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Clinical Trial 21790

Cancer Type: Gastrointestinal Tumor
Study Type: Treatment
NCT#: NCT05058651

Phase: Phase II/III
Principal Investigator: Haider, Mintallah

Call 813-745-6100
or 1-800-679-0775 Learn More

Overview

Study Title

Randomized Phase II/III Trial of First Line Platinum/Etoposide with or without Atezolizumab (NSC #783608) in Patients with Advanced or Metastatic Poorly Differentiated Extrapulmonary Neuroendocrine Carcinomas (NEC)

Summary

This phase II/III trial compares the effect of immunotherapy with atezolizumab in combination with standard chemotherapy with a platinum drug (cisplatin or carboplatin) and etoposide versus standard therapy alone for the treatment of poorly differentiated extrapulmonary (originated outside the lung) neuroendocrine cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). The other aim of this trial is to compare using atezolizumab just at the beginning of treatment versus continuing it beyond the initial treatment. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cisplatin and carboplatin are in a class of medications known as platinum-containing compounds that work by killing, stopping or slowing the growth of cancer cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair, and it may kill cancer cells. Giving atezolizumab in combination with a platinum drug (cisplatin or carboplatin) and etoposide may work better in treating patients with poorly differentiated extrapulmonary neuroendocrine cancer compared to standard therapy with a platinum drug (cisplatin or carboplatin) and etoposide alone.

Objective

Primary Objectives Among patients with metastatic extrapulmonary poorly differentiated small cell NEC, to compare overall survival (OS, measured from randomization) in a fixed sequence as follows: a. Compare the combination of induction platinum/etoposide and atezolizumab followed by maintenance atezolizumab (Arm 1) versus induction platinum/etoposide alone (Arm 3) b. Compare the combination of induction platinum/etoposide and atezolizumab followed by observation (Arm 2) versus induction platinum/etoposide alone (Arm 3) c. Compare the combination of induction platinum/etoposide & atezolizumab followed by maintenance atezolizumab (Arm 1) vs the combination of induction platinum/etoposide and atezolizumab followed by observation (Arm 2) Secondary Objective(s): a. To compare OS, measured from start of observation/maintenance, across arms b. To compare progression free survival (PFS) (measured from randomization and measured from start of observation/maintenance) across arms c. To compare objective response rate (ORR = confirmed and unconfirmed partial response (PR) + confirmed and unconfirmed complete response (CR)) across arms among patients with measurable disease at randomization d. To compare clinical benefit rate (CBR = confirmed and unconfirmed PR + confirmed and unconfirmed CR + stable disease (SD)) across arms among patients with measurable disease at randomization e. To compare duration of response (DOR) across arms f. To evaluate the safety and tolerability of each arm Additional Objective: a. To bank tumor and blood samples for future biomarker correlative studies

Treatments

Therapies

Chemotherapy (NOS); Immunotherapy

Medications

Atezolizumab (Tecentriq); Etoposide (); Paraplatin (carboplatin); carboplatin (); cisplatin (); etoposide ()

Inclusion Criteria

Participants must have histologically-confirmed (local site pathological confirmation sufficient) extrapulmonary poorly differentiated, neuroendocrine carcinoma (NEC) that is unresectable or metastatic and not eligible for definitive therapy as deemed per the treating investigator

Participants must have radiologically evaluable disease, measurable or non-measurable, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. All measurable and non-measurable lesions must be assessed by CT scan with IV contrast within 28 days prior to registration. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form

Participants must have brain MRI (or CT head with contrast if there is contraindication to MRI brain) if clinically indicated within 28 days prior to registration. Note: Brain imaging is not required in participants without known and/or clinical concern for brain metastases. Participants with asymptomatic central nervous system (CNS) metastases are eligible if one or more of the following apply:

a. Participants who have received treatment for brain metastases must have:

1. No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration

2. Discontinued all corticosteroids at least 14 days prior to registration

b. Participants with treatment-naive brain lesions must have:

1. No lesion measuring > 2.0 cm in size in any axis

2. MRI brain or CT head with contrast (if there is contraindication to MRI brain) demonstrating no evidence for mass effect, edema, or other impending neurological compromise within 28 days prior to registration

3. No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration

4. No need for > 2 mg of dexamethasone (or equivalent of > 10 mg prednisone) per day at time of registration

Participants with prior history of non-metastatic (localized/locally advanced disease) extrapulmonary poorly differentiated NEC may have had prior platinum-based therapy +/- radiation +/- surgery provided that all therapy was completed >= 6 months prior to registration

Participants must discontinue denosumab prior to study registration and plan to replace with a bisphosphonate while on the study

Participants must be >= 18 years of age

Participants must have a Zubrod performance status of => Participants must have a complete medical history and physical exam within 28 days prior to registration

Additional criteria will apply

Exclusion Criteria

Participants must not have symptomatic central nervous system (CNS) metastases

Participants must not have known or suspected leptomeningeal disease

Participants must not have had prior treatment for advanced or metastatic NEC EXCEPT one cycle of platinum (carboplatin/cisplatin) + etoposide is allowed prior to registration. Other chemotherapy regimens are not allowed. For participants with prostate or urothelial NEC, prior chemotherapy for the non-NEC component (e.g. adenocarcinoma or urothelial) is allowed as long as such therapy was completed >= 24 weeks prior to registration and participants have recovered from all prior toxicities to => Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, CD137 agonists, anti-CTLA-4 agent, or any other immune checkpoint inhibitors for any neuroendocrine neoplasm. Immune checkpoint inhibitors given for other cancer indications are allowed provided last therapy was given at least 12 months prior to study registration

Participants must not have received treatment with systemic immunostimulatory agents including, but not limited to, interferon and interleukin2 [IL-2] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to registration

Participants must not have had history of known severe allergy, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, including to Chinese hamster ovary cell products or to any component of the atezolizumab formulation, cisplatin, carboplatin, or etoposide

Participants must not be on active systemic therapy for another cancer with the exception of hormonal therapy including androgen deprivation therapy (e.g., gonadotropin-releasing hormone [GnRH] agonists or antagonists), which can be continued while participants are receiving protocol therapy. Use of enzalutamide or apalutamide is permitted after completion of chemotherapy and must be held during chemotherapy for participants receiving prior to enrollment. Use of darolutamide is permitted during chemotherapy. Glucocorticoid-containing regimens, including abiraterone, are not permitted.

Participants must not have uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN) within 14 days prior to registration. Participants who have asymptomatic hypercalcemia are eligible provided that medical therapy to treat the hypercalcemia is planned

Participants must not have a diagnosis of immunodeficiency nor be receiving systemic steroid therapy (equivalent of > 20 mg of hydrocortisone per day) or any other form of immunosuppressive therapy within 14 days prior to registration

Participants must not have active or history of autoimmune disease or immune deficiency, including, but not limited to myasthesia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener grandulomatosis, Sjogren syndrome, Guillian-Barre syndrome, or multiple sclerosis

Additional Criteria will apply

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