Adenocarcinoma
Conditions
Keywords
Gastric, Esophagogastric
Brief summary
The purpose of this study is to determine if doctors can use the results of special tests of subjects tumor tissue, that will look for specific abnormalities in the tumor, to choose a specific drug that is targeted to work against that abnormality (called molecular profiling) and to see what effects (good and/or bad) that targeted drug has on subjects cancer when it is given with standard chemotherapy.
Interventions
DRUGTrastuzumab
Trastuzumab
DRUGABT-806
ABT-806
DRUGBemarituzumab
Bemarituzumab
DRUGRamucirumab
Ramucirumab
DRUGNivolumab
Nivolumab
DRUGStandard cytotherapy
FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)
Sponsors
AbbVie
University of Chicago
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed metastatic gastric or esophagogastric junction (type I,II,III Siewert) adenocarcinoma 2. Newly-diagnosed chemo-naïve or recurrent after curative-intent surgery * \>6 months after completion of adjuvant therapy (including chemotherapy and/or radiotherapy) * No prior treatment with any targeted agent * Patients who have started first line mFOLFOX6 therapy (+/-trastuzumab for HER2 amplified tumors) may be considered for trial participation if they have received no more than 4 doses of therapy at the time of consent and screening. 3. Measurable metastatic disease by RECIST criteria, * Must be amenable to ultrasound or CT-guided biopsy of one metastatic lesion * Peritoneal disease as the sole site of occult metastasis or presenting as malignant ascites is acceptable if a cell block of tumor cells can be obtained showing \>20% viable tumor cells. 4. ECOG PS 0,1 5. Age \> 18 years 6. Patients must have normal organ and marrow function as defined below: * granulocytes \>1,2500/mcL * platelets \>100,000/mcL * total bilirubin \< 1.5 x ULN, \<1.8 x ULN with liver metastases * AST(SGOT)/ALT(SGPT) \<2.5 X ULN without liver metastases; \<5 X ULN with liver metastases * creatinine within normal institutional limits (\<1.5) OR * creatinine clearance \>50 mL/min/1.73m2, (for creatinine level above normal) * INR: \< 1.5 (patients on warfarin need to be converted to LMWH during study participation to be eligible) 7. Consent to baseline metastatic and progressive disease biopsy (of metastatic/progressing lesion) for enabling biomarker assessment and treatment assignment (at each time point - baseline, PD1, PD2, PD3) as well as for correlative studies. • Consent to baseline and serial blood draws for plasma/serum/whole blood banking for correlative studies 8. Ability to understand and the willingness to sign a written informed consent document and consent to the serial nature of the proposed PANGEA treatment with first, second and third line therapy as tolerated. 9. Ability to comply with requirements of the protocol, as assessed by the investigator by the patient signing the consent form. 10. If history of exposure to anthracyclines during perioperative treatment, the following cumulative doses of anthracyclines must be less than: Epirubicin \< 720 mg/m2 Doxorubicin or liposomal doxorubicin \< 360 mg/m2 Mitoxantrone \> 120 mg/m2 and idarubicin \> 90 mg/m2 If more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin. 11. Cardiac Ejection Fraction \>50% (for HER2+ patients) as assessed by echocardiogram, MUGA scan, or cardiac MRI 12. Willingness to use effective and reliable methods of contraception (For appropriate methods of contraception considered acceptable see Appendix B). Both men and women and members of all races and ethnic groups are eligible for this trial.
