Blood and Lymph Conditions

All Conditions

Neoplasms

Digestive System Diseases

Thrombocytopenia

Gastrointestinal Neoplasms

Digestive System Neoplasms

Blood Platelet Disorders

Hematologic Diseases

Cytopenia

Gastrointestinal Diseases

All Drugs and Chemicals

Maleic acid

Enzyme Inhibitors

30 participants will be randomized into a 1:1 fashion and will be stratified based on the number of cytotoxic agents in the patient's chemotherapy regimen. Participants will complete study procedures as outlined:

Lead-In Period (Day 1 - 15)

* Pre-determined dose of Avatrombopag 1x daily.
* Participants failing to achieve a platelet count ≥100,000/µL within 2 weeks will be considered a treatment failure (and will proceed to the end-of-study visit).

On-Cycle Period (Day 15 - up to Week 6)

• Pre-determined dose of Avatrombopag 1x daily.

Follow-up Period

* End of Treatment on-site visit.
* Follow-up visit 30-42 days after End of Treatment visit.

30 participants will be randomized into a 1:1 fashion and will be stratified based on the number of cytotoxic agents in the patient's chemotherapy regimen. Participants will complete study procedures as outlined:

Lead-In Period (Day 1 - 15)

* Pre-determined dose of matching placebo 1x daily.
* Participants failing to achieve a platelet count ≥100,000/µL within 2 weeks will be considered a treatment failure (and will proceed to the end-of-study visit).

On-Cycle Period (Day 15 - up to Week 6)

• Pre-determined dose of matching placebo 1x daily.

Follow-up Period

* End of Treatment on-site visit.
* Follow-up visit 30-42 days after End of Treatment visit.

Thrombopoietin receptor agonist, tablet taken orally.

Avatrombopag

Lactose monohydrate, tablet taken orally.

Matching Placebo

Hanny Al-Samkari, MD

Gerald Soff, MD

Stephen Lattanzi, M.D.

Gerald A Soff, MD

Kanika Nair, M.D.

Joseph Shatzel, M.D.

Sandhya Panch, M.D.

The purpose of this study is to compare the efficacy of two study drugs, Avatrobopag versus placebo, to treat persistent Chemotherapy-Induced Thrombocytopenia (CIT) in patients with gastrointestinal (GI) malignancies receiving cytotoxic chemotherapy.

The names of the study drugs involved in this study are:

* Avatrombopag (a thrombopoietin receptor agonist)
* Matching placebo

This is a randomized, double-blinded, placebo-controlled, multicenter phase 2 clinical trial evaluating Avatrombopag versus placebo for Chemotherapy-Induced Thrombocytopenia (CIT) in patients with gastrointestinal (GI) malignancies. Avatrombopag may increase or stimulate megakaryocytes, which aid in producing blood platelets, resulting in an increased production of platelets.

* Participants will be "randomized" into one of the study groups: Group A: Avatrombopag or Group B: Matching placebo. Randomization means that a participant is put into a group by chance.
* All patients who complete the study (whether they received avatrombopag or placebo) have the opportunity to receive avatrombopag to treat CIT through a special free drug program available only to the participants of this study.

The U.S. Food and Drug Administration (FDA) has not approved avatrombopag for CIT, but it has been approved for other uses.

Study procedures include screening for eligibility, treatment visits, and blood tests.

Participants will receive the study treatment or placebo for up to seven weeks and will be followed for up to 42 days after the last dose.

It is expected that about 60 people will take part in this research study.

Swedish Orphan Biovitrum (Sobi), biopharmaceutical company, is supporting this research study by providing the study drugs and funding.

Avatrombopag vs. Placebo for CIT in GI Malignancies

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Avatrombopag for Persistent Chemotherapy-Induced Thrombocytopenia in Patients With Gastrointestinal Malignancies (ACT-GI)

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

The primary endpoint of this study is the comparison of the response rate between the avatrombopag arm and the placebo arm. A response is defined as achieving a platelet count ≥100,000/µL within the 2 week lead-in period and then finishing at least 1 cycle of chemotherapy without CIT recurrence (no on-cycle dose-reduction or treatment delay due to thrombocytopenia and ability to receive another cycle of chemotherapy without dose-reduction or treatment delay, defined as platelet count of ≥100,000/µL at the start of the following cycle whether or not an additional cycle is planned).

Defined as the composite of successful initial platelet count recovery to ≥100,000/µL within 15 days of initiation of study drug, plus CIT prevention for one additional chemotherapy cycle (including at the completion of that cycle/start of the following cycle).

