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

NCT02678182 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 3804
• Study Type: interventional
• Target: 494
• Locations: 1 country
• Sites: 1

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.

Conditions

Adenocarcinoma of the Oesophagus; Adenocarcinoma of the Gastro-oesophageal Junction; Adenocarcinoma of the Stomach

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  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).

  5 years

Secondary Outcomes (8)

• Progression - free rate (PFR)

  5 years

• Overall survival (OS)

  5 years

• Objective response rate (ORR) by RECIST 1.1

  5 years

• The number of participants with treatment related adverse events as assessed by CTCAE v 4.0

  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.

  5 years

Study Arms (6)

A1: Surveillance

NO INTERVENTION

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

Arm A2: Capecitabine Maintenance

EXPERIMENTAL

1250 mg/M2/DAY on days 1-21

Drug: Capecitabine

Arm A3: MEDI4736 (Durvalumab)

EXPERIMENTAL

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

Drug: MEDI4736 (Durvalumab)

Arm B1: Trastuzumab Maintenance

ACTIVE COMPARATOR

6mg/kg on day 1 every 21 days

Drug: Trastuzumab

Arm A4: Rucaparib

EXPERIMENTAL

600mg PO twice daily

Drug: Rucaparib

Arm A5: Capecitabine and Ramucirumab

EXPERIMENTAL

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

Drug: Capecitabine; Drug: Ramucirumab

Interventions

Capecitabine DRUG

1250 mg/m2/day, 21 day cycle

Arm A2: Capecitabine Maintenance; Arm A5: Capecitabine and Ramucirumab

MEDI4736 (Durvalumab) DRUG

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

Arm A3: MEDI4736 (Durvalumab)

Trastuzumab DRUG

6mg/kg on day 1 cycle every 21 days

Arm B1: Trastuzumab Maintenance

Rucaparib DRUG

600mg PO twice daily

Arm A4: Rucaparib

Ramucirumab DRUG

ramucirumab 8mg/kg IV day 1 and day 8

Arm A5: Capecitabine and Ramucirumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically verified inoperable locally advanced or metastatic adenocarcinoma of the oesophagus, oesophago-gastric junction, or stomach.
• Completion of 18 weeks of first-line chemotherapy with either CX/ CAPOX or FOLFOX (HER2 negative) or CX/ CF + trastuzumab (HER2 positive) for locally advanced / metastatic disease with \> stable disease on the end of treatment CT scan (HER2 positive patients must have received at least one cycle of trastuzumab alongside first line chemotherapy; patients receiving chemotherapy delivered on a 3-weekly basis eg CX/ CAPOX should have received 6 cycles and on a two weekly basis e.g. FOLFOX should have received 9 cycles).
• Disease which, following first-line chemotherapy, remains inoperable and unsuitable for definitive chemoradiotherapy.
• Able to proceed with maintenance treatment within 28 days of the last day of the last cycle of chemotherapy.
• Formalin fixed paraffin embedded (FFPE) blocks of diagnostic tissue available for biomarker analysis.
• Any prior chemotherapy or radiotherapy in the adjuvant setting must have been completed at least 6 months prior to the first occurrence of metastatic disease.
• No prior radiotherapy in the advanced disease setting. Patients receiving palliative radiotherapy to sites of disease that are not measurable may be eligible and should be discussed with the Chief Investigator.
• Male/female patients aged ≥18 years.
• WHO Performance status 0, 1 or 2.
• Patients should have a projected life expectancy of at least 3 months.
• Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.5x109/l; white blood cell count ≥ 3x109/l; platelets ≥ 100x109/l; haemoglobin (Hb) ≥ 9g/dl (can be post-transfusion).
• Adequate renal function: calculated creatinine clearance ≥50ml/minute.
• Adequate liver function: serum bilirubin ≤1.5x ULN; aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤2.5 x ULN (5 × ULN is acceptable for ALT, AST and ALP if liver metastases are present).
• Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use an effective form of contraception during the study and for 7 months following the last dose of assigned study drug(s).
• Written informed consent must be obtained from the patient before any study-specific procedures are performed.

You may not qualify if:

• Concurrent enrolment in another clinical trial unless it is an observational (non-interventional) clinical study.
• Tumours of squamous histology.
• Documented brain metastases, central nervous system metastases or leptomeningeal disease.
• Patients who have not recovered from clinically significant effects of any prior surgery, radiotherapy or any other anti-neoplastic therapies. All toxicities must have resolved to grade 1 or less, with the exception of peripheral neuropathy which must be less than or equal to grade 2 according to NCI CTCAE version 4.0.
• Any major surgery within 4 weeks prior to the start of study treatment.
• Uncontrolled hypertension (systolic blood pressure \>180 mm Hg or diastolic blood pressure \>100 mm Hg).
• Clinically significant (i.e. active) cardiac disease e.g. symptomatic coronary artery disease, symptomatic congestive heart failure, uncontrolled cardiac dysrhythmia, or myocardial infarction within the last 12 months. Patients with any prior history of clinically significant cardiac failure are excluded from study entry.
• History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan.
• Lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, or inability to take oral medication.
• Patients who are pregnant or lactating.
• Known positive tests for human immunodeficiency virus (HIV) infection, hepatitis A or C virus, acute or chronic active hepatitis B infection.
• Other clinically significant disease or co-morbidity which may adversely affect the safe delivery of treatment within this trial.
• Any other malignancies within the last 3 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix).
• Treatment with another investigational agent within 30 days of commencing study treatment.
• Patients must have histologically or cytologically confirmed HER-2 negative disease (HER-2 0-2 by IHC; note if ISH testing is performed this must not demonstrate evidence of gene amplification).

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• MedImmune LLC: collaborator
• Clovis Oncology, Inc.: collaborator
• Eli Lilly and Company: collaborator
• AstraZeneca: collaborator

Study Sites (1)

The Royal Marsden NHS Foundation Trust, Downs Road, Sutton

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore). 2022 May 27;101(21):e29304. doi: 10.1097/MD.0000000000029304.

  PMID: 35623069 DERIVED

MeSH Terms

Interventions

Capecitabine; durvalumab; Trastuzumab; rucaparib; Ramucirumab

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2015
• First Posted: February 9, 2016
• Study Start: February 1, 2015
• Primary Completion: April 17, 2025
• Study Completion (Estimated): June 1, 2027
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)