Adenocarcinoma of the EsophagusPhase 1/2NCT01395537

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

A Phase 1/2 study testing Carboplatin AUC, Paclitaxel and lapatinib in people with Adenocarcinoma of the Esophagus and Adenocarcinoma of the Gastroesophageal Junction, run by Case Comprehensive Cancer Center at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Adenocarcinoma of the Esophagus, Adenocarcinoma of the Gastroesophageal Junction
What is being tested?: Carboplatin AUC, Paclitaxel and lapatinib
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 2 sitesUnited States
Study dates: Aug 2011to Dec 2014
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Show all 16Show fewer

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.
Patients must be able to tolerate oral (or feeding-tube administered) medications.

Who cannot join

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.

Show all 14Show fewer

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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44016
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106

Other trials in United States

About this study

Official title: Phase I/II Pilot Study of Lapatinib in Combination With Carboplatin and Paclitaxel in the Treatment of Recurrent/Metastatic Adenocarcinoma of the Esophagus and Gastroesophageal Junction (GEJ)

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.

Read the detailed description

OBJECTIVES:

Phase I: To assess the toxicity and feasibility of the addition of lapatinib to carboplatin and paclitaxel in patients with recurrent/metastatic adenocarcinoma of the esophagus and gastroesophageal junction.
Phase II: To assess the response rate to this regimen.

OUTLINE:

There will be an initial phase I safety cohort studies requiring up to 12 patients, followed by a phase II cohort using the lapatinib dose defined in phase I. Carboplatin and paclitaxel doses will not be escalated. The initial dose of lapatinib of 750 mg daily by mouth will be given to 6 patients. There will be no dose escalation of the lapatinib above 1000 mg daily. The lapatinib dose for the phase II cohort of this trial will be based only on toxicities experienced during the first cycle (3 weeks) of treatment.
Phase II: Once the optimal lapatinib dose has been chosen, all remaining patients will initiate treatment at this dose level. Patients with stable or responding disease after 6 cycles will continue treatment with lapatinib alone until progression of disease or intolerable side effects. Feasibility, toxicity and response rate of this combination will be assessed.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

Conditions: Adenocarcinoma of the Esophagus, Adenocarcinoma of the Gastroesophageal Junction
Being tested: Carboplatin AUC, Paclitaxel, lapatinib
Medical subject headings: Adenocarcinoma Of Esophagus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT01395537
Study group	Role	What they receive
Lapatinib With Carboplatin and Paclitaxel	Experimental	Not described Receives: Drug: Carboplatin AUC; Drug: Paclitaxel; Drug: lapatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: after 37 months

Secondary outcomes (1)

To Determine the Overall Survival
Overall survival is defined as the length of time between the date of starting treatment and death due to any cause. For a patient who is alive at the time of the statistical analysis, the patient will be considered censored at the last date of known contact.
Measured: after 37 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2011Dec 2014

First posted15 Jul 2011 (estimated)
Study startAug 2011
Primary completionDec 2014
Study completionDec 2014

Why it stopped: Research Cancelled

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Adenocarcinoma of the EsophagusStudies of the same condition, open and under way.
More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01395537
Sponsor's protocol ID: CASE2310
Status last verified: Mar 2019
First submitted: 12 Jul 2011
Last updated: 19 Mar 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Multicenter Prospective Cohort on Esophageal Endoscopic Submucosal Dissection
Superficial Esophageal Cancer, Oesophageal Adenocarcinoma
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
RecruitingPhase 1/2
Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread
Metastatic Breast Cancer, Metastatic Gastric Adenocarcinoma
Recruiting
Individually Tailored, Supervised, Remote Exercise Intervention to Improve Physical Function for Stage I-III Gastroesophageal Cancer Survivors, PRECISE Trial
Clinical Stage I Esophageal Adenocarcinoma American Joint Committee on Cancer (AJCC) v8, Clinical Stage I Esophageal Squamous Cell Carcinoma AJCC v8
RecruitingPhase 2/3
A Study to Evaluate the Safety and Efficacy of Pumitamig in Combination With Chemotherapy Versus Nivolumab in Combination With Chemotherapy in Participants With Previously Untreated Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (ROSETTA Gastric-204)
Untreated Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma

All Adenocarcinoma of the Esophagus trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I/II Pilot Study of Lapatinib in Combination With Carboplatin and Paclitaxel in the Treatment of Recurrent/Metastatic Adenocarcinoma of the Esophagus and Gastroesophageal Junction (GEJ)
ClinicalTrials.gov ID: NCT01395537
Acronym / sponsor ID: CASE2310
Conditions: Adenocarcinoma of the Esophagus, Adenocarcinoma of the Gastroesophageal Junction
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Research Cancelled
Enrolment: 13 participants (actual)
Lead sponsor: Case Comprehensive Cancer CenterUniversity, hospital or other
Study start: Aug 2011 (actual)
Primary completion: Dec 2014 (actual)
Study completion: Dec 2014 (actual)
First posted: 15 Jul 2011 (estimated)
Results: Posted 26 Feb 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

RATIONALE: Since lapatinib inhibits both EGFR and HER2 receptors, it is an attractive agent for the treatment of esophageal and GEJ tumors.

