Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Stomach Neoplasms

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Esophageal Cancer

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Hematinics

Vitamins

Leucovorin

Fluorouracil

Oxaliplatin

Ramucirumab

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Angiogenesis Inhibitors

Growth Inhibitors

Folate

Vitamin B9

* Oxaliplatin 85 milligrams per square meter (mg/m\^2) given on Day 1 of a 2-week cycle
* Leucovorin 400 mg/m\^2 given on Day 1 of a 2-week cycle
* 5-Fluorouracil (5-FU) 400 mg/m\^2 bolus given on Day 1 of a 2-week cycle
* 5-FU 2400 mg/m\^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle
* Ramucirumab 8 milligrams per kilogram (mg/kg) given on Day 1 of a 2-week cycle

Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met

* Oxaliplatin 85 mg/m\^2 given on Day 1 of a 2-week cycle
* Leucovorin 400 mg/m\^2 given on Day 1 of a 2-week cycle
* 5-FU 400 mg/m\^2 bolus given on Day 1 of a 2-week cycle
* 5-FU 2400 mg/m\^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle
* Placebo given on Day 1 of a 2-week cycle

Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met

Placebo

5-Fluorouracil

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

The purpose of this study is to determine whether ramucirumab when used in conjunction with chemotherapy treatment can help participants with stomach, esophagus, and gastroesophageal cancer.

A Study of Ramucirumab in Participants With Gastric, Esophageal, and Gastroesophageal Cancer

Randomized, Placebo-Controlled, Double-Blind Phase 2 Study of mFOLFOX6 Chemotherapy Plus Ramucirumab Drug Product(IMC-1121B) Versus mFOLFOX6 Plus Placebo for Advanced Adenocarcinoma of the Esophagus, Gastroesophageal Junction or Stomach

Reported are the number of participants who had ramucirumab/placebo-related: AEs, serious AEs (SAEs), AEs based on common terminology criteria for adverse events (CTCAE) ≥Grade 3, AEs = CTCAE Grade 5, as well as, AEs leading to treatment discontinuation and AEs resulting in death. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

PFS was defined using Response Evaluation Criteria in Solid Tumors \[RECIST version (v.) 1.1\] as the time from randomization to the first observation of progressive disease (PD) or death due to any cause, whichever came first. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 millimeters (mm); the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. If a participant did not have a baseline disease assessment, PFS time was censored at the randomization date, regardless of whether or not PD or death was observed. Participants not known to have died or have objective PD were censored at the last post-baseline radiological assessment date.

OS was defined as the time from randomization to death due to any cause. OS was censored at the date of the last follow-up visit for participants who were alive or lost to follow-up.

The percentage of participants who achieved a best overall response of partial response (PR) or complete response (CR) is reported. Response was defined using RECIST, v. 1.1 criteria. CR was the disappearance of all lesions and pathological lymph node reduction in the short axis to \<10 mm. PR was a ≥30% decrease in the sum of the diameters of target lesions. The percentage of participants with objective response=(number of participants whose best overall response achieved was CR or PR/number of participants treated)\*100.

Duration of response was defined using RECIST v. 1.1 criteria as the time from the date criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death from any cause. CR was the disappearance of all lesions and pathological lymph node reduction in the short axis to \<10 mm. PR was a ≥30% decrease in the sum of the diameters of target lesions. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 mm; the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. Participants who were not known to have died and who did not have PD were censored at the date of the last tumor assessment prior to the date of any subsequent systemic anticancer therapy.

TTP was defined using RECIST v. 1.1 as the time from study randomization to the first date of PD. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 mm; the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. TTP was censored at the date of last adequate tumor assessment if death was due to causes other than PD.

Participants with treatment-emergent anti-ramucirumab antibodies were participants with a 4-fold increase (2 dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20).

Eli Lilly and Company

Ramucirumab: 8 mg/kg intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6.

mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle).

* Oxaliplatin: 85 mg/m\^2
* Leucovorin: 400 mg/m\^2
* 5-FU: 400 mg/m\^2 bolus
* 5-FU: 2400 mg/m\^2 continuous given over 46-48 hours

Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.

