HTMC0435 and Temozolomide in Treating Patients With Small Cell Lung Cancer

NCT05728619 | Unknown Phase 1

• 1 other identifier: HLND-01-TMZ-Ib/II-01
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 3

Brief Summary

The Phase 1b part of this clinical trial is to investigate the safety and pharmacokinetic (PK) characteristics of HTMC0435 tablets combined with temozolomide in patients with various advanced solid tumors (recurrent small cell lung cancer is preferred). The Phase 2 part of the study is a multi-center, open-label, single-arm trial to investigate the preliminary efficacy of HTMC0435 and temozolomide in patients with recurrent small cell lung cancer (SCLC) at the recommended phase 2 dose.

Conditions

Recurrent Extensive Stage Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicities (DLT) of HTMC0435 combined with Temozolomide

  Cycle 1 Day 1 to Cycle 1 Day 21

• Adverse events (AE) of HTMC0435 combined with Temozolomide

  Through study completion, an average of 6 months

• Maximum tolerable dose (MTD) and RP2D of HTMC0435 combined with Temozolomide

  Through study completion, an average of 6 months

Secondary Outcomes (15)

• Pharmacokinetic measures - the area under the concentration-time curve from dosing (time 0) to time infinity (AUC 0-inf)

  Cycle 1 Day 1 to Cycle 1 Day 9

• Pharmacokinetic measures - the area under the concentration-time curve from dosing (time 0) to time t (AUC 0-t)

  Cycle 1 Day 1 to Cycle 1 Day 9

• Pharmacokinetic measures - apparent clearance rate (CLz/F)

  Cycle 1 Day 1 to Cycle 1 Day 9

• Pharmacokinetic measures - maximum plasma concentrations (Cmax)

  Cycle 1 Day 1 to Cycle 1 Day 9

• Pharmacokinetic measures - time to reach Cmax (Tmax)

  Cycle 1 Day 1 to Cycle 1 Day 9

Other Outcomes (2)

• Changes in neuron-specific enolase (NSE) level from baseline

  Through study completion, an average of 6 months

• Changes in pro-gastrin-releasing peptide (PROGRP) level from baseline

  Through study completion, an average of 6 months

Study Arms (2)

Phase 1b

EXPERIMENTAL

Escalating doses of HTMC0435 and Temozolomide

Drug: HTMC0435; Drug: Temozolomide

Phase 2

EXPERIMENTAL

Recommended phase 2 dose (RP2D) of HTMC0435 and Temozolomide

Drug: HTMC0435; Drug: Temozolomide

Interventions

HTMC0435 DRUG

Oral administration.

Phase 1b; Phase 2

Temozolomide DRUG

Oral administration.

Phase 1b; Phase 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age ≥18 and \<75 years old
• Patients with histologically or cytologically confirmed recurrent or progressive extensive-stage SCLC, who have previously received at least first-line and no more than second-line treatments (HRR mutations are preferred)
• \[Only applicable to phase II part\] At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0\~1
• Expected survival period ≥3 months
• Prior to the enrollment, no serious hematopoietic abnormality, and generally normal function of heart, lung, liver and kidney
• Understand and sign the informed consent form (ICF) voluntarily. Be willing and able to complete routine visits, treatment plans, laboratory examinations and other procedures.

You may not qualify if:

• Prior treatment with any poly (adenosine diphosphate \[ADP\]-ribose) polymerase (PARP) inhibitor
• Prior temozolomide treatment interruption caused by toxicity
• Received treatment with chemotherapy, radiation, biotherapy, endocrine therapy, immunotherapy, or other anti-tumor therapy ≤4 weeks prior to the first dose of HTMC0435
• Any unrecovered AE of prior therapy ≥CTCAE 5.0 Grade 1 (except for toxicity that the investigators judged to have no safety risks, such as alopecia)
• Currently suffering from interstitial lung disease ≥CTCAE Grade 2
• Major surgery (excluding needle biopsy) within 4 weeks before the first dose of HTMC0435
• Past surgical history or severe gastrointestinal diseases that the investigator believes may affect the absorption, distribution or metabolism of the study drug, such as dysphagia, active gastric ulcer, ulcerative colitis, Crohn's disease, ileus, etc.
• History of severe cardiovascular and cerebrovascular diseases
• Received CYP3A4 potent inhibitors or inducers within 7 days before the first dose of HTMC0435 or need to use these medications during the study
• Symptomatic brain metastases or meningeal metastases. Patients with these metastases who have received related treatment need to meet the following conditions before they can be enrolled: no radiographic evidence of progression ≥ 4 weeks after the end of treatment; completion of treatment ≥ 28 days before the first dose; no need for systemic corticosteroids treatment (\>10 mg/day prednisone or equivalent dose) within 14 days before the first dose of HTMC0435
• Active infectious diseases which need systemic anti-infection treatment
• Hepatitis B surface antigen (HBsAg) positive with hepatitis B virus (HBV) -DNA \>1000 copies/mL or \>200 IU/mL; hepatitis C virus antibody (HCV-Ab) positive
• Human immunodeficiency virus antibody (HIV-Ab) positive
• Previous or current diagnosis of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML)
• Women who are pregnant or breastfeeding; women/men who are planning to have a child; women/men who refuse to use medically approved contraceptive measures for contraception during the study treatment and within 6 months after the end of the study

Sponsors & Collaborators

• Shanghai Yidian Pharmaceutical Technology Development Co., Ltd.: lead

Study Sites (3)

Zhejiang Cancer Hospital

Hangzhou, China

RECRUITING

Jiangsu Province Hospital of Chinese Medicine

Nanjing, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, China

RECRUITING

MeSH Terms

Interventions

Temozolomide

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Yun Fan, MD

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Li

CONTACT

+86-21-64311017; clinical_trial@hllife.com.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2023
• First Posted: February 15, 2023
• Study Start: February 3, 2023
• Primary Completion: August 1, 2024
• Study Completion: October 1, 2024
• Last Updated: September 28, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)