Submitted by: Jamie Anne Y. Lee 2017-05-18 00:00:00 Last Updated by: Jamie Anne Y. Lee 2018-04-25 16:13:04 Export to PDF

A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase 3 Study of Weekly Paclitaxel with or without Ramucirumab (IMC-1121B) in Patients with Advanced Gastric or Gastroesophageal Junction Adenocarcinoma, Refractory to or Progressive after First-Line Therapy with Platinum and Fluoropyrimidine

PHRR170523-001547

I4T-CR-JVCR

2017-CT0392

A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase 3 Study of Weekly Paclitaxel with or without Ramucirumab (IMC-1121B) in Patients with Advanced Gastric or Gastroesophageal Junction Adenocarcinoma, Refractory to or Progressive after First-Line Therapy with Platinum and Fluoropyrimidine

This is a multinational, randomized, multicenter, double-blind, placebo-controlled, Phase 3 study in patients with histologically or cytologically confirmed advanced gastric or GEJ adenocarcinoma, refractory to or progressive after first-line therapy with platinum and fluoropyrimidine. Approximately 450 patients will be randomized on a 2:1 ratio to Arm A (paclitaxel plus ramucirumab) and Arm B (paclitaxel plus placebo) to observe at least 336 deaths.

The primary objective of this study is to evaluate OS in patients treated with paclitaxel plus ramucirumab (IMC 1121B) versus paclitaxel plus placebo as second-line treatment in patients with advanced gastric or GEJ adenocarcinoma after failure of any platinum and fluoropyrimidine doublet with or without anthracycline (epirubicin or doxorubicin).
The secondary objectives of the study are to evaluate:
> PFS
> Time to progression
> Objective response rate
> Duration of objective response
> Safety profile
> Patient-reported outcome measures
In addition, exploratory objectives include:
> To explore biomarkers relevant to gastric or GEJ adenocarcinoma or safety, efficacy, and mechanism of
action of ramucirumab.

Regime Classification Priority
2010 - 2016 Health Technology Development Drug Discovery and Development
Start Date Duration in Months Target Completion Date Actual Completion Date
2018-01-09 27 2020-04-09 0000-00-00

Ongoing

Institution Classification Region LTO #
Eli Lilly and Company Private Business United States of America Not Applicable
Institution Classification Region LTO #
Quintiles Philippines, Inc. Private Business NCR CDRR-NCR-CRO-2
Institution Amount Region
Eli Lilly and Company N/A United States of America
Name E-Mail Phone Number Postal Address
Elena Lam QMNL.HealthRegistrymailbox@quintiles.com +6328585600 41F Unionbank Plaza Bldg., Meralco Ave., cor. Onyx Road, Ortigas Center, Pasig City, 1600
Name E-Mail Phone Number Postal Address
RuBing Han han_ru_bing@lilly.com +86 21 2302 0745 19F, Center T1 HKRI Taikoo, No. 288, Shimen 1 Road, Jingan District Shanghai, 200041, P.R. China
Name Expertise Affiliation
Maximino De Guzman Bello III, MD Medical Oncology St. Luke's Medical Center - Quezon City
Adonis Guancia, MD Medical Oncology Dr. Pablo O. Torre Memorial Hospital
Paul Dexter Santos, MD Medical Oncology De La Salle Health Sciences Institute
Ma. Noemi Alsay-Uy, MD Medical Oncology Cebu Doctors' University Hospital
Project Location Institutional Ethics Review Board
St. Luke's Medical Center - Quezon City St. Luke's Medical Center Institutional Ethics Review Committee
Dr. Pablo O. Torre Memorial Hospital Dr. Pablo O. Torre Memorial Hospital Research Ethics Review Committee
De La Salle Health Sciences Institute De La Salle Health Sciences Institute Independent Ethics Committee
Cebu Doctors' University Hospital Cebu Doctors' University Hospital - Institutional Ethics Review Committee

Advanced Gastric or Gastroesophageal Junction
Adenocarcinoma

The primary objective of this study is to evaluate OS in patients treated with paclitaxel plus ramucirumab (IMC 1121B) versus paclitaxel plus placebo as second-line treatment in patients with advanced gastric or GEJ adenocarcinoma after failure of any platinum and fluoropyrimidine doublet with or without anthracycline (epirubicin or doxorubicin).

