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Esophagus Cancer, AdenocarcinomaPhase 1/2RiMENCT03995017

Rucaparib Plus Ramucirumab With or Without Nivolumab in Advanced Gastric and Esophageal Adenocarcinoma

A Phase 1/2 study testing Rucaparib, Ramucirumab and Nivolumab in people with Esophagus Cancer, Adenocarcinoma and Stomach Cancer, Adenocarcinoma, run by University of Kansas Medical Center at 8 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The study population is advanced gastric, gastroesophageal, and esophageal adenocarcinoma participants who have failed upfront standard of care chemotherapy. The goal is to demonstrate that Rucaparib plus Ramucirumab with or without Nivolumab has a higher response rate than what has been reported for Ramucirumab in… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Rucaparib, Ramucirumab and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
8 sitesUnited States
Study dates
9 Jan 2020to Dec 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Half of the study population in phase 2 must have a deleterious tumor alteration in at least one protocol specified gene
  • Gastric or gastroesophageal junction adenocarcinoma
  • Advanced stage 4 or locally unresectable stage 3 disease
  • Must have measurable disease
  • Must consent to have a biopsy if archival tissue is not available or not enough for molecular testing
  • Must show evidence of progression or intolerance to at least one previous standard of care systemic therapy (not more than 2 lines of prior therapy)
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  • Patients with human epidermal growth factor receptor 2 (HER2) positive disease must show progression on prior HER2 targeted therapy
  • Toxicities related to prior treatment should be recovered to baseline or less than grade 2 according to CTCAE
  • Adequate organ and marrow function
  • Absence of active autoimmune disease that has required systemic treatment in the past 2 years
  • Absence of conditions requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration. 10mg or less of prednisone or equivalent is acceptable
  • Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients
  • Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence, or to use two forms of adequate contraception prior to study entry, for the duration of study participation, and for 6 months following completion of therapy
  • Men of child-bearing potential must not father a child or donate sperm while on this study and for 7 months after their last study treatment

Who cannot join

  • Prior treatment with a programmed cell death protein 1 (PD1) or programmed death- ligand 1 (PD-L1) inhibitors
  • Prior treatment with poly-(ADP-Ribose)polymerase (PARP)
  • Patients with microsatellite instability (MSI) high or mismatch repair (MMR) deficient tumors
  • Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose
  • Evidence of active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction
  • Inability to swallow tablets
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  • Uncontrollable ascites or pleural effusion
  • Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation
  • Clinically significant hematuria, hematemesis, or hemoptysis, or other history of significant bleeding within 12 weeks
  • Lesions invading any major blood vessels
  • Receipt of the last dose of anticancer therapy less than 28 days prior to the first dose of study drug
  • Major surgery within 8 weeks before first dose of study treatment
  • History of allogenic organ transplantation
  • Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus. Patients with a past or resolved hepatitis B virus (HBV) infection are eligible. Patients positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for hepatitis C virus (HCV) RNA
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of study drug
  • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or serious chronic gastrointestinal conditions
  • Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment
  • Prolonged baseline QT interval corrected for heart rate greater than 470 ms
  • Brain metastases or spinal cord compression. Patients whose brain metastases have been treated may participate provided they show radiographic stability
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
  • Current or anticipated use of other investigational agents while participating in this study
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease before the first dose of investigational product (IP) and of low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or breast feeding

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • KU Cancer Center

    Fairway, Kansas, 66205

  • University of Kansas Cancer Center - CRC

    Fairway, Kansas, 66205

  • University of Kansas Cancer Center - West

    Kansas City, Kansas, 66112

  • The University of Kansas Cancer Center, Westwood Campus

    Kansas City, Kansas, 66205

  • University of Kansas Cancer Center - North

    Kansas City, Missouri, 64154

  • University of Kansas Cancer Center - Lee's Summit

    Lee's Summit, Missouri, 64064

  • University of Kansas Cancer Center - Overland Park

    Overland Park, Kansas, 66210

Other trials in United States

About this study

Official title: A Phase I/II Trial of Rucaparib in Combination With Ramucirumab With or Without Nivolumab in Previously Treated Patients With Advanced Gastric and Esophageal Adenocarcinoma (RiME)

The study population is advanced gastric, gastroesophageal, and esophageal adenocarcinoma participants who have failed upfront standard of care chemotherapy. The goal is to demonstrate that Rucaparib plus Ramucirumab with or without Nivolumab has a higher response rate than what has been reported for Ramucirumab in previously treated patients. Trial will be a phase 1/2 trial. The Phase 1 portion will determine the recommended Phase 2 treatment dose for the combination of Rucaparib plus Ramucirumab and Nivolumab and enroll approximately 6-9 participants. The Phase 2 portion of the study will involve 52 participants allocated between two treatment groups comparing Rucaparib plus Ramucirumab with or without Nivolumab. The participants will be selected based on the results of a screening HRD gene panel.

Being tested
Rucaparib, Ramucirumab, Nivolumab
Medical subject headings
Adenocarcinoma Of Esophagus, Stomach Neoplasms, Adenocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RucaparibDrug

    Also called Rubraca

    Rucaparib tablet

  • RamucirumabDrug

    Also called Cyramza

    Ramucirumab intravenous solution

  • NivolumabDrug

    Also called Opdivo, Bristol- Meyers Squibb (BMS)-936558

    Nivolumab intravenous solution

Study groups in NCT03995017
Study groupRoleWhat they receive
Safety Lead InExperimental* Rucaparib 600 milligrams twice daily * Ramucirumab 8 milligrams per kilogram intravenous every 2 weeks * Nivolumab 480 milligrams intravenous every 4 weeks * Treatment will continue until disease progression, unacceptable toxicity or the patient desires to discontinue this therapy * One dose level decrease of Rucaparib will be planned if toxicity develops in the first 6 patients * 1 cycle= 28 days
Receives: Drug: Rucaparib; Drug: Ramucirumab; Drug: Nivolumab
Cohort AExperimental* Rucaparib 600 milligrams twice daily * Ramucirumab 8 milligrams per kilogram intravenous every 2 weeks * Nivolumab 480 milligrams intravenous every 4 weeks * Treatment will continue until disease progression, unacceptable toxicity or the patient desires to discontinue this therapy * 1 cycle= 28 days
Receives: Drug: Rucaparib; Drug: Ramucirumab; Drug: Nivolumab
Cohort BActive comparator* Rucaparib 600 milligrams twice daily * Ramucirumab 8 milligrams per kilogram intravenous every 2 weeks * Treatment will continue until disease progression, unacceptable toxicity or the patient desires to discontinue this therapy * 1 cycle= 28 days
Receives: Drug: Rucaparib; Drug: Ramucirumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recommended Phase 2 Dose (RP2D)

    Defined as the highest dose studied for which the observed incidence of dose limiting toxicities (DLT) is less than 33%. DLTs will be measured per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: Up to 28 days

  2. Overall Response Rate (ORR)

    Defined as the proportion of participants with overall response to therapy. Overall response is defined as the best response recorded, (including Complete Response (CR) and Partial Response (PR)), from the start of the treatment until the end of treatment. ORR will be measured per the Modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

    Measured: up to 12 months

Secondary outcomes (4)

  1. Number of participants with treatment related adverse events (TRAEs)

    Determining per CTCAE 5.0

    Measured: Up to 12 months

  2. Overall Benefit Rate (OBR)

    Defined as the proportion of participants with overall benefit to therapy. Overall benefit is defined as the best response recorded, (including complete Response (CR), Partial Response (PR), and Stable Disease (SD)), from the start of the treatment until the end of treatment. Determine overall benefit of therapy using modified RECIST version 1.1

    Measured: Up to 12 months

  3. Progression free survival (PFS)

    Reported as the proportion of participants that achieve PFS. PFS is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever occurs first. Measured per modified RECIST version 1.1

    Measured: Up to 12 months

  4. Overall survival (OS)

    Defined as the time from the start of treatment until death due to any cause, reported as the mean of all participants' OS. Measured per the medical record.

    Measured: Up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jun 2019
  2. Study start9 Jan 2020
  3. Primary completion19 Oct 2022
  4. Study completionDec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Phase 1 - Safety Lead In - Enroll 6-9 molecularly unselected participants to determine the safety of the triplet combination of Rucaparib plus Ramucirumab and Nivolumab. One level dose de-escalation of Rucaparib will be planned based on dose limiting toxicity (DLT) signal of the first 6 participants run in phase. Phase 2 - Parallel - Enroll 52 participants (26 in each cohort), open label, two treatment cohorts design evaluating Rucaparib plus Ramucirumab with or without Nivolumab. 50 percent (%) of participants enrollment to each treatment cohort will represent molecularly unselected population and the remaining 50% will be selected based on integrated screening tumor Homologous Recombination Deficiency (HRD) gene panel. The primary objective is efficacy by measuring the Overall Response Rate (ORR).
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03995017
Sponsor's protocol ID
IIT-2018-RucaRamNivo
Acronym
RiME
Status last verified
Jan 2023
First submitted
19 Jun 2019
Last updated
1 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Rucaparib, Ramucirumab and Nivolumab in people with Esophagus Cancer, Adenocarcinoma and Stomach Cancer, Adenocarcinoma, run by University of Kansas Medical Center at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 1 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended Phase 2 Dose (RP2D) (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03995017.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2023.

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