Pembrolizumab, Combination Chemotherapy, and Radiation Therapy Before Surgery in Treating Adult Patients With Locally Advanced Gastroesophageal Junction or Gastric Cardia Cancer That Can Be Removed by Surgery

• Register: ClinicalTrials.gov
• Last refreshed on: 29 April 2024
• Main ID: NCT02730546
• Date of registration: 01/04/2016
• Prospective Registration: Yes
• Primary sponsor: Mayo Clinic
• Public title: Pembrolizumab, Combination Chemotherapy, and Radiation Therapy Before Surgery in Treating Adult Patients With Locally Advanced Gastroesophageal Junction or Gastric Cardia Cancer That Can Be Removed by Surgery
• Scientific title: Phase 1b/2 Clinical Trial of Neoadjuvant Pembrolizumab Plus Concurrent Chemoradiotherapy With Weekly Carboplatin and Paclitaxel in Adult Patients With Resectable, Locally Advanced Adenocarcinoma of the Gastroesophageal Junction or Gastric Cardia
• Date of first enrolment: June 24, 2016
• Target sample size: 31
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02730546
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Harry H. Yoon, M.D.
• Affiliation: Mayo Clinic

Key inclusion & exclusion criteria

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma involving the
gastroesophageal junction or gastric cardia

- Central pathology review to determine evaluability of archived
esophagogastroduodenoscopy (EGD)/biopsy sample

- NOTE: If archived sample was collected > 8 weeks prior to pre-registration (reg),
is not available in a timely manner, or was collected outside of Mayo Clinic and
considered unevaluable, then baseline EGD with primary tumor biopsy at Mayo
Clinic must be performed unless clinically contraindicated; patient is allowed to
enroll regardless of whether this Mayo Clinic tissue sample is evaluable; (Only 1
EGD with primary tumor biopsy performed at Mayo Clinic =< 8 weeks prior to
pre-reg is required)

- NOTE: For both archival or newly obtained tissue, only biopsies are adequate
(fine needle aspiration [FNA] is not adequate)

- Willing to provide mandatory tissue samples for research purposes

- Baseline imaging with an fludeoxyglucose (FDG)-positron emission tomography (PET) scan
negative for distant metastatic disease must be obtained =< 28 days prior to
registration

- Surgically resectable (T2N0, T3N0, Tany with node positivity, M0), as determined by
endoscopic ultrasound (EUS) and the following minimum diagnostic work-up:

- Whole-body PET/computed tomography (CT) (PET/CT of skull base to mid-thigh is
acceptable)

- EUS =< 21 days prior to registration

- NOTE: Patients may have regional adenopathy including para-esophageal, gastric,
gastrohepatic and celiac nodes; if celiac adenopathy is present, it must be < 2
cm

- NOTE: If patient unable to have PET/CT then CT chest/abdomen/pelvis with contrast
(preferred) or MRI chest/abdomen/pelvis with contrast

- Surgical consultation at enrolling site to confirm that patient will be able to
undergo curative resection after completion of chemoradiation =< 56 days prior to
registration

- Tumor is amenable to standard resection and reconstruction

- Radiation oncology consultation at enrolling site to confirm that disease can be
encompassed in a radiotherapy field =< 56 days prior to registration

- NOTE: Radiotherapy quality assurance rapid review must be performed before the
first fraction of radiation therapy (RT) is administered; if RT constraints
cannot be met, the patient will be removed from the protocol prior to treatment

- Consultation with a medical oncologist at enrolling site =< 56 days prior to
registration, with determination that treatment with neoadjuvant chemoradiotherapy
with weekly carboplatin and paclitaxel is considered acceptable

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

- Adequate oral intake and nutritional status without current or likely need for enteral
or parenteral feeding during chemoradiation or the preoperative period

- Pre-treatment pulmonary function tests (PFTs), collected =< 90 days prior to
enrollment, must show forced expiratory volume in one second (FEV1) > 60% of predicted

- Adequate organ function =< 21 days prior to registration:

- Aspartate transaminase (AST) level =< 2.5 x upper limit of normal (ULN) and
alanine transaminase (ALT) =< 3 x upper limit of normal (ULN)

- Total bilirubin level of =< 1.5 x ULN

- Creatinine level =< 1.2 x ULN or creatinine clearance > 60 mL/min/1.73 m^2 for
patients with creatinine levels above or below the institutional normal