Exclusion criteria
1. No CVA within 6 months, no recent MI within 6 months 2. No currently active second malignancy 3. No uncontrolled intercurrent illness or infection 4. No peripheral edema \> grade 2 at baseline. 5. No peripheral neuropathy \> grade 2 at baseline. 6. No diarrhea \> grade 2 at baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 60 months | Time from enrollment to death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Biopsies Leading to an Adverse Event | 1 Month | Number of biopsies leading to an adverse event of the total undergoing baseline biopsies of a primary and metastatic disease site (liver, lung, lymph node, peritoneum/carcinomatosis). |
| Completion of Biopsy and Successful, Molecularly-based Treatment Assignment | Up to 1 month | Completion of biopsies with successful assignment per the treatment algorithm. Biomarker profile assays included next generation sequencing (NGS). EGFR expression was performed by selected-reaction-monitoring mass spectrometry (SRM-MS). |
| Adverse Event From Serial Biopsy for Second-line Treatment | Up to 60 Months | Number of participants with adverse events from serial biopsies of progressing metastatic disease sites (liver, lung, lymph node, peritoneum/carcinomatosis) |
| Adverse Event From Serial Biopsy for Third-line Treatment | Up to 60 months | Number of participants with adverse events from serial biopsies of progressing metastatic disease sites (liver, lung, lymph node, peritoneum/carcinomatosis) |
| Completion of Serial Biopsy for Third Line Therapy and Successful, Molecularly-based Treatment Assignment | Up to 60 months | Completion of biopsy with successful treatment assignment per the treatment algorithm. Biomarker profile assays included next generation sequencing (NGS). EGFR expression was performed by selected-reaction-monitoring mass spectrometry (SRM-MS). |
| Completion of Serial Biopsy for Second Line Therapy and Successful, Molecularly-based Treatment Assignment | Up to 60 months | Completion of biopsy with successful treatment assignment per the treatment algorithm. Biomarker profile assays included next generation sequencing (NGS). EGFR expression was performed by selected-reaction-monitoring mass spectrometry (SRM-MS). |
Other
| Measure | Time frame | Description |
|---|---|---|
| First-line Progression-free Survival | Up to 60 Months | Time from enrollment to progression or death during first-line treatment. 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. |
| Objective Response to First Line Therapy | Up to 6 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ITT-PTS: Personalized Treatment Strategy For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows:
Immuno-oncology patients including PD-L1 IHC combined positivity score \>10, high microsatellite instability, tumor mutation burden \>15 mutations/megabase, and/or Epstein-Barr virus positive patients received standard cytoptherapy plus Nivolumab
HER2 amplified patients received standard cytotherapy plus Trastuzumab
EGFR amplified patients received standard cytotherapy plus ABT-806
FGFR2 amplified patients received standard cytotherapy plus Bemarituzumab
MAPK/PIK3CA aberrant patients received standard cytotherapy plus Ramucirumab.
EGFR expressing patients received standard cytotherapy plus ABT 806.
All negative patients received standard cytotherapy plus Ramucirumab. | 68 |
| Non-ITT: Standard Therapy For patients without monoclonal antibodies available, therapy was standard cytotherapy consisting of FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line) | 12 |
| Total | 80 |
Baseline characteristics
| Characteristic | Non-ITT: Standard Therapy | Total | ITT-PTS: Personalized Treatment Strategy |
|---|---|---|---|
| Age, Continuous | 61 years | 61 years | 61 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 7 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 68 Participants | 57 Participants |
| Region of Enrollment United States | 12 participants | 80 participants | 68 participants |
| Sex: Female, Male Female | 1 Participants | 16 Participants | 15 Participants |
| Sex: Female, Male Male | 11 Participants | 64 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 56 / 68 | 11 / 12 |
| other Total, other adverse events | 68 / 68 | 12 / 12 |
| serious Total, serious adverse events | 29 / 68 | 8 / 12 |
Outcome results
Primary
Overall Survival
Time from enrollment to death from any cause.
