IRX-2, Cyclophosphamide, and Pembrolizumab in Treating Participants With Recurrent or Metastatic Gastric or Gastroesophageal Junction Cancer

NCT03918499 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 18069NCI-2018-01885
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

Brief Summary

This phase Ib/II trial studies the side effects of IRX-2, cyclophosphamide, and pembrolizumab work in treating participants with gastric or gastroesophageal junction cancer that has come back or that has spread to other places in the body. Interleukins, such as those found in IRX-2, are proteins made by white blood cells and other cells in the body and may help regulate immune response. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving RX-2, cyclophosphamide, and pembrolizumab may work better in treating participants with gastric or gastroesophageal junction cancer.

Conditions

Clinical Stage IV Gastric Cancer AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVA Gastric Cancer AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVB Gastric Cancer AJCC v8; Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Pathologic Stage IV Gastric Cancer AJCC v8; Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8; Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Estimated using the product-limit method of Kaplan and Meier. From initial treatment until progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  From first day of study drug administration to disease progression or death, assessed up to 2 years

Secondary Outcomes (2)

• Overall Survival

  Up to 2 years

• Overall Response

  Up to 2 years

Study Arms (1)

Treatment (pembrolizumab, cyclophosphamide, and IRX-2)

EXPERIMENTAL

Participants receive pembrolizumab IV over 30 minutes on day 1. Participants also receive cyclophosphamide IV on day 1 and IRX-2 SC for 10 days starting on day 4 during cycles 1, 5, 9, 13, 17, 21, 25, 29, and 33. Treatment repeats every 3 weeks for up to 35 cycles in the absence of disease or unacceptable toxicity.

Drug: Cyclophosphamide; Biological: Cytokine-based Biologic Agent IRX-2; Biological: Pembrolizumab

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (pembrolizumab, cyclophosphamide, and IRX-2)

Cytokine-based Biologic Agent IRX-2 BIOLOGICAL

Given SC

Also known as: IRX-2

Treatment (pembrolizumab, cyclophosphamide, and IRX-2)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, cyclophosphamide, and IRX-2)

Eligibility Criteria

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

You may qualify if:

• Patients with histologically or cytologically confirmed recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma progressed or intolerant to \>= 2 lines of systemic therapy.
• Patients must have recurrent or metastatic gastric/GEJ adenocarcinoma that are not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
• Willing and able to give informed consent and adhere to protocol therapy; written informed consent and any locally required authorization must be obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
• No prior exposure to PD-1/PD-L 1 inhibitor therapy.
• Patients are deemed eligible for pembrolizumab therapy with tumors demonstrating PD-L1 expression by the Combined Positive Score (CPS) being \>= 1 as per the Food and Drug Administration (FDA)-approved Dako PD-L1 immunohistochemistry (IHC) 22C3 PharmDx assay.
• Eastern Cooperative Oncology Group (ECOG) 0-1.
• Body weight must be \> 30 Kg.
• Hemoglobin \> 8 g/dL.
• Absolute neutrophil count (ANC) \> 1,200 x 10\^9/mL.
• Platelet count \> 75 x 10\^9/mL.
• Serum bilirubin =\< 1.5 x institutional upper limit of normal (ULN) OR direct bilirubin =\< ULN if total bilirubin levels \> 1.5 x ULN.
• Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT/serum glutamate-pyruvate transaminase \[SGPT\]) =\< 5 x ULN.
• Prothrombin time (PT) and partial thromboplastin time (PTT) \< 1.5 x the ULN.
• Serum creatinine =\< 1.5 x ULN OR measured creatinine clearance (CL) \> 40 mL/min or calculated creatinine clearance CL \> 40 mL/min by the Cockcroft-Gault formula or by 24- hour urine collection for determination of creatinine clearance.
• Palliative radiation therapy is allowed to non-target lesions at the discretion of the treating physician.

You may not qualify if:

• Prior exposure to the IRX-2 regimen and/or PD-1/PD-L1 inhibitors are excluded.
• Radiation therapy with a curable intent within 30 days of first dose of study treatment is excluded. However, radiation therapy with a palliative intent is allowed as long as treatment with study medication occurs \>= 14 days after the last dose of radiation.
• Any medical contraindications or previous therapy that would preclude treatment with the IRX-2 regimen or pembrolizumab.
• Known allergies to ciprofloxacin or phytohemagglutin given trace amount of these agents are contained in IRX-2.
• Patients with ongoing chronic myelosuppression, myelodysplasia, or hemorrhagic cystitis which would contraindicate receipt of cyclophosphamide.
• Patients with grade \>= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with IRX-2, pembrolizumab may be included only after consultation with the study physician.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia.
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
• Any chronic skin condition that does not require systemic therapy.
• Patients without active disease in the last 2 years may be included but only after consultation with the study physician.
• Patients with celiac disease controlled by diet alone.
• Current or prior use of immunosuppressive medication within 14 days prior to cycle 1, day 1. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroid or local steroid injections (e.g., intra articular injection).

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Texas Oncology at Baylor Charles A Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

MeSH Terms

Interventions

Cyclophosphamide; IRX 2; pembrolizumab

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-218-5265

Study Officials

• Joseph Chao

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2018
• First Posted: April 17, 2019
• Study Start: April 19, 2019
• Primary Completion: February 9, 2023
• Study Completion: February 9, 2023
• Last Updated: March 23, 2023
• Results First Posted: March 23, 2023

Record last verified: 2023-03

Locations

US (3)