Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Stomach Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Trastuzumab

Durvalumab

Ramucirumab

Rucaparib

Antimetabolites

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patients in this Arm will follow current UK standard of care for this setting and will be reviewed every 4 weeks

IV treatment on day 1 +15, on a 28 day cycle.

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

IV treatment on days 1\&15 of 28 day cycle

MEDI4736

Sue Cromarty

Dr Anderley Gordon

Shannon Kidd

Professor David Cunningham

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.

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.

Planning Treatment for Oesophago-gastric Cancer: a Maintenance Therapy Trial

Planning Treatment for Oesophago-gastric Cancer: a Randomised Maintenance Therapy Trial

Following trial completion the trial will be submitted for publication to a peer reviewed journal

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).

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.

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.

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

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 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.

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.

Spots Global Cancer Trial Database for adenocarcinoma of the oesophagus