DS-3201b and Irinotecan for Patients With Recurrent Small Cell Lung Cancer

NCT03879798 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 18-553
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 7

Brief Summary

This study will test the safety of the study drug, DS-3201b, given in combination with irinotecan to people who have recurrent small cell lung cancer (SCLC).

Conditions

Small Cell Lung Cancer

Keywords

DS-3201b; Irinotecan; 18-553

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) (Phase l) of DS-3201/Valemetostat

  Will employ a standard 3-by-3 dose-escalation phase I study design to investigate the maximum tolerated dose (MTD) of DS-3201b/valemetostat in combination with fixed dose irinotecan. The study population for Phase I dose-escalation will include only patients who complete at least 1 full cycle of treatment (including the initial 7-day safety run-in and the complete 21-days of Cycle 1); only these patients will be considered evaluable for DLT and determination of the MTD.

  1 year

• Objective Response Rate (ORR) (Phase II)

  The Response Evaluation Criteria in Solid Tumors Group (RECIST v1.1) criteria will be used to evaluate the response to treatment

  1 year

Study Arms (1)

DS-3201b and Irinotecan

EXPERIMENTAL

The first part of this study is a phase I trial to assess the safety and tolerability of DS-3201b in combination with fixed-dose irinotecan. The second part of this study will be an open label, single-arm phase II study of DS-3201b at the established recommended phase II dose (RP2D) in combination with fixed-dose irinotecan.

Drug: DS-3201b; Drug: irinotecan

Interventions

DS-3201b DRUG

100 mg daily

DS-3201b and Irinotecan

irinotecan DRUG

Irinotecan 125 mg/m\^2 intravenously on days 1 and 8 every 3 weeks in a 21-day cycle.

DS-3201b and Irinotecan

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form (ICF)
• Ability to comply with the study protocol as per the investigator's judgment
• Age ≥ 18 years at the time of signing the ICF
• Life expectancy ≥ 12 weeks
• Karnofsky performance status ≥ 70% or ECOG 0, -1 or 2
• Radiographically documented progression of disease after prior treatment with a platinum doublet regimen. Patients who received a platinum doublet regimen in combination with immunotherapy are still eligible for the study.
• Measurable disease according to RECIST v1.1
• Adequate tissue sample available for both IHC testing of IHC testing of SLFN11 and H3K27me3 and molecular profiling (archived tissue block or 20 unstained slides). Tissue sample can be either from an initial pre-platinum-based chemotherapy sample OR from a repeat biopsy sample after progression on platinum-based chemotherapy.
• Concurrent consent to the appropriate biospecimen research protocols at MSKCC (#06-107 Storage and Research Use of Human Biospecimens) and at JHU.
• Adequate hematologic and end-organ function, as defined by the following laboratory test results obtained within 14 days prior to initiation of study treatment:
• °Adequate bone marrow function as defined by:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (1500/µL) without granulocyte colony-stimulating factor support within 2 weeks prior to starting study therapy
• Hemoglobin ≥ 9 g/dL (transfusions to meet this criterion are allowed)
• Platelets ≥ 150 x 10\^9/L without transfusion
• Adequate renal function as defined by:

You may not qualify if:

• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of study procedures.
• Untreated CNS metastases
• Patients with treated CNS metastases are allowed on the study as long as their clinical symptoms are adequately controlled and the daily dose of steroid use is equivalent to or less than 10 mg of prednisone.
• Is receiving concomitant treatment with a strong inhibitor or inducer of CYP3A4/5 within 7 days of first receipt of DS-3201b.
• °Consumption of herbs/fruits that may have an influence on PK of DS-3201b (strong CYP3A inhibitors or inducers) such as St. John's wort, star fruit, Seville orange or Seville orange-containing foods and beverages, grapefruit or grapefruit-containing food or beverages should be avoided from 14 days prior to the start of the study and throughout the entire study.
• Prior exposure to DS-3201b or other inhibitors of enhancer of zeste homologue-2 (EZH2)
• Prior exposure to topoisomerase inhibitors, including topotecan and irinotecan
• Refractory nausea and vomiting, malabsorption, biliary shunt, significant bowel resection, or any other condition that significantly affects gut motility or absorption and would preclude adequate absorption of DS-3201b in the opinion of the treating physician and/or PI.
• Currently receiving anticancer therapies or who have received anticancer therapies within 2 weeks prior to the initiation of study treatment. Anticancer therapies include chemotherapy, biologics, targeted therapies, immunologics, or other investigational therapy.
• Currently receiving radiation therapy, or who have received radiation within 2 weeks prior to the initiation of study treatment.
• Patients who have not recovered to Grade ≤1 or baseline from adverse events due to prior anticancer therapy.
• Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia).
• NOTE: Procedures such as a percutaneous biopsy, pleural catheter insertion, placement of a central venous catheter or other minor procedures are permitted.
• Uncontrolled or significant cardiovascular disease, including the following:
• Evidence of prolongation of QT/QTc interval (e.g., repeated episodes of QT corrected for heart rate using Fridericia's method \[QTcF\] \>450 ms for men and \>470 ms for females) ECG from 12-lead electrocardiogram for measurement of corrected QT interval according to the Fridericia formula: electrocardiogram must be registered at rest. For any EKG assessment, if the initial EKG shows a prolonged QTc, then two additional EKGs will be obtained, resulting in three specimens taken after a space of

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Irinotecan

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Charles Rudin
• Organization: Memorial Sloan Kettering Cancer Center

rudinc@mskcc.org

646-888-4527

Study Officials

• Charles Rudin, MD, PhD

  Memorial Sloan Kettering Cancer 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: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a non-randomized phase I/II trial assessing the safety and tolerability of DS-3201b in combination with irinotecan in patients with recurrent small cell lung cancer.

Study Record Dates

• First Submitted: March 15, 2019
• First Posted: March 19, 2019
• Study Start: March 15, 2019
• Primary Completion: May 2, 2023
• Study Completion: May 2, 2023
• Last Updated: October 10, 2024
• Results First Posted: October 10, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF

Locations

US (7)