The secondary objectives of the study are to evaluate:
> PFS
> Time to progression
> Objective response rate
> Duration of objective response
> Safety profile
> Patient-reported outcome measures
In addition, exploratory objectives include:
> To explore biomarkers relevant to gastric or GEJ adenocarcinoma or safety, efficacy, and mechanism of
action of ramucirumab.

Recruiting

  • China
  • Malaysia
  • Thailand

Clinical Trial

20170116164210

2017-04-10

Date Amendment Classification Reason
2017-07-07 Amendments related to the protocol
2017-09-25 Amendments related to the protocol
2017-10-03 Amendments related to the protocol Informed consent
2018-03-19 Amendments related to the protocol

Inclusion:
[1] Have provided signed informed consent prior to any study-specific procedures and are amenable to compliance with protocol schedules and testing.
[2] Are at least 18 years of age (or of an acceptable age according to local regulations, whichever is older) at the time of randomization.
[3] Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at study entry.
[4] Have a histopathologically or cytologically confirmed diagnosis of gastric or GEJ adenocarcinoma.
[5] Have metastatic disease or locally advanced, unresectable disease.
[6] Have at least 1 measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1. Positron emission tomography (PET) scans and ultrasounds may not be used for diagnostic purposes.
[7] Have experienced documented objective radiographic or symptomatic disease progression (for example, any new or worsening malignant effusion documented by ultrasound examination) which may be confirmed by pathologic criteria (histology and/or cytology) if appropriate, during first-line therapy, or within 4 months after the last dose of first-line therapy with any platinum/fluoropyrimidine doublet (acceptable prior platinum agents are cisplatin, carboplatin, or oxaliplatin; acceptable prior fluoropyrimidine agents are 5-fluorouracil, capecitabine, or S-1) with or without anthracycline (epirubicin or doxorubicin) for unresectable or metastatic disease.
[8] Have resolution to Grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03, of all clinically significant toxic effects of chemotherapy, surgery, radiotherapy, or hormonal therapy (with the exception of alopecia), except where otherwise noted in this eligibility criteria.
[9] Have adequate organ function, defined as:
> Total bilirubin ≤1.5 times (×) the upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3× ULN for AST/ALT if no liver metastases, ≤5× ULN if liver metastases.
> Serum creatinine ≤1.5× ULN or calculated creatinine clearance (CrCl; per the Cockcroft-Gault [1976] formula or equivalent and/or 24-hour urine collection) ≥50 mL/min (Cockcroft and Gault 1976).
> Absolute neutrophil count (ANC) ≥1.5× 109/L, hemoglobin ≥9 g/dL(5.58 mmol/L; packed red blood cell transfusions are not allowed within 1 week prior to baseline hematology profile), and platelets ≥100× 109/L.
> International Normalized Ratio (INR) ≤1.5 or prothrombin time ≤1.5× ULN.
> Partial thromboplastin time/activated partial thromboplastin time (PTT/aPTT) ≤1.5× ULN.
[10] Have urinary protein ≤1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥2+, then a 24-hour urine sample must be collected and must demonstrate [11] If female, are surgically sterile, postmenopausal, or compliant with a highly
effective contraceptive method (failure rate <1%) during and for 12 weeks
after the treatment period (oral hormonal contraception alone is not considered
highly effective and must be used in combination with a barrier method). If
male, are surgically sterile or compliant with a highly effective contraceptive
regimen during and for 6 months after the treatment period. The label (for
example, Summary of Product Characteristics, United States Package Insert,
and so on) requirements with regard to the methods and duration of
contraception during and after treatment with paclitaxel can differ between
countries. Country specific requirements will apply only if they are more
stringent than those already stipulated in the protocol.
[12] Have an estimated life expectancy of at least 12 weeks, in the judgment of the investigator.

