Phase I study with increasing dosage and treatment duration

AXL1717

Michael Bergqvist, MD

A dose escalating phase Ia-b clinical trial of the IGF-1 receptor inhibitor AXL1717 in patients with advanced cancer.

The objective is to study the safety and pharmacokinetics of AXL1717 and to define an appropriate Phase 2 dose for further studies. This is the first study in man. The study is not designed to show tumor response.

A Dose Escalating Clinical Trial of the IGF-1 Receptor Inhibitor AXL1717 in Patients With Advanced Cancer

A Dose Escalating Phase Ia-b Clinical Trial of the IGF-1 Receptor Inhibitor AXL1717 in Patients With Advanced Cancer: A Prospective, Single Armed, Open Label, Dose-finding Phase Ia-b Study

Axelar AB

Michael Bergqvist

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Carboplatin

AXL1717 in combination with Gemcitabine HCL and Carboplatin

A repeated BID treatment for 14 days, followed by a 7 day observation period for two treatment periods

Michael Bergqvist, M.D., Ph.D

This is a open single-center, explorative, Phase I pilot dose finding study including patients treated with AXL1717 in addition to standard chemotherapy of gemcitabine HCL and carboplatin.

Open single-center, explorative, Phase I pilot study including patients treated with AXL1717 in addition to standard chemotherapy of gemcitabine HCL and carboplatin. Patients will be treated within the study for 2 treatment cycles of 3 weeks each. Survival data will be obtained. Tumor assessment will be conducted at baseline and then at the end of the study period. Concomitant supportive therapies will be allowed.

A Study of the IGF-1R Inhibitor AXL1717 in Combination With Gemcitabine HCL and Carboplatin to Treat Non-small-cell Lung Cancer (NSCLC)

A Phase I Pilot Study of the IGF-1R Inhibitor AXL1717 in Combination With Gemcitabine HCL and Carboplatin in Previously Untreated, Locally Advanced, or Metastatic Squamous Non-small-cell Lung Cancer

A dose finding pilot study to evaluate safety and pharmacokinetics in combination with Gemcitabine HCL and Carboplatin during two treatment cycles, i.e. 6 weeks.

Rare Diseases

Adenocarcinoma

Carcinoma, Squamous Cell

Adenocarcinoma of Lung

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Lung Adenocarcinoma

Docetaxel

Tubulin Modulators

Antimitotic Agents

AXL1717 administered as oral suspension at 400 mg twice daily for 21 days per cycle; i.e. daily for up to four cycles

Docetaxel administered as a standard treatment (75 mg/m2 IV infusion over 1 hour) once every three weeks throughout the 4-cycle study

Michael Bergqvist, MD, PhD

The purpose of this study is to compare effectiveness and safety of experimental anticancer medicine, AXL1717, and docetaxel in patients with squamous cell carcinoma or adenocarcinoma of the lung.

Non-Small-Cell lung Cancer (NSCLC) is the most common form of lung cancer, and treatment with cytotoxic chemotherapy only provides a 10% reduction in the risk of death in patients with advanced NSCLC. One-third of all non-resectable advanced NSCLC patients in second line do not receive chemotherapy treatment at all. In the absence of treatment the Progression-Free Survival (PFS) for NSCLC patients is dismal, in the range of 6-8 weeks, and treatment only modestly improves the median PFS to 10-11 weeks. Therefore, because of an overall poorer prognosis for patients with advanced NSCLC, development of new agents is urgently needed.

AXL1717 is a small molecule experimental product developed by Axelar AB as anticancer agent for oral administration. AXL1717 inhibits the insulin-like growth factor 1 (IGF-1), which is often over expressed in lung tumors and can mediate the proliferation of lung cancer cells and resistance to therapy. Results of previous preclinical and clinical studies indicate that AXL1717 will be tolerable and effective in patients with previously-treated, advanced squamous cell carcinoma (SCC) and adenocarcinoma (AC) histological subtypes of NSCLC.

This is an open label, randomized, multi-center, Phase II study to investigate AXL1717 compared to docetaxel in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the lung. Patients with previously treated, locally advanced or metastatic SCC or AC subtypes of NSCLC in need of additional treatment will be enrolled in the study. Patients will be randomized to either AXL1717 or to docetaxel group as monotherapy, in a 3:2 ratio for each NSCLC subtype. Patients in AXL1717 group will receive 400 mg AXL1717 twice daily (BID) as oral suspension for 21 days per cycle; i.e. daily for up to four cycles unless a dose interruption, delay, or reduction is required. Docetaxel will be administered as a standard treatment (75 mg/m2 IV infusion over 1 hour) once every three weeks throughout the 4-cycle study. The primary objective of the study is to compare the rate of progression-free survival (PFS) at 12 weeks between patients treated with AXL1717 and patients treated with docetaxel. Additional efficacy and safety parameters will be monitored throughout the study. Patients treated with AXL1717 who are responding to treatment or remain stable at the end of 4 cycles may be offered an extension of treatment with AXL1717.

