Planning Treatment for Oesophago-gastric Cancer: a Maintenance Therapy Trial
- Conditions
- Adenocarcinoma of the StomachAdenocarcinoma of the OesophagusAdenocarcinoma of the Gastro-oesophageal Junction
- Interventions
- Registration Number
- NCT02678182
- Lead Sponsor
- Royal Marsden NHS Foundation Trust
- Brief Summary
To evaluate the efficacy of maintenance therapies following completion of standard first-line chemotherapy in patients with locally advanced or metastatic HER-2 positive or HER-2 negative oesophago-gastric adenocarcinomas.
- Detailed Description
This is a prospective, open label, multicentre, randomised phase II clinical trial. An adaptive trial design is proposed to allow ineffective treatments to be discontinued early, and to potentially add novel treatment arms as the trial progresses.
Patients will initially receive standard chemotherapy for their locally advanced or metastatic oesophago-gastric adenocarcinoma, according to local practice based upon their HER-2 status (tested locally). In order to be eligible for trial entry, HER-2 negative patients should have received a platinum-fluoropyrimidine based chemotherapy doublet of either cisplatin + capecitaine (CX), oxaliplatin + capecitabine (CAPOX), or 5FU + oxaliplatin (FOLFOX) (Arm A), whilst HER-2 positive patients (IHC 3+ or IHC 2+ and FISH positive) should have received cisplatin in combination with either capecitabine or 5-FU (CX or CF) plus trastuzumab chemotherapy (Arm B). Potentially eligible patients will be registered with the trials office whilst undergoing first line chemotherapy.
Patients will become eligible for trial recruitment and randomisation after 18 weeks standard chemotherapy with stable disease (SD) or better on the end-of-treatment CT scan. Please note: if your patient has been receiving a regimen delivered every three weeks (e.g. CX) they should have completed 6 cycles. If your patient has been receiving a regimen delivered every 2 weeks (e.g. FOLFOX) they should have received 9 cycles of treatment. Eligible patients will then be randomised according to HER-2 status as follows:
* HER-2 positive patients (\~20%) will be assigned maintenance single-agent trastuzumab (current UK standard)
* HER-2 negative patients (\~80%) will be randomised 1:1 between surveillance (current UK standard) and maintenance capecitabine.
Patients will be stratified according to: centre region, disease extent and performance status (0 versus 1 versus 2).
Review of patients will occur every 4 weeks in the surveillance arm. In maintenance therapy arms, patients will be reviewed every 3 or every 4 weeks depending upon the treatment strategy. CT assessments of response will occur every 12 weeks (3 months) in all arms of the trial. Treatment will be continued until disease progression, unacceptable toxicity, or patient withdrawal for another reason.
The trial is being run from the RM GI and Lymphoma CTU with Professor David Cunningham as the Chief Investigator (CI). Effective arms in the phase II portion of the trial may be taken forward into a phase III maintenance trial powered for overall survival. It is also hoped that, as more robust data becomes available for other biomarker-selected populations (e.g. MET-positive, FGFR-amplified), it may be possible to amend the overall trial design to incorporate these biomarker-targeted maintenance therapies in the HER-2 negative population.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 924
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B1: Trastuzumab Maintenance Trastuzumab 6mg/kg on day 1 every 21 days Arm A4: Rucaparib Rucaparib 600mg PO twice daily Arm A2: Capecitabine Maintenance Capecitabine 1250 mg/M2/DAY on days 1-21 Arm A3: MEDI4736 (Durvalumab) MEDI4736 (Durvalumab) IV treatment on day 1 +15, on a 28 day cycle. Arm A5: Capecitabine and Ramucirumab Capecitabine capecitabine 1250 mg/m2/day PO in two divided doses continuously from days 1-21 of each 21 day cycle (see section 12) and ramucirumab 8mg/kg IV day 1 and day 8 Arm A5: Capecitabine and Ramucirumab Ramucirumab capecitabine 1250 mg/m2/day PO in two divided doses continuously from days 1-21 of each 21 day cycle (see section 12) and ramucirumab 8mg/kg IV day 1 and day 8
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) 5 years The progression free survival will be calculated from the date of randomisation to the date of disease progression according to RECIST 1.1 criteria or death from any cause, whichever comes first. In HER 2 negative patients the PFS will be compared between the standard Arm (A1) and capecitabine (A2) and then separately between standard arm (A1) and MEDI 4736 (A3), or standard arm (A1) and Rucaparib (A4), or standard arm (A1) and Ramucirumab (A5).
- Secondary Outcome Measures
Name Time Method Analysis of PFR may also be conducted according to biomarker status in relevant arms. For example in HER2 negative patients outcomes in Arm A1 and A3 will be compared according to PDL1 expression status assessed by immunohistochemistry on tissue. 5 years Analysis of PFR may also be conducted according to biomarker status in relevant arms. For example in HER2 negative patients outcomes in Arm A1 and A3 will be compared according to PDL1 expression status assessed by immunohistochemistry on tissue.
Analysis of OS may also be conducted according to biomarker status in relevant arms. For example in HER2 negative patients outcomes in Arm A1 and A3 will be compared according to PDL1 expression status assessed by immunohistochemistry on tissue. 5 years Analysis of OS may also be conducted according to biomarker status in relevant arms. For example in HER2 negative patients outcomes in Arm A1 and A3 will be compared according to PDL1 expression status assessed by immunohistochemistry on tissue.
Overall survival (OS) 5 years Will be calculated from the date of randomisation until the date of death from any cause. Patients remaining alive at the time of the analysis will be censored a the date of last follow up.
Progression - free rate (PFR) 5 years Progression-free rate (defined as stable disease, partial or complete response) at 12 weeks (3 months) , 24 weeks (6 months) and 52 weeks (1 year) will be evaluated using RECIST 1.1 criteria. Progression events will be determined by local investigator assessment, and will be collected for up to a 5 year period.
Objective response rate (ORR) by RECIST 1.1 5 years This will be evaluated according to RECIST 1.1.
The number of participants with treatment related adverse events as assessed by CTCAE v 4.0 5 years The number of participants with treatment related adverse events as assessed by CTCAE v 4.0
Analysis of PFS may also be conducted according to biomarker status in relevant arms. For example in HER2 negative patients outcomes in Arm A1 and A3 may be compared according to PDL1 expression status assessed by immunohistochemistry on tissue. 5 years Analysis of PFS may also be conducted according to biomarker status in relevant arms. For example in HER2 negative patients outcomes in Arm A1 and A3 may be compared according to PDL1 expression status assessed by immunohistochemistry on tissue.
Analysis of ORR may also be conducted according to biomarker status in relevant arms. For example in HER2 negative patients outcomes in Arm A1 and A3 will be compared according to PDL1 expression status assessed by immunohistochemistry on tissue. 5 years Analysis of ORR may also be conducted according to biomarker status in relevant arms. For example in HER2 negative patients outcomes in Arm A1 and A3 will be compared according to PDL1 expression status assessed by immunohistochemistry on tissue.
Trial Locations
- Locations (1)
The Royal Marsden NHS Foundation Trust, Downs Road, Sutton
🇬🇧Sutton, United Kingdom