Ramucirumab and mFOLFOX6

Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6.

mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle).

* Oxaliplatin: 85 mg/m\^2
* Leucovorin: 400 mg/m\^2
* 5-FU: 400 mg/m\^2 bolus
* 5-FU: 2400 mg/m\^2 continuous given over 46-48 hours

Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.

Placebo and mFOLFOX6

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Asian

Native Hawaiian or Other Pacific Islander

Black or African American

White

Race/Ethnicity, Customized

United States

Region of Enrollment

Intent-to-Treat (ITT) Population: all randomized participants.

Chief Medical Officer

ITT population: all randomized participants. Fourteen participants in the Ramucirumab and mFOLFOX6 treatment arm and 15 participants in the Placebo and mFOLFOX6 treatment arm were censored.

Progression-Free Survival (PFS)

ITT population: all randomized participants. Twenty-seven participants in the Ramucirumab and mFOLFOX6 treatment arm and 32 participants in the Placebo and mFOLFOX6 treatment arm were censored.

Overall Survival (OS)

ITT population: all randomized participants.

Percentage of Participants Achieving an Objective Response (Objective Response Rate)

Randomized participants who achieved an objective response of CR or PR. Eight participants in the Ramucirumab and mFOLFOX6 treatment arm and 8 participants in the Placebo and mFOLFOX6 treatment arm were censored.

Duration of Response

ITT population: all randomized participants. Thirty-five participants in the Ramucirumab and mFOLFOX6 treatment arm and 31 participants in the Placebo and mFOLFOX6 treatment arm were censored.

Time to Disease Progression (TTP)

Randomized participants who received any quantity of ramucirumab or placebo, and were evaluated for the presence of anti-ramucirumab antibodies.

Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies

Any Ramucirumab/Placebo-Related AE

Any Ramucirumab/Placebo-Related SAE

Any Ramucirumab/Placebo-Related ≥Grade 3 AE

Any Ramucirumab/Placebo-Related Grade 5 AE

Any AE Leading to Treatment Discontinuation

Any AE with Outcome of Death

Safety population: randomized participants who received any quantity of study drug (Ramucirumab, mFOLFOX6, or placebo).

Number of Participants With Adverse Events (AEs)

Ramucirumab: 8 milligrams per kilogram (mg/kg) intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering modified FOLFOX6 (mFOLFOX6).

mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle).

* Oxaliplatin 85 milligrams per square meter (mg/m\^2)
* Leucovorin 400 mg/m\^2
* 5-Fluorouracil (5-FU) 400 mg/m\^2 bolus
* 5-FU 2400 mg/m\^2 continuous given over 46-48 hours

Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.

Placebo: intravenous infusion administered on Day 1 of each cycle (14 days/cycle). In Cycles 1 and 2, there was a 1-hour observation prior to administering mFOLFOX6.

mFOLFOX6: Administered intravenously per manufacturer's instructions for each drug substance on Day 1 of each cycle (14 days/cycle).

* Oxaliplatin 85 mg/m\^2
* Leucovorin 400 mg/m\^2
* 5-FU 400 mg/m\^2 bolus
* 5-FU 2400 mg/m\^2 continuous given over 46-48 hours

Participants received study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion was met.

Overall Study

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Head and Neck Neoplasms

Esophageal Diseases

Irinotecan

Docetaxel

Tubulin Modulators

Antimitotic Agents

Topoisomerase I Inhibitors

Enzyme Inhibitors

120 mg/m2, IV infusion for 90 minutes on day 1 of each 21 day as a treatment cycle.

Number of Cycles: until progression or unacceptable toxicity develops.

PEP02

300 mg/m2, IV infusion on day 1 of each 21 day as a treatment cycle. Number of Cycles: until progression or unacceptable toxicity develops.

irinotecan

75 mg/m2, IV infusion for 60 minutes on day 1 of each 21 day as a treatment cycle.