Time frame: Up to 60 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ITT-PTS: Personalized Treatment Strategy | Overall Survival | 15.7 months |
| Non-ITT: Standard Therapy | Overall Survival | 9.0 months |
p-value: 0.0024One-sided Z-test
Secondary
Adverse Event From Serial Biopsy for Second-line Treatment
Number of participants with adverse events from serial biopsies of progressing metastatic disease sites (liver, lung, lymph node, peritoneum/carcinomatosis)
Time frame: Up to 60 Months
Population: This includes subset of patients administered second-line treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ITT-PTS: Personalized Treatment Strategy | Adverse Event From Serial Biopsy for Second-line Treatment | 0 Participants |
| Non-ITT: Standard Therapy | Adverse Event From Serial Biopsy for Second-line Treatment | 0 Participants |
Secondary
Adverse Event From Serial Biopsy for Third-line Treatment
Number of participants with adverse events from serial biopsies of progressing metastatic disease sites (liver, lung, lymph node, peritoneum/carcinomatosis)
Time frame: Up to 60 months
Population: This includes subset of patients administered third-line treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ITT-PTS: Personalized Treatment Strategy | Adverse Event From Serial Biopsy for Third-line Treatment | 0 Participants |
| Non-ITT: Standard Therapy | Adverse Event From Serial Biopsy for Third-line Treatment | 0 Participants |
Secondary
Completion of Biopsy and Successful, Molecularly-based Treatment Assignment
Completion of biopsies with successful assignment per the treatment algorithm. Biomarker profile assays included next generation sequencing (NGS). EGFR expression was performed by selected-reaction-monitoring mass spectrometry (SRM-MS).
Time frame: Up to 1 month
Population: Unit of analysis is the biopsy. Two biopsies were performed per patient, one of the primary tumor and one from a metastatic site.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ITT-PTS: Personalized Treatment Strategy | Completion of Biopsy and Successful, Molecularly-based Treatment Assignment | 134 biopsies |
| Non-ITT: Standard Therapy | Completion of Biopsy and Successful, Molecularly-based Treatment Assignment | 23 biopsies |
Secondary
Completion of Serial Biopsy for Second Line Therapy and Successful, Molecularly-based Treatment Assignment
Completion of biopsy with successful treatment assignment per the treatment algorithm. Biomarker profile assays included next generation sequencing (NGS). EGFR expression was performed by selected-reaction-monitoring mass spectrometry (SRM-MS).
Time frame: Up to 60 months
Population: This includes subset of patients administered second-line treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ITT-PTS: Personalized Treatment Strategy | Completion of Serial Biopsy for Second Line Therapy and Successful, Molecularly-based Treatment Assignment | 51 Participants |
| Non-ITT: Standard Therapy | Completion of Serial Biopsy for Second Line Therapy and Successful, Molecularly-based Treatment Assignment | 9 Participants |
Secondary
Completion of Serial Biopsy for Third Line Therapy and Successful, Molecularly-based Treatment Assignment
Completion of biopsy with successful treatment assignment per the treatment algorithm. Biomarker profile assays included next generation sequencing (NGS). EGFR expression was performed by selected-reaction-monitoring mass spectrometry (SRM-MS).
Time frame: Up to 60 months
Population: This includes subset of patients administered third-line treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ITT-PTS: Personalized Treatment Strategy | Completion of Serial Biopsy for Third Line Therapy and Successful, Molecularly-based Treatment Assignment | 21 Participants |
| Non-ITT: Standard Therapy | Completion of Serial Biopsy for Third Line Therapy and Successful, Molecularly-based Treatment Assignment | 3 Participants |
Secondary
Number of Biopsies Leading to an Adverse Event
Number of biopsies leading to an adverse event of the total undergoing baseline biopsies of a primary and metastatic disease site (liver, lung, lymph node, peritoneum/carcinomatosis).
Time frame: 1 Month
Population: Unit of analysis is the biopsy. Each patient had two biopsies, one of the primary tumor and one of a metastatic site.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ITT-PTS: Personalized Treatment Strategy | Number of Biopsies Leading to an Adverse Event | 1 biopsies |
| Non-ITT: Standard Therapy | Number of Biopsies Leading to an Adverse Event | 0 biopsies |
Other Pre-specified
First-line Progression-free Survival
Time from enrollment to progression or death during first-line treatment. 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.
Time frame: Up to 60 Months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ITT-PTS: Personalized Treatment Strategy | First-line Progression-free Survival | 8.2 months |
| Non-ITT: Standard Therapy | First-line Progression-free Survival | 6.7 months |
Other Pre-specified
Objective Response to First Line Therapy
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: 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.
Time frame: Up to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ITT-PTS: Personalized Treatment Strategy | Objective Response to First Line Therapy | 40 Participants |
| Non-ITT: Standard Therapy | Objective Response to First Line Therapy | 4 Participants |