Phase I/II Study of Perioperative Chemotherapy Plus Immunotherapy Followed by Surgery in Localized Esophageal and Gastroesophageal Adenocarcinoma
Phase I/II Study of Perioperative Chemotherapy Plus Immunotherapy Followed by Surgery in Localized Esophageal and Gastroesophageal Adenocarcinoma
To learn if atezolizumab in combination with oxaliplatin and 5-fluorouracil (5-FU), when given before surgery, can help to control esophageal and/or gastroesophageal cancer. To learn if adding tiragolumab to the above drug combination can help to control the disease.
Primary Objectives:
Secondary Objectives:
Inclusion Criteria (cohort 1 and cohort 2)
Signed Informed Consent Form
Age ≥ 18 years at time of signing Informed Consent Form
Ability to comply with the study protocol, in the investigator's judgment
Histologically or cytologically confirmed esophageal or gastroesophageal type I or II adenocarcinoma
No prior therapy including chemotherapy or radiation therapy.
Patients with T1N1, and T2-3 with any N will be eligible.
ECOG Performance Status of 0-1
Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:
Patients with known Gilbert disease: serum bilirubin level ≤ 3 x ULN
Serum creatinine ≤ 1.5 x ULN [or] Creatinine clearance ≥ 70 mL/min (calculated using the Cockcroft-Gault formula)}
Serum albumin ≥ 25 g/L (2.5 g/dL)
For patients not receiving therapeutic anticoagulation: INR and aPTT ≤ 1.5 x ULN
A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 10 slides containing unstained, freshly cut, serial sections should be submitted along with an associated pathology report prior to study enrollment. If <10 slides are available, the patient may still be eligible for the study, after principal investigator approval has been obtained. For Cohort 1: If archival tumor tissue is unavailable or is determined to be unsuitable for required testing, tumor tissue must be obtained from a biopsy performed at screening. Refer to Section 4.5.6 for additional information on tumor specimens collected at screening.
Options for female contraception
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive, and agreement to refrain from donating eggs, as defined below:
Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the last dose of Atezolizumab, 90 days after the final dose of Tiragolumab, 4-9 months after the final dose of oxaliplatin and 6 months after the final dose of 5-FU. Women must refrain from donating eggs during this same period. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state ( 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
Hormonal contraceptive methods must be supplemented by a barrier method. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
Options for contraception in male patients with pregnant female partners and/or with female partners of childbearing potential. "Recommendations related to contraception and pregnancy testing in clinical trials" and the Roche White Paper regarding contraception for males in clinical trials. Atezolizumab +/- Tiragolumab does require male contraception or condom use; guidelines below apply to other protocol-mandated study treatments.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of 1% per year during the treatment period and for for 90 days after the final dose of tiragolumab, 6 months after the final dose of oxaliplatin and 5-FU to avoid exposing the embryo. Men must refrain from donating sperm during this same period.
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
Exclusion Criteria (cohort 1 and cohort 2)
Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
Rash must cover < 10% of body surface area
Disease is well controlled at baseline and requires only low-potency topical corticosteroids
No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months
Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Principal Investigator approval Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.