Trial Outcomes & Findings for Study of 5-FU, Oxaliplatin, & Lapatinib Combined With Radiation Therapy to Treat HER2 Positive Esophagogastric Cancer (NCT NCT01769508)
NCT ID: NCT01769508
Last Updated: 2016-06-13
Results Overview
Defined as the absence of invasive tumor in esophagogastric and lymph node tissue removed at time of surgery, as judged by the local pathologist. An improvement in pCR rate from 30 percent (historical) to 50 percent is the primary efficacy endpoint.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
12 participants
Primary outcome timeframe
18 months
Results posted on
2016-06-13
Participant Flow
Participant milestones
| Measure |
Combined Therapy
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
5-Fluorouracil: 5-FU, 225 mg/m2 IVCI, during XRT.
Oxaliplatin: Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.
Lapatinib: Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion
Radiation Therapy: Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
6
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
Combined Therapy
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
5-Fluorouracil: 5-FU, 225 mg/m2 IVCI, during XRT.
Oxaliplatin: Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.
Lapatinib: Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion
Radiation Therapy: Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6
|
|---|---|
|
Overall Study
Death
|
3
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
Baseline Characteristics
Study of 5-FU, Oxaliplatin, & Lapatinib Combined With Radiation Therapy to Treat HER2 Positive Esophagogastric Cancer
Baseline characteristics by cohort
| Measure |
Combined Therapy
n=12 Participants
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
5-Fluorouracil: 5-FU, 225 mg/m2 IVCI, during XRT.
Oxaliplatin: Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.
Lapatinib: Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion
Radiation Therapy: Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6
|
|---|---|
|
Age, Continuous
|
64 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 18 monthsPopulation: All patients who underwent surgery
Defined as the absence of invasive tumor in esophagogastric and lymph node tissue removed at time of surgery, as judged by the local pathologist. An improvement in pCR rate from 30 percent (historical) to 50 percent is the primary efficacy endpoint.
Outcome measures
| Measure |
Combined Therapy
n=3 Participants
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
5-Fluorouracil: 5-FU, 225 mg/m2 IVCI, during XRT.
Oxaliplatin: Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.
Lapatinib: Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion
Radiation Therapy: Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6
|
|---|---|
|
Pathologic Complete Response Rate (pCR Rate)
|
1 participants
|
PRIMARY outcome
Timeframe: 18 monthsAn additional primary objective is to evaluate the safety and optimal dose of lapatinib when added to 5-FU, oxaliplatin and radiation therapy.
Outcome measures
| Measure |
Combined Therapy
n=12 Participants
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
5-Fluorouracil: 5-FU, 225 mg/m2 IVCI, during XRT.
Oxaliplatin: Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.
Lapatinib: Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion
Radiation Therapy: Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6
|
|---|---|
|
Safety and Optimal Dose of Regimen
|
750 mg QD Lapatinib
|
SECONDARY outcome
Timeframe: 18 monthsThe Percentage of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Combined Therapy
n=12 Participants
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
5-Fluorouracil: 5-FU, 225 mg/m2 IVCI, during XRT.
Oxaliplatin: Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.
Lapatinib: Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion
Radiation Therapy: Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6
|
|---|---|
|
Progression Free Survival (PFS)
|
3.253 months
Interval 1.183 to 6.768
|
SECONDARY outcome
Timeframe: 18 monthsPopulation: All treated patients
Defined as the frequency of adverse events for patients who received at least one dose of study treatment, and assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.
Outcome measures
| Measure |
Combined Therapy
n=12 Participants
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
5-Fluorouracil: 5-FU, 225 mg/m2 IVCI, during XRT.
Oxaliplatin: Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.
