Lapatinib With Carboplatin and Paclitaxel in Esophagus and Gastroesophageal Junction (GEJ)

NCT01395537 | Terminated Phase 1 Results DMC

• 1 other identifier: CASE2310
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Since lapatinib inhibits both EGFR and HER2 receptors, it is an attractive agent for the treatment of esophageal and GEJ tumors. PURPOSE: Lapatinib is currently approved for HER2 positive metastatic breast cancer in combination with capecitabine or letrozole. It is hoped that by giving lapatinib and carboplatin and paclitaxel together, their combined effects will further slow or stop the cancer cells from growing.

Conditions

Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction

Outcome Measures

Primary Outcomes (2)

• PHASE I: Number of Patients That Experience a Grade 3-4 Dose Limiting Toxicity

  A dose limiting toxicity (DLT) will be defined as any grade 3-4 non-hematologic toxicity or increase in bilirubin \>/= 2 mg/dL (\>2X baseline in patients with Gilbert's syndrome), or elevation in AST/ALT \> 3.0 X ULN during the first 3 week course of therapy.

  after 9 weeks (3 cycles) of treatment

• PHASE II: To Assess the Response Rate to This Regimen.

  Number of patients with stable or responding disease after 6 cycles of carboplatin and paclitaxel will continue treatment with lapatinib alone until progression of disease or intolerable side effects.

  after 37 months

Secondary Outcomes (1)

• To Determine the Overall Survival

  after 37 months

Study Arms (1)

Lapatinib With Carboplatin and Paclitaxel

EXPERIMENTAL

Drug: Carboplatin AUC; Drug: Paclitaxel; Drug: lapatinib

Interventions

Carboplatin AUC DRUG

Carboplatin AUC 6 IV over 30 minutes on day one of a three week cycle. This will be continued for 6 cycles or until progression of disease or intolerable side effects.

Lapatinib With Carboplatin and Paclitaxel

Paclitaxel DRUG

Paclitaxel 175 mg/m2 IV over 3 hours day one of a three week cycle. This will be continued for 6 cycles or until progression of disease or intolerable side effects.

Lapatinib With Carboplatin and Paclitaxel

lapatinib DRUG

Lapatinib should be taken once daily, at the same time daily, on an empty stomach, either 1 hour before, or 1 hour after meals.

Lapatinib With Carboplatin and Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologic diagnosis of adenocarcinoma of the esophagus, or gastroesophageal junction based on biopsy material or adequate cytologic exam.
• Patients must have incurable metastatic or recurrent adenocarcinoma of esophagus or gastroesophageal junction.
• Patients must have an ECOG performance status of 0-1.
• Patients must have adequate bone marrow function as evidence by: absolute neutrophil count \> 1500/uL, and platelet count \> 100,000/uL
• Patients must have adequate renal function as evidenced by a Cockcroft-Gault calculated creatinine clearance \> 30 mL/min.
• Patient must have adequate hepatic function as evidenced by: serum total bilirubin \< 2.0 mg/dl, and AST/ALT \< 3 X the institutional upper limit of normal. Patients with an elevated unconjugated bilirubin (Gilbert's syndrome) will be eligible if hepatic enzymes and function are otherwise completely normal (AST/ALT/Alk Phos within normal limits), and there is no evidence of hemolysis.
• Patients must have cardiac ejection fraction \> 50% as measured by echocardiogram or MUGA scan.
• Patient must agree to stop medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of lapatinib. (See Appendix I).
• Patients must be able to adhere to the study visit schedule and other protocol requirements.
• Patients must have measurable/evaluable disease as per RECIST 1.1 criteria.
• Tumor must be tested for HER2 and EGFR before patient registration.
• Patients of childbearing potential must agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication (an effective form of contraception is an oral contraceptive or a double barrier method).
• Patients must be \>18 years old.
• Women of childbearing potential must have a negative pregnancy test prior to enrollment.
• Patients must have a life expectancy \>12 weeks.

You may not qualify if:

• Patients with any other diagnosis except for adenocarcinoma (squamous cell carcinoma, small cell carcinoma, lymphoma, etc) will be ineligible.
• Patients with another active malignancy within the last 5 years will not be eligible except for curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with PSA \<1.0 mg/dL on 2 successive evaluations at least 3 months apart, with the most recent evaluation within 4 weeks of entry.
• Patients may not have had any previous chemotherapy for recurrent or metastatic disease and no chemotherapy or radiation therapy within the past 4 weeks.
• Patients may not have received any previous treatment with carboplatin, paclitaxel, or a HER2 or EGFR inhibitor prior to enrollment.
• Patients may not be receiving any other investigational agents or other concurrent anticancer therapy.
• Patients with brain metastases are excluded.
• Patients with \> grade 2 peripheral neuropathy per NCI's Common Toxicity Criteria Version 4.0 will be ineligible.
• Males with QTc \> 450 or females with QTc \> 470msec will be ineligible.
• Patients with active cardiac disease are excluded including current uncontrolled or symptomatic angina, history of clinically significant arrhythmias requiring medications, (with the exception of asymptomatic atrial tachycardias requiring anticoagulation and/or beta-blockade), myocardial infarction \< 6 months from study entry, uncontrolled or symptomatic congestive heart failure, or any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
• Women who are currently pregnant or lactating will be ineligible.
• Any other uncontrolled inter-current medical or psychiatric illness.
• Known HIV-positive patients will be excluded.
• Patients with any gastrointestinal disease resulting in an inability to take oral )or feeding-tube administered medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, or uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis).
• Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (2)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44016, United States

Location

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

Paclitaxel; Lapatinib

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

One patient was treated in phase II cohort. The study was then prematurely terminated because of the results of the TRIO-013/LOGiC trial. It failed to meet its primary survival endpoint, suggesting little justification for continuation of our study.

Results Point of Contact

• Title: David Adelstein MD
• Organization: Case Comprehensive Cancer Center

adelstd@ccf.org

216-444-9310

Study Officials

• David Adelstein, MD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• Neelesh Sharma, MD

  Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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 12, 2011
• First Posted: July 15, 2011
• Study Start: August 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: March 19, 2019
• Results First Posted: February 26, 2019

Record last verified: 2019-03

Locations

US (2)