Number of Cycles: until progression or unacceptable toxicity develops.

docetaxel

David Cunningham

The purpose of this study is to assess objective tumor response in the single agent treatment of PEP02, irinotecan, or docetaxel for locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma

Palliative chemotherapy has been shown to improve survival compared with best supportive care alone in patients with unresectable or recurrent gastric cancer. There is no standard second-line chemotherapy for advanced gastric cancer and no randomized-controlled trial data suggest a benefit of second-line chemotherapy compared with supportive care alone. Response rates of second-line therapy in phase II trials are similar to those seen for other cancers that are more commonly retreated. Combination therapy may achieve higher response rates than single agents, however, the survival outcome are the same. In addition, data suggest that patients may obtain symptomatic benefits from second-line therapy. In comparison to the toxicity profile of single agent with combination regimen, patients are more tolerable to single agent therapy than combination.

Based on the previous clinical experience in second line chemotherapy of advanced gastric cancer, the single agent of PEP02, irinotecan and docetaxel are selected as the regimens for this randomized phase II study. The efficacy and toxicity outcome of the three-arm design will be a valuable reference for future combination therapy or phase III study design.

Study of PEP02, Irinotecan or Docetaxel in Gastric or Gastroesophageal Junction Adenocarcinoma

A Randomized Phase II Study of PEP02, Irinotecan or Docetaxel as a Second Line Therapy in Patients With Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

PharmaEngine

Simultaneous integrated boost (SIB) used in combination with a fixed dose of radiation (180 cGy in 28 fractions = 5040 Gy PTV dose). Two dose levels (210 cGy and 225 cGy each in 28 fractions) of SIB will be considered in the phase I part of the study, starting at 210 cGy in 28 daily fractions.

For the phase II part of the study once the MTD has been achieved proton therapy will be allowed. Treatment dose will be identical to that of the photon treatment where the PTV is treated to 50.4 Gy(RBE) (RBE=1.1) while the CTV is boosted to 63 Gy(RBE) in 28 fractions.

Chemotherapy Administration: Schedule of chemotherapy, and modifications of chemotherapy drugs during chemoradiation treatment will be at the discretion of the treating medical oncologist per their standard of practice and with consideration to standard chemotherapy drugs in the treatment of esophageal cancer.

Simultaneous integrated boost (SIB) used in combination with a fixed dose of radiation (180 cGy in 28 fractions = 5040 Gy PTV dose). Two dose levels (210 cGy and 225 cGy each in 28 fractions) of SIB will be considered in the phase I part of the study, starting at 210 cGy in 28 daily fractions.

For the phase II part of the study once the MTD has been achieved proton therapy will be allowed. Treatment dose will be identical to that of the photon treatment where the PTV is treated to 50.4 Gy(RBE) (RBE=1.1) while the CTV is boosted to 63 Gy(RBE) in 28 fractions.

Radiation Therapy

James Welsh, MD

The goal of this clinical research study is to find the highest tolerable dose of radiation that can be given in combination with chemotherapy in patients with esophageal cancer that cannot be removed by surgery.

Radiation Therapy:

If you are found to be eligible, you will receive radiation therapy 5 days for 5 weeks. On Week 6, you will receive radiation therapy on 3 days. You will be assigned to a dose level of radiation based on when you join this study. Up to 2 dose levels of radiation will be tested. The first group of participants will receive the lower dose level. The next group will receive a higher dose than the group before it, if no intolerable side effects were seen.

Chemotherapy Administration:

Your medical oncologist and or his/her team will review and discuss all aspects of chemotherapy administration including drugs you will receive, schedule of chemotherapy, and their side effects with you before starting treatment.

Your study doctor may adjust your chemotherapy dose if you experience intolerable side effects.

Study Visits:

You will have weekly study visits while you are receiving radiation therapy. You may have an extra study visit if your doctor thinks it is necessary. At each visit:

* Your complete medical history will be recorded.
* You will have a physical exam, including measurement of your weight and vital signs.
* Your performance status will be recorded.
* You will be asked how you are feeling and about any side effects you may be having.
* Blood ( about 2-3 teaspoons) will be drawn for routine tests.