- Hemoglobin (Hgb) >= 9 g/dl without transfusion or epoetin dependency (=< 7 days
prior to assessment)

- Absolute neutrophil count >= 1.5 x 10^9/L

- Platelets >= 100 x 10^9/L

- Albumin >= 2.5 g/dl

- Female patients of childbearing potential must be willing to use 2 methods of birth
control or be surgically sterile, or abstain from heterosexual activity for the course
of the study through 120 days after the last dose of study medication

- NOTE: Patients of childbearing potential are those who have not been surgically
sterilized or have not been free from menses for > 1 year

- Female patients of childbearing potential must have a negative urine or serum
pregnancy test =< 7 days prior to registration

- NOTE: If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required

- Male patients must agree to use an adequate method of contraception starting with the
first dose of study therapy through 120 days after the last dose of study therapy

- NOTE: Abstinence is acceptable if this is the established and preferred method of
contraception for the subject

- Provide signed written informed consent

- Willing to return to enrolling institution for follow-up

- Willing to provide mandatory tissue and blood samples for research purposes

- NOTE: Patients must be willing to provide at the time surgical resection; for
patients who do not undergo surgery, any on-study tumor biopsy obtained for
clinical purposes subsequent to the baseline biopsy must also be available for
analysis

Exclusion Criteria:

- Tumor characteristics - any of the following are excluded:

- Evidence of distant metastases

- Tumors whose location is restricted to the tubular esophagus (i.e., without
involvement of the GEJ or cardia)

- Tumors whose proximal end are at the level of the carina or higher

- Invasion of the tracheobronchial tree or presence of tracheoesophageal fistula

- Palpable supraclavicular nodes, biopsy-proven involvement of supraclavicular
nodes, or radiographically involved supraclavicular nodes (> 1.5 cm in greatest
dimension)

- T1N0M0, T4Nany, or in situ carcinoma

- Tumor must not extend 5 or more cm into the stomach

- Received prior treatment or receiving current treatment for this malignancy

- Prior radiation to chest or abdomen, or to > 30% of the marrow cavity

- Inadequate caloric or fluid intake whereby there is a current or likely future need
for enteral or parenteral feeding during chemoradiation or the preoperative period

- Major surgery =< 4 weeks prior to registration

- Active autoimmune disorders, including patients known to be human immunodeficiency
virus


Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Stage IB Gastric Cancer AJCC v7

Stage II Gastric Cancer AJCC v7

Gastroesophageal Junction Adenocarcinoma

Stage IIA Gastric Cancer AJCC v7

Stage IIIA Gastric Cancer AJCC v7

Gastric Cardia Adenocarcinoma

Stage IIIB Gastric Cancer AJCC v7

Stage IIB Gastric Cancer AJCC v7

Intervention(s)

Other: Laboratory Biomarker Analysis

Radiation: Radiation Therapy

Drug: Fluorouracil

Drug: Leucovorin Calcium

Drug: Oxaliplatin

Procedure: Therapeutic Conventional Surgery

Drug: Carboplatin

Biological: Pembrolizumab

Drug: Paclitaxel

Procedure: Computed Tomography

Procedure: Positron Emission Tomography

Primary Outcome(s)

Pathological Complete Response (PathCR) Rate [Time Frame: Up to 3 years]

Secondary Outcome(s)

Incidence of Dose-limiting Toxicities (DLTs) Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [Time Frame: Up to 3 years]

Progression-free Survival (PFS) [Time Frame: Time from the date of study registration to the date of death due to all causes, recurrences if R0 resections are achieved, progression disease before undergoing surgery, or R1/R2 resection at surgery, whichever comes first, assessed up to 3 years]

Overall Survival (OS) [Time Frame: Time from the date of study registration to the date of death due to all causes, assessed up to 3 years]

Complete Resection With no Tumor Within 1 mm of the Resection Margins (R0) Rate [Time Frame: Up to 3 years]

Time to Relapse (TTR) [Time Frame: Time from the date of study registration to the date of 1st documented relapse/recurrence among patients who achieve R- resection, assessed up to 3 years]

Disease-free Survival (DFS) [Time Frame: Time from the date of study registration to the date of death due to all causes or recurrence, whichever occurs first, among patients who achieved an R0 resection, assessed up to 3 years]

Secondary ID(s)

15-005311

MC1541

NCI-2016-00508

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)

Results

• Results available: Yes
• Date Posted: 25/08/2022
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02730546