Assessed by the rate of initial platelet count recovery to ≥100,000/µL during the lead-in period

Assessed by the rate of initial platelet count recovery to ≥100,000/µL during the lead-in period.

The decision on platelet transfusion could be made either because the patient's platelet count is below a threshold, or due to physician's decision. The probability of patients requiring platelet transfusion will be estimated with a 95% confidence interval.

The rate of clinically relevant bleeding will be estimated by the Kaplan-Meier curve. Bleeding events will be graded according to CTCAE and according to the modified WHO bleeding scale. Clinically significant bleeding events will be considered grade II-IV events per this scale.

Thromboembolic events will be graded per CTCAE.

Swedish Orphan Biovitrum

Principal Investigator

Pharmaceutical Solutions

Lurbinectedin will be administered intravenously (IV) as a 1-hour (±10 min) infusion on Day 1 of each cycle (one cycle = 3 weeks ± 48 hours).

Lurbinectedin will be administered with a minimum total volume of 100 mL of solution for infusion (either on 5% glucose or 0.9% sodium chloride).

Lurbinectedin will be administered intravenously through peripheral or central lines at a dose of 3.2 mg/m2 at a fixed infusion rate.

Lurbinectedin 4 MG Injection [Zepzelca]

Erkut Borazanci, MD

Clinical Trials Nurse Navigator

The purpose of this research is to evaluate the activity and safety of lurbinectedin in adult patients with advanced Gastrointestinal Malignancies with DNA repair mutations.

Lurbinectedin in Patients With Advanced Gastrointestinal Malignancies With DNA Repair Mutations

A Phase II Pilot Clinical Trial of Lurbinectedin (Zepzelca™ PM01183) in Patients With Gastrointestinal Malignancies With DNA Repair Mutations

To evaluate the antitumor activity of Lurbinectedin in terms of overall response rate (ORR), according to RECIST v.1.1, in patients with advanced pancreatic cancer with DNA repair mutations.

Duration of response (DOR), defined as the time from the date when the response criteria (PR or CR) are fulfilled to the date of PD, recurrence or death.

Clinical benefit, defined as the percentage of patients with ORR or SD ≥4 months, according to RECIST v.1.1.

Measure amount of CA19-9, CEA, or CA125 (whichever is being followed) in blood during treatment.

Progression-free survival (PFS), defined as the time from the date of first infusion to the date of PD, death (of any cause), or last tumor evaluation.

Progression-free survival rate at three months (PFS3), defined as the percentage of patients who are alive and progression-free three months after the first infusion.

Overall survival (OS), defined as the time from the date of first infusion to the date of death (of any cause) or last patient contact.

Overall survival rate at six months (OS6), defined as the percentage of patients who were alive six months after the first infusion

Overall survival rate at 12 months (OS12), defined as the percentage of patients who were alive 12 months after the first infusion

Treatment safety: AEs, serious AEs (SAEs) and laboratory abnormalities graded according to the NCI-CTCAE v.5

Jazz Pharmaceuticals

HonorHealth Research Institute

* Quality of life assessments will be collected using The Functional Assessment of Cancer Therapy- Colorectal
* Blood for circulating tumor DNA will be collected

The Functional Assessment of Cancer Therapy- Colorectal (FACT-C) questionnaire measures health-related quality of life for people with chronic illnesses.

The Functional Assessment of Cancer Therapy- Colorectal

Theodore S Hong, MD

In this research study, the investigators are looking to see if the circulating tumor DNA (genetic material), also known as ctDNA, in the blood will help them predict whether the participant's cancer will come back.

In this research study, the investigator are performing blood draws to see if the presence or absence of circulating tumor DNA (ctDNA), the genetic material in the participant's cancer's cells, will help the investigators predict whether the participant's cancer will come back or not.

A Study of the Role of Circulating Tumor DNA in Predicting the Likelihood of Organ Preservation After Clinical Complete Response to Neoadjuvant Therapy for Rectal Cancer

Local recurrence will be defined as recurrence of the pathologically confirmed adenocarcinoma. This may be detected by endoscopy for intraluminal recurrence or after radical surgery for radiographic evidence of extraluminal/mesorectal recurrence. The recurrence must be in the peri-anastomic site or rectal stump, or pre-sacral area. Regional nodal recurrence and lateral pelvic lymph node recurrence of rectal cancer are also included in this definition.

European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) for Colorectal cancer(CR) 29 item questionnaire. The survey will be given at baseline, 6, 12, and 24 months. Results will be reported as the median score for each question. A score of 1 represents 'Not at All' and 4 represents 'Very Much'.

