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A Study of Catequentinib Hydrochloride (AL3818) in Endometrial, LGSOC, STS or GBM Cancers

ConditionsEndometrial NeoplasmsOvarian NeoplasmsSoft Tissue Sarcoma (STS)Glioblastoma
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAdvenchen Pharmaceuticals, LLC.

About this trial

This phase 1b/2a study evaluates the investigational oral drug catequentinib hydrochloride (AL3818), given alone or with AL58805, temozolomide, or lomustine (CCNU), in adults with advanced or metastatic solid tumors. The phase 1b part will identify doses that can be given safely based on side effects during the first treatment cycle. The phase 2a part will estimate whether the treatments shrink non-brain tumors or keep glioblastoma from worsening for at least 6 months.

The study is open label, which means participants and study investigators will know which treatment is given. Tumor response will be assessed with RECIST version 1.1. The study will also evaluate how the investigational drugs move through the body, the duration of tumor response, progression-free survival, overall survival, and treatment safety.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥ 18 years.

Pathologically confirmed recurrent or metastatic solid tumors such as NSCLC, SCLC, STS, Thyroid, Endometrial, LGSOC, GBM and breast cancer (Phase 2a: STS, Endometrial, LGSOC and GBM ); GBM can only have histological confirmation of diagnosis;

Failure of at least 1 prior line of standard therapy (disease progression after treatment or intolerable treatment toxicities); concurrent chemoradiation therapy and adjuvant chemotherapy such as containing temozolomide will be considered as 1 line of prior therapy

no standard or effective treatment available.

Disqualifiers

Treatment with an investigational agent within 28 days of enrollment.

Cytotoxic chemotherapy, targeted therapies, immunotherapy, or radiotherapy within 28 days (42 days in cases of mitomycin C, nitrosourea, lomustine) prior to enrollment. Prior bevacizumab or other antiangiogenic therapies for phase 2 part of the GBM cohort (however, use of bevacizumab for radiation necrosis or toxicity is allowed unless it is within 28 days prior to enrollment).

Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19 within 14 days prior to enrollment and during the study unless there is an emergent or life- threatening medical condition that required it.

Known allergy or intolerance to investigational drugs (e.g., AL3818, AL58805, temozolomide, CCNU, etc.) and excipients. (For example, patients who have had severe allergic reactions such as rash or anaphylactic shock after previous use of temozolomide.)

Trial design

Design model

Parallel

Treatments tested in this trial

  • AL58805

    Drug

    AL58805 is a novel chemical-structure antitumor drug with independent intellectual property rights. It functions as a novel dual-target PI3K/mTOR kinase inhibitor, exhibiting effects such as inhibiting tumor cell growth and proliferation, suppressing tumor nutrient metabolism, and exerting anti-angiogenic activity. By simultaneously inhibiting both PI3K and mTOR, it completely blocks the entire PI3K/AKT/mTOR signaling pathway at relatively low safe doses, thereby enhancing antitumor efficacy.

  • AL3818

    Drug

    AL3818 is a novel small molecule dual receptor tyrosine kinase inhibitor, which shows highly selective inhibition of fibroblast growth factor receptor (FGFr) and vascular endothelial growth factor receptor (VEGFR). Preclinical studies of this agent in mouse models, including various cancer xenografts, have demonstrated that treatment of tumor-bearing mice with AL3818 induces tumor reductions.

  • Temozolomide (TMZ)

    Drug

    Temozolomide is an alkylating agent, which metabolizes to generate active substance methyl triazene imidazole formamide (MTIC), which interferes with the replication and repair of tumor cell DNA and induces apoptosis of cancer cells.

  • CCNU

    Drug

    CCNU is an alkylating agent that works by damaging cancer cell DNA, ultimately leading to cell death. It is lipid-soluble, allowing it to cross the blood-brain barrier, which is crucial for treating brain tumors.

Treatment groups

138 Participants
are divided into 7 treatment groups

7

Treatment groups

See each treatment group below.

Group A: P1b.1-A1: Cohort A1 (Monotherapy RP2D determination, Solid Tumors)Experimental treatment 1 intervention
Group B: P1b.1-A2: Cohort A2 (Combination therapy RP2D determination, Endometrial, LGSOC or STS)Experimental treatment 2 interventions
Group C: P1b.2-B1: Cohort B1 (Monotherapy RP2D determination, Glioblastoma)Experimental treatment 1 intervention
Group D: P1b.2-B2: Cohort B2 (Combination therapy RP2D-B determination, Glioblastoma)Experimental treatment 3 interventions
Group E: P2a.3-C: Cohort C (AL3818 monotherapy, Endometrial, LGSOC cancer)Experimental treatment 1 intervention
Group F: P2a.3-D: Cohort D (AL58805 + AL3818, Endometrial, LGSOC and STS)Experimental treatment 2 interventions
Group G: P2a.3-E: Cohort E (AL3818 + temozolomide or CCNU, Glioblastoma)Experimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Recommended combination dose (RCD)

Determine the recommended combination dose (RCD) of AL3818 in combination with other anti-tumor agents based on evaluation of dose-limiting toxicity (DLT) events during Phase 1b.

Time frame
36 months
2

Objective Tumor Response Rate (ORR)

Evaluate the proportion of participants who achieve Complete Response (CR) or Partial Response (PR) as the best overall tumor response according to RECIST version 1.1; tumor response in participants with GBM is assessed according to RANO 2.0.

Time frame
36 months

Secondary outcomes

1

Pharmacokinetic endpoint: Time to Maximum Plasma Concentration (Tmax)

Time from study drug administration to the observed maximum plasma concentration (Tmax) of AL3818 and, where applicable, AL58805, determined from protocol-specified pharmacokinetic sampling.

Time frame
36 months
2

Pharmacokinetic endpoint: Peak Plasma Concentration (Cmax)

Evaluate the maximum observed plasma concentration (Cmax) of AL3818 and, where applicable, AL58805 based on plasma concentration-time data collected at protocol-specified pharmacokinetic sampling time points.

Time frame
36 months
3

Pharmacokinetic endpoint: Area Under the Curve (AUC)

Evaluate the area under the plasma concentration-time curve (AUC) of AL3818 and, where applicable, AL58805 based on plasma concentration-time data collected at protocol-specified pharmacokinetic sampling time points.

Time frame
36 months
4

Duration of Response (DOR)

Evaluate the time from the date of first documented objective response, defined as Complete Response (CR) or Partial Response (PR), to the date of documented disease progression or death from any cause, whichever occurs first, according to RECIST version 1.1 or RANO 2.0 for GBM.

Time frame
36 months

Other outcomes

Sponsors and contacts

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

Advenchen Pharmaceuticals, LLC.

Lead sponsor

Source ClinicalTrials.gov

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