Study of AXL1717 Compared to Docetaxel to Treat Squamous Cell Carcinoma or Adenocarcinoma of the Lung

Phase II, Randomized, Open-label Study of the IGF-1R Inhibitor AXL1717 Compared to Docetaxel in Patients With Previously Treated, Locally Advanced, or Metastatic Squamous Cell Carcinoma or Adenocarcinoma of the Lung

Symptoms and General Pathology

Recurrence

Glioblastoma

Astrocytoma

Oligodendroglioma

Ependymoma

Gliosarcoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Oligoastrocytoma

Anaplastic Oligoastrocytoma

Anaplastic Ependymoma

Neuroepithelioma

In the first phase, 10-20 patients will be enrolled and treated with 300mg (original range of starting dose was 300-520mg) BID of AXL1717 for 28 days. The primary endpoint of the first phase is to determine the recommended Phase 2 dose (RP2D) of AXL1717 and to assess the safety and toxicity of AXL1717. The study has a 3+3 design and the first cohort will be treated with 300 mg AXL1717 BID for 28 days repeated in up to 5 cycles. The highest dose level without DLT or with maximally one DLT out of 6 patients will be the RP2D. Non-progressing patients may be treated for a total of five 28-day cycles (24 weeks).

Robert Aiken, MD

This is a single-center, open-label, non-randomized, Phase I/IIa study to investigate the safety, tolerability, and antitumor efficacy of AXL1717 (picropodophyllin as active agent formulated in an oral suspension; PPP) in patients with recurrent malignant astrocytomas (glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, and anaplastic ependymoma). Patients will be treated for up to 5 cycles. A treatment cycle is defined as 28 days+7 days rest (28+7 days during cycle 1 to 4, and 28 days during cycle 5). The following cycle will not be started until the treatment continuation criteria are fulfilled. Concomitant supportive therapies will be allowed.

AXL1717, as a ready-to-use suspension of picropodophyllin for oral administration, will be distributed in bottles for single use at a concentration of 25 mg/mL. Fixed doses will be used, i.e. there are no adjustments for weight or body surface. There will be no randomization or blinding in the study.

The trial will be divided in two phases. In the first phase, 10-20 patients will be enrolled and treated with 300-520 mg BID of AXL1717 for 28 days. The primary endpoint of the first phase is to determine the recommended Phase 2 dose (RP2D) of AXL1717 in patients with recurrent or progressive glioblastoma and to assess the safety and toxicity of AXL1717 in this patient population. The study has a 3+3 design and the first cohort will be treated with 400 mg AXL1717 BID for 28 days repeated in up to 5 cycles. If dose-limiting toxicity (DLT) such as neutropenia occurs, dosing will be interrupted and the individual patient will, following normalization, be restarted on the same or a lower dose level according to standardized procedure. If two or three of the first 3 patients on a specific dose level experience a DLT during the first 28 days of treatment with AXL1717, the following patients will be treated with a lower dose level. If one DLT occurs during the first 28 days of dosing in the first 3 three patients another 3 patients will be treated with the same dose level. If 2 of the 6 patients display DLT, the next patients will be treated with a lower dose level. The highest dose level without DLT or with maximally one DLT out of 6 patients will be the RPTD. All assessments with respect to dose adjustments for subsequent cohorts will be done during the first 28 days of treatment. Non-progressing patients may be treated for a total of five 28-day cycles (24 weeks).

In the second phase, 12 patients will be enrolled and treated with the identified RP2D of AXL1717 for 28 days repeated in five cycles. The primary endpoints of phase II is to assess the proportion of patients who are progression-free at 24 weeks and to assess safety, tolerability, and adverse event profile of AXL1717.

Phase I/II Trial of AXL1717 in the Treatment of Recurrent Malignant Astrocytomas

Phase I/II Clinical Trial of the Safety, Tolerability, and Anti-tumor Efficacy of the IGF-1R Inhibitor, AXL1717 (Picropodophyllin), in the Treatment of Recurrent Malignant Astrocytomas

To assess the ability of AXL1717 to inhibit tumor proliferation as assessed by blood IGFBP-1 through IGFBP-7, growth hormone (GH) levels, C-peptide, IGF-1 (free and total), and IGF-2 levels, insulin, and analysis of tumor tissue of patients treated with AXL1717 for 5 days before surgical re-operation by examining for the IGF-1R signal transduction pathway in the resected brain tumor tissue, and correlate with outcome.

To determine the recommended phase II dose (RPTD) of AXL1717 in recurrent malignant astrocytomas defined as the highest dose level without DLT (Dose Limiting Toxicity) or with maximally one DLT out of 6 patients will be the RPTD.