Length of Study:

You will receive radiation and chemotherapy for up to 6 weeks. You will be taken off study if the disease gets worse or if you experience intolerable side effects.

Visit After the Last Dose:

You will have a study visit 2 weeks (+/- 5 days) after you stop receiving radiation. If you are unable to return to MD Anderson, most of this may be done over the phone. At this visit:

* Your complete medical history will be updated.
* You will be asked how you are feeling and about any side effects that you may be having.
* If the doctor feels it is necessary you will have a physical exam, including measurement of your weight, vital signs, and your performance status will be recorded. If you are unable to travel to this visit, you will not have a physical exam.

Follow-Up Visits:

Your will have follow-up visits after 4 weeks from completing your radiation treatments. Your doctor will decide when you are to return and which tests and procedures will be performed. The following tests and procedures may be performed:

* Your complete medical history may be recorded.
* You may have a physical exam, including measurement of your weight and vital signs.
* You may have a CT or PET scan to check the status of the disease.
* You may be asked how you are feeling and about any side effects you may be having.
* You may have an upper GI endoscopy with biopsies.

If the study doctor thinks it is needed, every year (+/- 2 months), the following tests and procedures will be performed to check the status of the disease:

* You will have a CT or PET/CT scan.
* You may have an upper endoscopy and tumor biopsy.

This is an investigational study. The chemotherapy agents are FDA approved and are commercially available for use in the treatment of esophageal cancer. The higher dose level of radiation in this study is considered investigational.

Up to 42 patients will take part in this study. All will be enrolled at MD Anderson.

Simultaneous Integrated Boost (SIB) in Esophageal Cancer

Phase I/II Study of Evaluating the Safety and Efficacy of Using a Simultaneous Integrated Boost for Dose Escalation in Patients With Esophageal Cancer

MDT defined as CTCAE 3 grade 3 acute radiation toxicity of esophagitis 2 weeks after completion of 6 weeks of radiation therapy.

Local control assessed radiographically using either a PET or CT scan. The one-year local failure rate monitored using the methods of Thall et al.

Complete pathologic response defined as no gross or microscopic tumor in the surgical specimen using light microscopy, but not immunohistochemical stains. Tissue from esophagogastroduodenoscopy can also be used. A partial pathologic response defined as shrinkage in tumor size compared with the original esophagogastroduodenoscopy.

M.D. Anderson Cancer Center

Trastuzumab

Paclitaxel

Albumin-Bound Paclitaxel

Antineoplastic Agents, Immunological

Evorpacept (ALX148) 30 mg/kg Q2W IV, trastuzumab (initial dose of 6 mg/kg followed by 4 mg/kg) Q2W IV, ramucirumab 8 mg/kg Q2W IV, and paclitaxel 80 mg/m2 IV Days 1, 8, and 15 of a 28-day cycle.

Trastuzumab (initial dose of 6 mg/kg followed by 4 mg/kg) Q2W IV, ramucirumab 8 mg/kg Q2W IV, and paclitaxel 80 mg/m2 IV Days 1, 8, and 15 of a 28-day cycle.

Ramucirumab 8 mg/kg Q2W IV and paclitaxel 80 mg/m2 IV Days 1, 8, and 15 of a 28-day cycle.

Evorpacept (ALX148)

Philip Fanning, PhD

Sophia Randolph, MD, PhD

Study Coordinator

A Phase 2/3 Study of Evorpacept (ALX148) in Combination With Trastuzumab, Ramucirumab, and Paclitaxel in Patients With Advanced HER2-overexpressing gastric/GEJ adenocarcinoma.

This is a randomized phase 2 (open-label) / 3 (double-blind), international, multi-center study of patients with metastatic HER2-overexpressing gastric/GEJ adenocarcinoma that has progressed on or after prior HER2-directed therapy and fluoropyrimidine- or platinum-containing chemotherapy and are suitable for chemotherapy (2nd-line or 3rd-line). Approximately 450 adult patients are expected to be enrolled in the study across both phases.

