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Neoadjuvant Intra-tumoral RP2 and FLOT in Gastroesophageal Adenocarcinoma

ConditionsGastric AdenocarcinomaEsophageal AdenocarcinomaGastroesophageal Junction Adenocarcinoma
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAbramson Cancer Center at Penn Medicine

About this trial

The research study is being conducted to study whether performing injections of a new treatment, called RP2, directly into stomach and esophagus tumors along with standard chemotherapy (called FLOT) is safe and whether it does a better job of killing cancer before surgery compared to chemotherapy alone.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients must have histologically confirmed and clinically staged T2 or higher or node positive, non-metastatic esophageal, gastroesophageal junction, or gastric adenocarcinoma.

Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.

Patents must be deemed a surgical candidate by a thoracic surgeon, surgical oncologist, or surgeon who is qualified to perform the appropriate surgical procedure based on patient's primary tumor site.

Absolute neutrophil count (ANC) ≥ 1,500/microliter

Disqualifiers

Has received prior chemotherapy, radiation therapy, or immunotherapy (anti-programmed cell death protein-1 (PD-1), anti-programmed death ligand-1 (PD-L1), or anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) for the current malignancy.

Per the investigator, has contraindications to receiving chemotherapy with FLOT.

Per the sub-investigator (gastroenterologist) responsible for intra-tumoral injections or the investigator, patient has contraindications to repeated upper endoscopy for intra-tumoral injections. These could include medical conditions that would, per the judgment of the sub-investigator or investigator, inappropriately increase the risk of upper endoscopy.

Conditions in which anticoagulant therapies cannot be safely stopped in the periprocedural period or patients on warfarin with a target international normalized ratio (INR) ≥ 2.5 that cannot be temporarily reversed to INR ≤ 1.7.

Trial design

Design model

Single group

Treatments tested in this trial

  • RP2

    Biological/Vaccine

    Upper endoscopy with RP2 intra-tumoral injection of 1 x 10(6) plaque forming units (PFU)/mL for first intra-tumoral injection, up to 10mL of 1x107 PFU/mL of RP2 for subsequent intra-tumoral injections. Injection will occur within 4 days prior of each cycle FLOT.

  • 5-Fluorouracil

    Combination product

    5-Fluorouracil as part of the FLOT regimen 2,600mg/m2 intravenous infusion over 24 hours on day 1 of each 14-day cycle for 4 cycles.

  • Leucovorin

    Combination product

    Leucovorin as part of the FLOT regimen 200mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.

  • Oxaliplatin

    Combination product

    Oxaliplatin as part of the FLOT regimen 85mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.

  • Docetaxel

    Combination product

    Docetaxel as part of the FLOT regimen 50mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.

  • Pegfilgrastim

    Drug

    Pegfilgrastim or Filgrastim is required on the study and should be administered per the package insert of the commercially obtained drug following each cycle of FLOT for 4 cycles.

  • Filgrastim

    Drug

    Filgrastim or Pegfilgrastim is required on the study and should be administered per the package insert of the commercially obtained drug following each cycle of FLOT for 4 cycles.

  • Surgical Resection of Primary Tumor

    Procedure/Surgery

    Following 4 cycles of preoperative FLOT with RP2 injections, surgical resection of esophageal, GEJ, or gastric primary tumor per standard of care practice.

Treatment groups

34 Participants
are divided into 1 treatment group
Group A: RP2 and FLOTExperimental treatment 8 interventions

Trial outcomes

Primary outcomes

1

Pathologic complete response

Pathologic complete response defined as the absence of residual invasive cancer on histologic examination of the resected esophageal, GEJ, or gastric adenocarcinoma specimen and all sampled regional lymph nodes. This will be assessed in the efficacy population who received at least three intra-tumoral injections of RP2 and underwent subsequent surgical resection.

Time frame
Assessed after completion of neoadjuvant FLOT and intra-tumoral injections of RP2 and surgical resection. This will typically be in the range of 4-5 months from the time of enrollment.

Secondary outcomes

1

Adverse event profile

Frequency of adverse events as categorized and graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 in patients who received at least one dose of study treatment (Safety population).

Time frame
The adverse event reporting period first RP2 intratumoral injection until 30 days post-surgical resection or 56 days after the last administration of RP2 (if no resection or or consent withdrawal).
2

R0 resection rate

R0 resection defined as a complete resection with histologically negative margins with no macroscopic or microscopic residual tumor left behind after resection (Efficacy population).

Time frame
Assessed after completion of neoadjuvant FLOT and intra-tumoral injections of RP2 and surgical resection. This will typically be in the range of 4-5 months from the time of enrollment.
3

Disease-free Survival (DFS)

DFS defined as time from surgical resection of esophageal, GEJ or gastric cancer to death or documented disease recurrence with censoring at the time of last patient contact if lost to follow up, or at the time of data cutoff (Efficacy population).

Time frame
Follow up for this end point may occur for up to 5 years following surgical resection, or data cutoff, whichever comes first.
4

Overall Survival (OS)

OS defined as the time from first study treatment to death with censoring at the time of last patient contact if lost to follow up, or at the time of data cutoff (Safety population).

Time frame
Follow up for this end point may occur for up to 5 years following surgical resection, or data cutoff, whichever comes first.

Other outcomes

1

Exploratory

Blood and tissue samples will be collected, processed, and stored. Endpoints may include pre-/post-treatment change in circulating immune cell subsets, pre-/post-treatment change in tumor infiltrating immune cell subsets, and pre-/post-treatment change in tumor gene expression profiling. These findings will also be evaluated for association with response to therapy.

Time frame
Blood plus/minus tissue samples will be collected during the preoperative FLOT and RP2 injection, at surgical resection, and the first cycle of post-operative FLOT. These collections will occur within the first 6-8 months on the study.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Abramson Cancer Center at Penn Medicine

Lead sponsor

Replimune, Inc.

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: