel

EXPERIMENTAL

Phase I: Up to 5 differing doses of Lenalidomide tested plus fixed dose of Paclitaxel. Phase II: Lenalidomide at highest tolerated dose from Phase I plus Paclitaxel.

Drug: Lenalidomide; Drug: Paclitaxel

Interventions

Lenalidomide DRUG

Lead-In beginning dose of 5 mg capsules by mouth once a day for 21 days in a row, followed by 7 days of rest (Days 22-28) for a 28 day cycle.

Also known as: Revlimid, CC-5013

Lenalidomide and Paclitaxel

Paclitaxel DRUG

50 mg/m\^2 given by vein over 1 hour on Days 1, 8, and 15 of each 28 day cycle.

Also known as: Taxol

Lenalidomide and Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Patients with metastatic adenocarcinoma of the prostate
• Patients in Phase II must have radiographic evidence of multiple (\>/= 2) or bulky (\>/= 5cm diameter) lymph node metastases with \< 2 bone (on radionuclide bone scan) discrete sites of involvement.
• Patient must have had front-line chemotherapy for castrate-resistant metastatic disease. Any number of prior chemotherapy regimens is permitted, except within the last 3 weeks. No prior thalidomide or lenalidomide therapy is permitted.
• Patients must have evidence of progression of disease based on any one of the following criteria: a) PSA- progression is defined as 2 consecutive increments in PSA (with an absolute change of at least 1ng/mL) over 4 weeks. b) An increase by 25% of the product of bi-dimensional disease or 30% in maximum diameter or appearance of an unequivocally new lesion qualifies as progression. c) Worsening symptoms clearly attributable to disease progression qualifies as progression e.g. worsening malignant bony pain.
• Patients on antiandrogens should be discontinued from flutamide, nilutamide or cyproterone acetate for at least 4 weeks and bicalutamide for 6 weeks. If progression is documented during or after this time interval, patients are eligible. Patients who have not had response to deferred (secondary) therapy with antiandrogens do not have to satisfy this waiting period prior to enrollment.
• Patients must have a performance status of \</= 2 (ECOG).
• Patients will not receive any concurrent biological, immunological, second-line hormonal therapy or chemotherapy. Patients receiving replacement or therapeutic doses of corticosteroid for non-malignant disease while disease progression was established may continue on such therapy.
• Patients must have recovered from prior chemotherapy, biological or immunological therapy or radiation delivered within the last 28 days. Radioisotope therapy with strontium delivered within the last 90 days or samarium within the last 60 days is not permitted.
• Patients must have a castrate serum testosterone level (\</= 50ng/ml) documented in the last six weeks. For patients who are medically castrated, luteinizing hormone releasing hormone analog must continue to maintain testicular suppression.
• Patients must have adequate bone marrow function defined as an absolute peripheral granulocyte count of \>/= 1,500/mm\^3 and platelet count of \>/= 75,000/mm\^3.
• Patients must have adequate hepatic function defined with a bilirubin of \</= 2 X upper limits of normal and AST/ALT \</= 2.5 X the upper limits of normal.
• Patients must have adequate renal function defined as creatinine clearance \>/= 40 cc/min (measured or calculated by Cockcroft and Gault formula).
• Must be fully recovered from any previous surgery, in terms of wound healing.
• Patients must sign an informed consent indicating that they are aware of the investigational nature of this study, in keeping with the policies of the institution.
• All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.

You may not qualify if:

• Patients with severe or uncontrolled infection defined as symptomatic and/or requiring intravenous antibiotics.
• Patients with small cell or sarcomatoid variant of prostate cancer.
• Patients with symptomatic congestive heart failure (CHF), pulmonary embolus, vascular thrombosis, transient ischemic attack, cerebrovascular accident, unstable angina or MI in the last 3 months or evidence of active myocardial ischemia by symptoms or electrocardiogram (ECG).
• Known severe hypersensitivity to taxanes.
• Patients with central nervous system (CNS) metastasis or cord compression are excluded except those patients that have had complete excision or radiotherapy and remain asymptomatic for at least 2 months.
• Oxygen-dependent lung disease or \>/= grade 2 peripheral neuropathy.
• Known intolerance of corticosteroid therapy that would preclude its use as premedication for paclitaxel.
• Uncontrolled severe hypertension or uncontrolled diabetes mellitus.
• Active second malignancies. Non-threatening second malignancies such as superficial low-grade transitional cell carcinoma of the bladder or Rai Stage 0 chronic lymphocytic leukemia or stable small renal cell carcinomas may be exempt from such stipulation at the discretion of the Principal Investigator.
• Overt psychosis or mental disability or otherwise incompetent to give informed consent. Patients who are unwilling or unable to comply with the RevAssist® program or with a history of non-compliance with medical regimens or who are considered potentially unreliable.
• Patients with known HIV or active hepatitis A, B, or C infection.
• Patients receiving any concurrent biological, immunological, second-line hormonal therapy or chemotherapy. Patients receiving replacement or therapeutic doses of corticosteroid for non-malignant disease while disease progression was established may continue on such therapy.
• Patients who have not recovered from prior chemotherapy, biological or immunological therapy or radiation delivered within the last 28 days. Radioisotope therapy with strontium delivered within the last 90 days or samarium within the last 60 days is not permitted.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Celgene Corporation: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Lenalidomide; Paclitaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

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; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Lance Pagliaro, MD

  M.D. Anderson Cancer Center

  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: July 3, 2009
• First Posted: July 7, 2009
• Study Start: August 1, 2009
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: October 26, 2016

Record last verified: 2016-10

Locations

US (1)