Exclusion:
[13] Have squamous cell or undifferentiated gastric cancer.
[14] Have undergone major surgery within 28 days prior to randomization, or have had a central venous access device placement within 7 days prior to randomization.
[15] Have received any first-line chemotherapy other than platinum and fluoropyrimidine with or without anthracycline for advanced gastric or GEJ adenocarcinoma.
[16] Have received previous systemic chemotherapy with a cumulative dose of >900 mg/m2 of epirubicin or >400 mg/m2 of doxorubicin.
[17] Have received any previous systemic therapy (including investigational agents) targeting VEGF or the VEGFR signaling pathways. Other previous targeted therapies (for example, trastuzumab) are permitted, if stopped at least 28 days prior to randomization.
[18] Have a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered “significant”) during the 3 months prior to randomization.
[19] Are receiving therapeutic anticoagulation with warfarin, lowmolecular- weight heparin, or similar agents. Patients receiving prophylactic, low-dose anticoagulation therapy are eligible provided that the coagulation parameters defined in the inclusion criteria (INR ≤1.5) are met.
[20] Are receiving ongoing therapy with nonsteroidal anti-inflammatory agents (NSAIDs; for example, indomethacin, ibuprofen, naproxen, or similar agents) or other antiplatelet agents (for example, clopidogrel, ticlopidine, dipyridamole, and anagrelide). Aspirin (acetylsalicylic acid) at doses of ≤325 mg/day is permitted.
[21] Have significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to study entry.
[22] Have a history of GI perforation and/or fistulae within 6 months prior to randomization.
[23] Have symptomatic congestive heart failure (CHF; New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia.
[24] Have experienced any arterial thromboembolic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization.
[25] Have uncontrolled arterial hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg) despite standard medical management.
[26] Have a serious or nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to randomization.
[27] Have a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn’s disease, ulcerative colitis, or chronic diarrhea.
[28] Have a serious illness or medical condition(s) including, but not limited to the
following:
> Known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness
> Active or uncontrolled clinically serious infection
> Previous or concurrent malignancy, except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to the study
> Uncontrolled metabolic disorders or other nonmalignant organ or systemic diseases or secondary effects of cancer that induce a high medical risk and/or make assessment of survival uncertain
> Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient ineligible for entry into this study
> History or evidence of known central nervous system metastases or carcinomatous meningitis
> Child-Pugh B cirrhosis (or worse)
> Cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis
> Known allergy or hypersensitivity to mAb treatment or any components used in the ramucirumab drug product (DP) preparation
> Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy.
[29] Are pregnant or breastfeeding.
[30] Are currently enrolled in, or have been discontinued within the last 28 days
from, a clinical trial involving an investigational product or nonapproved use of a drug or device (other than the investigational drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Patients participating in surveys or observational studies are eligible to participate in this study.

Interventional

Ramucirumab (IMC-1121B, LY3009806)

Ramucirumab drug product (DP), injection for intravenous (IV) use, supplied in sterile, preservative-free, single-use vials containing 500 mg/50-mL product, at a final concentration of 10 mg/mL in a histidine-buffered formulation, administered as an IV infusion at a dose of 8 mg/kg on Days 1 and 15 of a 4-week cycle. The infusion should be delivered over approximately 60 minutes. The infusion rate should not exceed 25 mg/minute.
placebo to be administered will be calculated as if it were active product formulated at 10 mg/mL (at a volume equivalent to a dose of 8 mg/kg) on Days 1 and 15 of a 4 week cycle.
Paclitaxel, administered over approximately 60 minutes according to manufacturer standards, at a dose of 80 mg/m2 on Days 1, 8, and 15 of a 4-week cycle.

Randomized

Double Blind

Unspecified

Parallel

To evaluate OS in patients treated with paclitaxel plus ramucirumab (IMC 1121B) versus paclitaxel plus placebo as second-line treatment in patients with advanced gastric or GEJ adenocarcinoma after failure of any platinum and fluoropyrimidine doublet with or without anthracycline (epirubicin or doxorubicin).

Phase III

16

Unspecified

Unspecified

09 Jan 2018

Utilization Utilization Info
No records found.

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