Phase 2
Completed N=40
A Study of Ramucirumab (IMC-1121B) and Paclitaxel in Participants With Solid Tumors
Malignant Solid Tumor
Source: ClinicalTrials.gov NCT01515306 ↗
Enrolled (actual)
40
Serious AEs
17.1%
Results posted
Jun 2014
Primary outcomePrimary: Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Paclitaxel From Time Zero to Infinity [AUC(0-∞)] in Cycle 1 — 29 nanograms*hour/milliliter/milligram
Summary
The purpose of this study is to investigate whether there are no clinically significant pharmacokinetic effects of concomitant ramucirumab (IMC-1121B) on paclitaxel by investigating the pharmacokinetics (PK) of each in participants with advanced malignant solid tumors.
Part A of this study will investigate the potential of concomitant ramucirumab (IMC-1121B) to affect the pharmacokinetics of paclitaxel. Part B of this study will investigate the pharmacokinetics of ramucirumab (IMC-1121B) as monotherapy.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Paclitaxel From Time Zero to Infinity [AUC(0-∞)] in Cycle 1 |
29 | — |
| PRIMARY Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Paclitaxel From Time Zero to Infinity [AUC(0-∞)] in Cycle 2 |
31.67 | — |
| PRIMARY Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Paclitaxel in Cycle 1 |
18.84 | — |
| PRIMARY Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Paclitaxel in Cycle 2 |
18.30 | — |
| PRIMARY Part B: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] as Monotherapy |
55.3 | — |
| SECONDARY Part A: Pharmacokinetics - Dose-Normalized Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] in the Presence of Paclitaxel |
55.4 | — |
| SECONDARY Part A: Pharmacokinetics - Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Ramucirumab in the Presence of Paclitaxel |
0.384 | — |
| SECONDARY Part A: Immunogenicity of Ramucirumab in Combination With Paclitaxel - Number of Participants With Anti-Ramucirumab Antibodies |
— | — |
| SECONDARY Part B: Immunogenicity of Ramucirumab as Monotherapy - Number of Participants With Anti-Ramucirumab Antibodies |
— | — |
Eligibility Criteria
Inclusion Criteria
- Has histologic or cytologic documentation of a malignant solid tumor
- Has an advanced solid tumor that is refractory to standard therapy or for which no standard therapy is available
- Part A only: Has had 0-1 prior taxane-containing treatment regimens (including taxane monotherapy), which must have been completed at least 6 months before the first dose of study medication (prior bevacizumab is allowed)
- Part B only: Prior bevacizumab- and taxane-containing treatment regimens (including taxane monotherapy) are allowed, provided these regimens have been completed at least 6 months before the first dose of study medication
- Has resolution to Grade ≤ 1 of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy with the exception of peripheral neuropathy, which must not have exceeded Grade 1, by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v 4.0)
- Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 - 2
- Has adequate hematologic function. Blood transfusion is allowed but must be completed 48 hours before study drug administration
- Has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal [ULN], aspartate transaminase [AST] and alanine transaminase [ALT] ≤ 1.5 x ULN
- Has serum creatinine ≤ 1.5 x ULN. If serum creatinine > 1.5 x ULN, the calculated creatinine clearance (CrCl) should be ≥ 40 milliliter/minute (mL/min)
- Urinary protein is <2+ on dipstick or routine urinalysis (UA)
- Must have adequate coagulation function as defined by an international normalized ratio (INR) of ≤ 1.5 and a partial thromboplastin time (PTT) or an activated PTT (aPTT) ≤ 1.5 x ULN
- Eligible participants of reproductive potential agree to use adequate method of contraception during the study period and for 12 weeks after the last dose of study medication
Exclusion Criteria
- Is receiving concomitant therapy with clinically relevant inhibitors or inducers of cytochrome P450, CYP2C8, CYP3AY and/or isoenzymes
- Are currently enrolled in, or discontinued within the last 14 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
- Has received a monoclonal antibody within 42 days prior to first dose of study medication
- Has received radiotherapy within 14 days prior to first dose of study medication
- Has received cytotoxic chemotherapy within 21 days (6 weeks for nitrosoureas or mitomycin C) prior to first dose of study medication
- Has a cardiac left ventricular ejection fraction (LVEF) not within institutional limits of normal on a multigated acquisition scan (MUGA) or echocardiogram
- Is receiving concurrent treatment with another anticancer therapy, including chemotherapy, immunotherapy, hormonal therapy, radiation therapy, chemoembolization, targeted or other investigational anticancer therapy
- Is receiving chronic therapy with nonsteroidal anti-inflammatory agents or other antiplatelet agents. Aspirin use at doses up to 325 milligrams/day (mg/day) and analgesic agents with no or low bleeding risk are permitted
- Has a history of uncontrolled hereditary or acquired bleeding or thromboembolic disorders
- Has experienced any arterial thromboembolic event, including myocardial infarction (MI), unstable angina stroke or transient ischemic attack (TIA), within 6 months prior to first dose of study medication
- Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the 3 months prior to first dose of study medication
- Has experienced a Grade 3 or 4 hemorrhagic event within 3 months prior to first dose of study medication
- Has experienced peripheral neuropathy ≥ Grade 2 at any time prior to study entry
- Has a bowel obstruction, history or pr
Data sourced from ClinicalTrials.gov (NCT01515306). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.