The SF-12 is a 12 item validated questionnaire that assesses a participants view of their health. Scores will be normalized on a 100 point scale with higher scores representing better health.

The Low Anterior Resection Syndrome (LARS) Score is used to assess bowel dysfunction. The survey is assessed on a scale of 0-42 points, with a higher score indicating worse bowel dysfunction.

Fecal Incontinence Quality of Life (FIQOL) Score. Lower scores represent lower functional status.

The FISI measures incontinence for gas, mucus, liquid stool,and solid stool. The survey assesses the number of times per day that the participant experiences incontinence for gas, mucus, liquid stool,and solid stool. Higher scores represent a higher degree of fecal incontinence.

Clinical Genomics

Massachusetts General Hospital

Rare Diseases

Cholangiocarcinoma

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Antineoplastic Agents

Amino Acids

Ceritinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Phase II, single-arm study of oral ceritinib in adult patients with ALK and ROS1 activated gastrointestinal malignancies

Treatment with ceritinib will continue until patient experiences unacceptable toxicity that precludes further treatment, discontinues treatment at the discretion of the investigator or patient, starts a new anticancer therapy and/or dies.

ceritinib

Christopher Lieu, MD

The available data indicate that Ceritinib has substantial anti-tumor activity in patients with anaplastic lymphoma kinase (ALK) and ROS1 rearranged non-small cell lung cancer (NSCLC). This trial will investigate the potential of Ceritinib in patients with advanced gastrointestinal malignancies with ALK and ROA1 rearrangement, and for whom there is no available therapeutic option.

This is a single-arm, open-label, multicenter, phase II study of ceritinib in adult patients with ALK- and ROS1 activated colorectal, cholangiocarcinoma, pancreatic, hepatic, gastric, or esophageal adenocarcinoma. An estimated 500 patients will be screened for ALK and ROS1 by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) per institutional standard of care (SOC), and/or ALK/ROS1 by next-generation sequencing (NGS). At least 30 identified patients will be treated with ceritinib per protocol. Treatment with ceritinib will continue until patient experiences unacceptable toxicity that precludes further treatment, discontinues treatment at the discretion of the investigator or patient, starts a new anticancer therapy and/or dies.

Male and female patients aged 18 or over that have colorectal adenocarcinoma, cholangiocarcinoma, pancreatic, hepatocellular, gastric or esophageal adenocarcinoma that contain an activated ALK gene due to rearrangement, mutation, amplification, translocation or other mechanisms. Patients must have been pretreated with cytotoxic chemotherapy.

Study of Oral Ceritinib in Patients With ALK and ROS1 Activated Gastrointestinal Malignancies

A Phase II, Multicenter, Single-Arm Study of Oral Ceritinib in Adult Patients With ALK and ROS1 Activated Gastrointestinal Malignancies

Antitumor activity of ceritinib will be based on the best overall response. Response rate (complete response \[CR\], partial response \[PR\], CR + PR) will be tabulated.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Avatrombopag vs. Placebo for CIT in GI Malignancies	NCT05772546	Gastrointestina... Gastrointestina... Chemotherapy-In...	Avatrombopag Matching Placeb...	18 Years -	Massachusetts General Hospital
Avatrombopag vs. Placebo for CIT in GI Malignancies	NCT05772546	Gastrointestina... Gastrointestina... Chemotherapy-In...	Avatrombopag Matching Placeb...	18 Years -	Massachusetts General Hospital
Lurbinectedin in Patients With Advanced Gastrointestinal Malignancies With DNA Repair Mutations	NCT05229588	Gastrointestina...	Lurbinectedin 4...	18 Years -	HonorHealth Research Institute
A Study of the Role of Circulating Tumor DNA in Predicting the Likelihood of Organ Preservation After Clinical Complete Response to Neoadjuvant Therapy for Rectal Cancer	NCT03749083	Gastrointestina...	The Functional ...	18 Years -	Massachusetts General Hospital
Study of Oral Ceritinib in Patients With ALK and ROS1 Activated Gastrointestinal Malignancies	NCT02638909	Colorectal Aden... Cholangiocarcin... Pancreatic Aden... Hepatocellular ... Gastric Adenoca... Esophageal Aden...	ceritinib	18 Years -	Criterium, Inc.
Avatrombopag vs. Placebo for CIT in GI Malignancies	NCT05772546	Gastrointestina... Gastrointestina... Chemotherapy-In...	Avatrombopag Matching Placeb...	18 Years -	Massachusetts General Hospital

Spots Global Cancer Trial Database for gastrointestinal malignancies