Detailed description

OBJECTIVES:

Phase I: To assess the toxicity and feasibility of the addition of lapatinib to carboplatin and paclitaxel in patients with recurrent/metastatic adenocarcinoma of the esophagus and gastroesophageal junction.
Phase II: To assess the response rate to this regimen.

OUTLINE:

There will be an initial phase I safety cohort studies requiring up to 12 patients, followed by a phase II cohort using the lapatinib dose defined in phase I. Carboplatin and paclitaxel doses will not be escalated. The initial dose of lapatinib of 750 mg daily by mouth will be given to 6 patients. There will be no dose escalation of the lapatinib above 1000 mg daily. The lapatinib dose for the phase II cohort of this trial will be based only on toxicities experienced during the first cycle (3 weeks) of treatment.
Phase II: Once the optimal lapatinib dose has been chosen, all remaining patients will initiate treatment at this dose level. Patients with stable or responding disease after 6 cycles will continue treatment with lapatinib alone until progression of disease or intolerable side effects. Feasibility, toxicity and response rate of this combination will be assessed.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Lapatinib With Carboplatin and Paclitaxel	Experimental	Drug: Carboplatin AUC, Drug: Paclitaxel, Drug: lapatinib

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

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.

Key exclusion criteria (14 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Carboplatin AUCCarboplatin 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.	Drug	Lapatinib With Carboplatin and Paclitaxel
PaclitaxelPaclitaxel 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.	Drug	Lapatinib With Carboplatin and Paclitaxel
lapatinibLapatinib should be taken once daily, at the same time daily, on an empty stomach, either 1 hour before, or 1 hour after meals.	Drug	Lapatinib With Carboplatin and Paclitaxel

Primary outcome

PHASE I: Number of Patients That Experience a Grade 3-4 Dose Limiting Toxicity
Time frame: after 9 weeks (3 cycles) of treatment
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.
PHASE II: To Assess the Response Rate to This Regimen.
Time frame: after 37 months
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.

1 secondary outcome

To Determine the Overall Survival
Time frame: after 37 months

Results and safety

Results posted to the registry on 26 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lapatinib With Carboplatin and Paclitaxel	13	13

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

Time frame: after 9 weeks (3 cycles) of treatment. Count of participants. Unit: Participants

Measure	Lapatinib With Carboplatin and Paclitaxel n = 13
Value	1

Population analysed: All participants that received treatment

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

Time frame: after 37 months. Count of participants. Unit: Participants

Measure	Lapatinib With Carboplatin and Paclitaxel n = 1
Value	0

Population analysed: Participants eligible to move to phase II of study. Study was cancelled prior to additional participants moving to study.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Adverse events were collected while participants were on study ranging from 4 to 19 months.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lapatinib With Carboplatin and Paclitaxel	4 of 13 (30.8%)	11 of 13 (84.6%)	13 of 13

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Adenocarcinoma of the Esophagus

RecruitingObservational study
Multicenter Prospective Cohort on Esophageal Endoscopic Submucosal Dissection
Superficial Esophageal Cancer, Oesophageal Adenocarcinoma
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
RecruitingPhase 1/2
Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread
Metastatic Breast Cancer, Metastatic Gastric Adenocarcinoma
Recruiting
Individually Tailored, Supervised, Remote Exercise Intervention to Improve Physical Function for Stage I-III Gastroesophageal Cancer Survivors, PRECISE Trial
Clinical Stage I Esophageal Adenocarcinoma American Joint Committee on Cancer (AJCC) v8, Clinical Stage I Esophageal Squamous Cell Carcinoma AJCC v8
RecruitingPhase 2/3
A Study to Evaluate the Safety and Efficacy of Pumitamig in Combination With Chemotherapy Versus Nivolumab in Combination With Chemotherapy in Participants With Previously Untreated Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (ROSETTA Gastric-204)
Untreated Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David Adelstein, MD principal investigator

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Neelesh Sharma, MD principal investigator

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

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PHASE I: Number of Patients That Experience a Grade 3-4 Dose Limiting Toxicity (time frame: after 9 weeks (3 cycles) of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01395537.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2019.