Lapatinib: Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion
Radiation Therapy: Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6
|
|---|---|
|
Toxicity Profile for Treated Patients
Nausea
|
9 participants
|
|
Toxicity Profile for Treated Patients
Diarrhea
|
7 participants
|
|
Toxicity Profile for Treated Patients
Fatigue
|
6 participants
|
|
Toxicity Profile for Treated Patients
Vomiting
|
5 participants
|
|
Toxicity Profile for Treated Patients
Mucositis
|
4 participants
|
|
Toxicity Profile for Treated Patients
Stomatitis
|
3 participants
|
|
Toxicity Profile for Treated Patients
Anemia
|
2 participants
|
|
Toxicity Profile for Treated Patients
Anorexia
|
2 participants
|
|
Toxicity Profile for Treated Patients
Constipation
|
2 participants
|
|
Toxicity Profile for Treated Patients
Dehydration
|
2 participants
|
|
Toxicity Profile for Treated Patients
Dysesthesia
|
2 participants
|
|
Toxicity Profile for Treated Patients
Dysgeusia
|
2 participants
|
|
Toxicity Profile for Treated Patients
Dysphagia
|
2 participants
|
|
Toxicity Profile for Treated Patients
Esophagitis
|
2 participants
|
|
Toxicity Profile for Treated Patients
Cold sensitivity
|
2 participants
|
|
Toxicity Profile for Treated Patients
Hypokalemia
|
2 participants
|
|
Toxicity Profile for Treated Patients
Peripheral sensory neuropathy
|
2 participants
|
|
Toxicity Profile for Treated Patients
Thrombocytopenia
|
2 participants
|
|
Toxicity Profile for Treated Patients
Rash
|
2 participants
|
|
Toxicity Profile for Treated Patients
Thromboembolic event
|
2 participants
|
SECONDARY outcome
Timeframe: 18 monthsTime to progression is defined as the time between day 1 cycle 1 and time to first documented disease progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Outcome measures
| Measure |
Combined Therapy
n=12 Participants
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
5-Fluorouracil: 5-FU, 225 mg/m2 IVCI, during XRT.
Oxaliplatin: Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.
Lapatinib: Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion
Radiation Therapy: Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6
|
|---|---|
|
Time to Progression (TTP)
|
6.768 months
Interval 6.604 to 6.965
|
SECONDARY outcome
Timeframe: 18 monthsThe Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Outcome measures
| Measure |
Combined Therapy
n=12 Participants
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
5-Fluorouracil: 5-FU, 225 mg/m2 IVCI, during XRT.
Oxaliplatin: Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.
Lapatinib: Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion
Radiation Therapy: Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6
|
|---|---|
|
Overall Survival (OS)
|
NA months
Median OS has not been reached as not enough death events have occurred at this time point
|
Adverse Events
Combined Therapy
Serious events: 6 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Combined Therapy
n=12 participants at risk
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
5-Fluorouracil: 5-FU, 225 mg/m2 IVCI, during XRT.
Oxaliplatin: Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.
Lapatinib: Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion
Radiation Therapy: Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6
|
|---|---|
|
Immune system disorders
Allergic Reaction
|
8.3%
1/12 • 26 months
|
|
Cardiac disorders
Cardiac arrest
|
8.3%
1/12 • 26 months
|
|
General disorders
Death NOS
|
8.3%
1/12 • 26 months
|
|
Metabolism and nutrition disorders
Dehydration
|
8.3%
1/12 • 26 months
|
|
Gastrointestinal disorders
Diarrhea
|
8.3%
1/12 • 26 months
|
|
Eye disorders
Eye disorders - Other, vision changes
|
8.3%
1/12 • 26 months
|
|
General disorders
General disorders and administration site conditions - Other, hemorrhage
|
8.3%
1/12 • 26 months
|
|
Cardiac disorders
Heart Failure
|
8.3%
1/12 • 26 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
8.3%
1/12 • 26 months
|
|
Infections and infestations
Infections and infestations - Other, pneumonia
|
8.3%
1/12 • 26 months
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, malnutrition
|
8.3%
1/12 • 26 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, benign pituitary tumor
|
8.3%
1/12 • 26 months
|
|
Infections and infestations
Sepsis
|
8.3%
1/12 • 26 months
|
Other adverse events
| Measure |
Combined Therapy
n=12 participants at risk
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
5-Fluorouracil: 5-FU, 225 mg/m2 IVCI, during XRT.
Oxaliplatin: Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.
