Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03288350
Other study ID # MS100070_0073
Secondary ID
Status Recruiting
Phase Phase 2
First received September 15, 2017
Last updated March 20, 2018
Start date February 22, 2018
Est. completion date December 2023

Study information

Verified date March 2018
Source McGill University Health Center
Contact Touhid Opu, MBBS, MSc
Phone 514-934-1934
Email touhid.opu@mail.mcgill.ca
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a single-center, single-arm, open-label, Simon 2-stage, phase II trial in up to 55 patients with a potentially resectable, histologically-proven, adenocarcinoma or poorly differentiated carcinoma of the stomach, esophagogastric junction (EGJ), or lower third of the esophagus.

Patients will receive neoadjuvant therapy consisting of 4 cycles of avelumab added to the modified chemotherapy regimen of docetaxel, cisplatin, 5- fluorouracil. Following surgery, pathologic response will be assessed. Patients will then receive adjuvant therapy consisting of 4 cycles of mDCF + avelumab. Patients will be followed to assess two-year disease-free survival rates.

The primary objective of this study is to assess the effect on pathologic complete response rate (pCR) of adding avelumab to an mDCF regimen. The secondary objectives of this study are to determine the safety of adding avelumab to an mDCF regimen and assess its effect on two-year disease-free survival.


Recruitment information / eligibility

Status Recruiting
Enrollment 55
Est. completion date December 2023
Est. primary completion date December 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

1. Signed, informed consent;

2. Age 18 years or older;

3. Histological diagnosis of adenocarcinoma or poorly differentiated carcinoma of the stomach, esophagogastric junction (EGJ), or lower third of the esophagus;

4. The tumour must be deemed by the team to be potentially resectable. This includes imaging studies (detailed below) to clinically stage the tumor and rule out the presence of metastatic disease, and includes a preoperative laparoscopic evaluation for gastric tumors only;

5. Stage IB (TlNl only), II, IHA, IIIB;

6. Life expectancy greater than 3 months;

7. ECOG performance status of 0-1;

8. Neutrophils ~ 1500/µL;

9. Platelet count~ 100,000/µL;

10. Hemoglobin~ 9 g/dL;

11. Total bilirubin level :S 1.5 x the upper limit of normal (ULN) range unless consistent with Gilbert's syndrome (normal direct bilirubin);

12. AST and ALT :S 2.5 x ULN;

13. If serum creatinine above upper limit of normal (ULN), creatinine clearance ~ 60 ml/min as determined by 24-h creatinine clearance or Cockcroft-Gault formula;

14. Negative pregnancy test for women of child-bearing potential; and

15. Highly effective contraception for both male and female subjects throughout the study and for at least 60 days after last avelumab treatment administration if the risk of conception exists.

Exclusion Criteria:

1. Current or prior use of immunosuppressive medication, including corticosteroids, within 7 days prior to registration EXCEPT for the following:

1. intranasal, intra-ocular, inhaled, topical steroids, or local steroid injection (e.g., intraarticular injection);

2. Systemic corticosteroids at physiologic doses :S 10 mg/day of prednisone or equivalent;

3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication);

2. Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. However, patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible;

3. Prior organ transplantation, including allogeneic stem cell transplantation;

4. Squamous-cell carcinoma diagnosis;

5. Significant acute or chronic active infections requiring systemic therapy, including, among others:

1. Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);

2. Positive test for HBV surface antigen and I or confirmatory HCV RNA (if anti-HCV antibody tested positive);

6. Vaccination with live vaccines within 4 weeks of the first dose of avelumab and while on trial;

7. Known severe hypersensitivity reactions to monoclonal antibodies (Grade 2: 3 NCI CTCAE v 4.03) or to any component in avelumab's formulation, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma);

8. Known severe hypersensitivity reaction to cisplatin, docetaxel, 5-FU or drugs formulated with polysorbate;

9. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction(< 6 months prior to enrollment), unstable angina, congestive heart failure (2: New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication;

10. Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade> 1 ); however, alopecia, sensory neuropathy Grade :S 2, or other Grade :S 2 not constituting a safety risk based on investigator's judgment are acceptable;

11. Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study;

12. Known alcohol or drug abuse;

13. Prior systemic therapy for gastric cancer;

14. Prior exposure to antibodies directed at PD-1, PD-L 1, CTLA 4 antigens;

15. Pre-existing medical conditions precluding treatment, including any contraindication for major surgery;

16. Pregnancy or lactating mothers. Women of childbearing age must use contraception during and for 3 months following treatment;

17. ECOG performance status of 2 or higher;

18. Significant hearing impairment, as judged by the need for or use of a hearing aid. If there is any uncertainty regarding the degree of hearing impairment, an audiogram will be done. If the audiogram is grossly normal or shows only minor hearing impairment (i.e. not requiring hearing aid), the patient may be enrolled;

19. Unwillingness to undergo investigations and/or treatment as outlined on the study; or

20. Participation to another trial where an investigational drug is being used.

21. History of another malignancy requiring treatment within the last 3 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin treated curatively and in-situ cervical cancer.