Phase 2 is Open Label; Phase 3 is blinded

A Study of Evorpacept (ALX148) in Patients With Advanced HER2+ Gastric Cancer (ASPEN-06)

A Phase 2/3 Study of Evorpacept (ALX148) in Patients With Advanced HER2-Overexpressing Gastric/Gastroesophageal Junction Adenocarcinoma (ASPEN-06)

Percentage of patients with objective response per RECIST 1.1

ALX Oncology Inc.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Uterine Cervical Neoplasms

Breast Neoplasms

Pancreatic Neoplasms

Glioblastoma

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Anus Neoplasms

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Anal Cancer

Antibodies

Antibodies, Monoclonal

Immunoglobulins

TROP2-directed human monoclonal antibody (Ab) linked to a monomethyl auristatin E (MMAE) prodrug

LCB84

Anti-PD-1 monoclonal antibody

David Browning

Yuan Yuan, MD

DFCI External Referral

Glenn Hanna, MD

Cancer Answer Line

Paul Swiecicki, MD

Douglas Orr, MD

Anjali Raina

Funda Meric-Bernstam, MD

Philippe Bedard, MD

Jennifer Wheler, MD

This is a first-in-human, Phase 1/2 study to evaluate LCB84, a TROP2-directed antibody-drug conjugate, alone and in combination with an anti-PD-1 Ab, in dose escalation (Phase 1) followed by dose expansion (Phase 2).

The study population in dose escalation (Phase 1) consists of patients with advanced solid tumors refractory to standard of care, or for whom no standard of care exists. After the MTD and/or RP2D for single agent LCB84 is determined, dose escalation cohorts with select tumor types will be enrolled. Combination LCB84 and anti-PD-1 Ab will be evaluated in dose escalation after a minimum of 2 dose levels of single agent LCB84 have established DLT safety, to determine the MTD and/or RP2D of combination LCB84 and anti-PD-1 Ab, and to continue into dose expansion cohorts in select tumor types.

A Study to Evaluate TROP2 ADC LCB84 Single Agent and in Combination With an Anti-PD-1 Ab in Advanced Solid Tumors

A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of TROP2-Directed Antibody-Drug Conjugate LCB84, as a Single Agent and in Combination With an Anti-PD-1 Ab, in Patients With Advanced Solid Tumors

Based on tolerability, preliminary anti tumor activity, and pharmacokinetics

Assessed by RECIST 1.1, iRECIST, and RANO-BM

Pharmacokinetic parameters will be determined from observed concentrations of LCB84

Occurrence of ADA measured in serum at selected timepoints during the study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Ramucirumab in Participants With Gastric, Esophageal, and Gastroesophageal Cancer	NCT01246960	Stomach Cancer Esophageal Canc...	Ramucirumab Placebo Oxaliplatin Leucovorin 5-Fluorouracil	18 Years -	Eli Lilly and Company
Study of PEP02, Irinotecan or Docetaxel in Gastric or Gastroesophageal Junction Adenocarcinoma	NCT00813072	Stomach Neoplas... Esophageal Neop...	PEP02 irinotecan docetaxel	18 Years -	PharmaEngine
Simultaneous Integrated Boost (SIB) in Esophageal Cancer	NCT01102088	Esophageal Canc...	Radiation Thera...	18 Years -	M.D. Anderson Cancer Center
A Study of Evorpacept (ALX148) in Patients With Advanced HER2+ Gastric Cancer (ASPEN-06)	NCT05002127	Gastric Cancer Gastroesophagea... Gastric Adenoca...	Evorpacept (ALX... Trastuzumab Ramucirumab Paclitaxel	18 Years -	ALX Oncology Inc.
A Study to Evaluate TROP2 ADC LCB84 Single Agent and in Combination With an Anti-PD-1 Ab in Advanced Solid Tumors	NCT05941507	Advanced Solid ...	LCB84 Anti-PD-1 monoc...	18 Years -	LigaChem Biosciences, Inc.

Spots Global Cancer Trial Database for gastroesophageal