Lapatinib: Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion
Radiation Therapy: Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6
|
|---|---|
|
Gastrointestinal disorders
Nausea
|
75.0%
9/12 • 26 months
|
|
Gastrointestinal disorders
Diarrhea
|
58.3%
7/12 • 26 months
|
|
General disorders
Fatigue
|
50.0%
6/12 • 26 months
|
|
Gastrointestinal disorders
Vomiting
|
41.7%
5/12 • 26 months
|
|
Gastrointestinal disorders
Mucositis
|
33.3%
4/12 • 26 months
|
|
Investigations
Weight Loss
|
33.3%
4/12 • 26 months
|
|
Metabolism and nutrition disorders
Dehydration
|
25.0%
3/12 • 26 months
|
|
Gastrointestinal disorders
Dysphagia
|
25.0%
3/12 • 26 months
|
|
Gastrointestinal disorders
Gastrointestinal Disorders - Other, Stomatitis
|
25.0%
3/12 • 26 months
|
|
Blood and lymphatic system disorders
Anemia
|
16.7%
2/12 • 26 months
|
|
Metabolism and nutrition disorders
Anorexia
|
16.7%
2/12 • 26 months
|
|
Gastrointestinal disorders
Constipation
|
16.7%
2/12 • 26 months
|
|
Nervous system disorders
Dysesthesia
|
16.7%
2/12 • 26 months
|
|
Nervous system disorders
Dysgeusia
|
16.7%
2/12 • 26 months
|
|
Gastrointestinal disorders
Esophagitis
|
16.7%
2/12 • 26 months
|
|
General disorders
General Disorders And Administration Site Conditions - Other, Cold Sensitivity
|
16.7%
2/12 • 26 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
16.7%
2/12 • 26 months
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
16.7%
2/12 • 26 months
|
|
Investigations
Platelet Count Decreased
|
16.7%
2/12 • 26 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
2/12 • 26 months
|
|
Vascular disorders
Thromboembolic Event
|
16.7%
2/12 • 26 months
|
|
Gastrointestinal disorders
Abdominal Pain
|
8.3%
1/12 • 26 months
|
|
Immune system disorders
Allergic Reaction
|
8.3%
1/12 • 26 months
|
|
Cardiac disorders
Cardiac Arrest
|
8.3%
1/12 • 26 months
|
|
General disorders
Death Nos
|
8.3%
1/12 • 26 months
|
|
General disorders
Edema Limbs
|
8.3%
1/12 • 26 months
|
|
Eye disorders
Eye Disorders - Other, Vision Changes
|
8.3%
1/12 • 26 months
|
|
Injury, poisoning and procedural complications
Fall
|
8.3%
1/12 • 26 months
|
|
General disorders
General Disorders And Administration Site Conditions - Other, Hemorrhage
|
8.3%
1/12 • 26 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
8.3%
1/12 • 26 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
8.3%
1/12 • 26 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
8.3%
1/12 • 26 months
|
|
Infections and infestations
Infections And Infestations - Other, Pneumonia
|
8.3%
1/12 • 26 months
|
|
Psychiatric disorders
Insomnia
|
8.3%
1/12 • 26 months
|
|
Metabolism and nutrition disorders
Metabolism And Nutrition Disorders - Other, Malnutrition
|
8.3%
1/12 • 26 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.3%
1/12 • 26 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms Benign, Malignant And Unspecified (Incl Cysts And Polyps) - Other, Pituitary Macroadenoma
|
8.3%
1/12 • 26 months
|
|
Nervous system disorders
Paresthesia
|
8.3%
1/12 • 26 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.3%
1/12 • 26 months
|
|
Skin and subcutaneous tissue disorders
Rash Maculo-Papular
|
8.3%
1/12 • 26 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
8.3%
1/12 • 26 months
|
|
Infections and infestations
Sepsis
|
8.3%
1/12 • 26 months
|
|
Cardiac disorders
Sinus Tachycardia
|
8.3%
1/12 • 26 months
|
|
Infections and infestations
Skin Infection
|
8.3%
1/12 • 26 months
|
|
Investigations
White Blood Cell Decreased
|
8.3%
1/12 • 26 months
|
Additional Information
John D Hainsworth, MD
Sarah Cannon Research Institute
Phone: 1-877-691-7274
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 but =180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites
- Publication restrictions are in place
Restriction type: OTHER