Study Design


Intervention

Drug:
mDCF + Avelumab
Patients will receive neoadjuvant therapy consisting of 4 cycles of avelumab added to the modified chemotherapy regimen of docetaxel, cisplatin, 5-fluorouracil (mDCF), followed by surgery and assessment of pathologic response. Then they will receive 4 cycles of adjuvant therapy of mDCF and avelumab.

Locations

Country Name City State
Canada McGill University Health Centre Montréal Quebec

Sponsors (1)

Lead Sponsor Collaborator
McGill University Health Center

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Pathologic Complete Response (pCR) Assessment of the pathologic complete response (pCR) rate after preoperative (neoadjuvant) treatment. pCR has been shown to correlate with long-term outcomes.For the purpose of this study, pCR is considered to represent grade 0 and grade 1 responses, defined by the criteria of the College of American Pathologists. 30±4 weeks
Secondary Two-Year Disease Free Survival (DFS) Analysis of two-year disease-free survival (DFS) following treatment. 104 weeks
Secondary Safety Assessment of Adding Avelumab to mDCF Measurement of the incidence of grade 3 or 4 avelumab-related adverse events following treatment. 104 weeks
See also
  Status Clinical Trial Phase
Recruiting NCT05977998 - A Phase II Study of Perioperative Paclitaxel in Patients With Gastric Adenocarcinoma and Carcinomatosis or Positive Cytology Phase 2
Recruiting NCT05059444 - ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation
Not yet recruiting NCT04931420 - Study Comparing Standard of Care Chemotherapy With/ Without Sequential Cytoreductive Surgery for Patients With Metastatic Foregut Cancer and Undetectable Circulating Tumor-Deoxyribose Nucleic Acid Levels Phase 2
Recruiting NCT03257163 - Pembrolizumab, Capecitabine, and Radiation Therapy in Treating Patients With Mismatch-Repair Deficient and Epstein-Barr Virus Positive Gastric Cancer Phase 2
Completed NCT02128243 - Trial of S-1 Maintenance Therapy in Metastatic Esophagogastric Cancer Phase 2
Completed NCT01178944 - Pralatrexate and Oxaliplatin in Treating Patients With Unresectable or Metastatic Esophageal, Stomach, or Gastroesophageal Junction Cancer Phase 2
Terminated NCT00209079 - Phase II Trial of Gleevec and Taxotere as a Combined Regimen for Advanced Gastric Adenocarcinoma Phase 2
Terminated NCT02862535 - Study to Evaluate the Safety and Tolerability of Andecaliximab as Monotherapy and in Combination With Anti-Cancer Agents in Japanese Participants With Gastric or Gastroesophageal Junction Adenocarcinoma Phase 1
Active, not recruiting NCT05008783 - A Study of AK104 in the First-line Treatment of Locally Advanced Unresectable or Metastatic G/GEJ Adenocarcinoma Phase 3
Recruiting NCT04430738 - Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers Phase 1/Phase 2
Recruiting NCT04114136 - Anti-PD-1 mAb Plus Metabolic Modulator in Solid Tumor Malignancies Phase 2
Completed NCT03196232 - Epacadostat and Pembrolizumab in Treating Patients With Metastatic or Unresectable Gastroesophageal Junction or Gastric Cancer Phase 2
Recruiting NCT04047953 - Paclitaxel (Albumin-bound) Combined With Oxaliplatin and S-1 Conversion Therapy for Gastric Adenocarcinoma N/A
Completed NCT02864381 - Study to Evaluate the Efficacy and Safety of Andecaliximab Combined With Nivolumab Versus Nivolumab Alone in Adults With Unresectable or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Phase 2
Completed NCT02891447 - Heated Mitomycin and Cisplatin During Surgery in Treating Patients With Stomach or Gastroesophageal Cancer Phase 2
Terminated NCT04032704 - A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors Phase 2
Terminated NCT04604132 - Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma Phase 1/Phase 2
Completed NCT02830594 - Pembrolizumab and Palliative Radiation Therapy in Treating Patients With Metastatic Esophagus, Stomach, or Gastroesophageal Junction Cancer Phase 2
Recruiting NCT06038578 - A Study of TRK-950 When Used in Combination With Ramucirumab and Paclitaxel in Patients With Gastric Cancer Phase 2
Terminated NCT04099277 - A Study of LY3435151 in Participants With Solid Tumors Phase 1