To determine if AXL1717 has any antitumor effect as a single agent treatment in recurrent malignant astrocytomas by evaluating PFS at 24 weeks

To identify the Maximum Tolerated Dose (MTD) of AXL1717 in the Phase I subject population. MTD is the highest dose of AXL1717 with the lowest average per subject cases of DLT.

To assess potential molecular markers that might predict optimum response sub-population groups

To evaluate surrogate molecular markers of IGF-1R pathway activation/inhibition after treatment with AXL1717 in patients with malignant astrocytomas

To determine time-to-progression (TTP) and overall survival (OS) of patients treated with AXL1717. Only overall survival for subjects is prolonged stable disease was analyzed.

To assess overall response rate (ORR) in recurrent malignant astrocytomas after treatment with AXL1717

To identify surrogate imaging evidence of response on MRI sequences (especially T2- FLAIR, DWI, Perfusion MRI and multi-voxel MRS).

Rush University Medical Center

400mg BID

300mg BID

215mg BID

Subjects who started and completed the study on 400mg BID

AXL1717, 400mg Initial Dose

Subjects who started the study on 300mg BID. one subject was escalated to 400mg BID and 2 subjects were de-escalated to 215mg BID

AXL1717, 300mg Initial Dose

Total

Age, Continuous

Sex: Female, Male

Crista Brawley

All study participants who received different doses of the same formulation of AXL1717.

All Study Participants

Phase I - Determine Recommended Phase II Dose

This group was never established as Phase I of the study was never completed and thus Phase II was never initiated.

Phase II Subject Group

Phase II of this study was never initiated and so no data was collected or analyzed for this endpoint.

Phase II - To Determine if AXL1717 Has Any Antitumor Effect

Phase I - To Identify the Maximum Tolerable Dose

All subject who participated in the study and received at least one cycle of treatment.

the data for this outcome measure was not collected and/or analyzed. There is no data to report.

Phase I - Molecular Markers of Optimum Response

first 2 subjects were started on 400mg BID initial dose.

AXL1717, 400mg Initial Does

AXL1717, 300mg Initial Does

None of the secondary outcome measures were collected or analyzed as this study was conducted using the oral suspension of AXL1717 and there is a new formulation of AXL1717 in development (capsule). Decision was made to abandon other analysis or data collections in regards to secondary outcomes.

Phase I - Molecular Markers of IGF (Insulin Like Growth Factor)-1R Pathway

Phase II Study Population

Phase II - Time-To-Progression (TTP) and Overall Survival (OS)

Phase II of the study was never initiated. No data was gathered or analyzed.

Phase II - Overall Response Rate

Phase II of the study was never initiated.

Phase II - Identify Evidence of Response on Imaging

Phase II portion of this study was not initiated as the phase 1 piece was not completed fully. This endpoint was not explored and data was not collected or analyzed

Exploratory Endpoint - Determine Antitumor Effect

Number of Participants with Imaging Evidence of Response on MRI (magnetic resonance imaging)sequences by RANO criteria (with additional special attention to T2-FLAIR, DWI (diffusion-weighted imaging), perfusion MRI and multi-voxel MRS (magnetic resonance spectroscopy) sequences).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Dose Escalating Clinical Trial of the IGF-1 Receptor Inhibitor AXL1717 in Patients With Advanced Cancer	NCT01062620	Solid Tumors	AXL1717	18 Years -	Axelar AB
A Study of the IGF-1R Inhibitor AXL1717 in Combination With Gemcitabine HCL and Carboplatin to Treat Non-small-cell Lung Cancer (NSCLC)	NCT01466647	Non Small Cell ...	AXL1717	18 Years -	Axelar AB
Study of AXL1717 Compared to Docetaxel to Treat Squamous Cell Carcinoma or Adenocarcinoma of the Lung	NCT01561456	Non-small-cell ... Squamous Cell C... Adenocarcinoma ...	AXL1717 Docetaxel	18 Years -	Axelar AB
A Study of the IGF-1R Inhibitor AXL1717 in Combination With Gemcitabine HCL and Carboplatin to Treat Non-small-cell Lung Cancer (NSCLC)	NCT01466647	Non Small Cell ...	AXL1717	18 Years -	Axelar AB
Phase I/II Trial of AXL1717 in the Treatment of Recurrent Malignant Astrocytomas	NCT01721577	Glioblastoma Gliosarcoma Anaplastic Astr... Anaplastic Olig... Anaplastic Olig... Anaplastic Epen...	AXL1717	18 Years -	Rush University Medical Center

Spots Global Cancer Trial Database for axl1717

Every month we try and update this database with for axl1717 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for axl1717

Every month we try and update this database with for axl1717 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for axl1717 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.