Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Rare Diseases

Prostatic Neoplasms

Breast Neoplasms

Pancreatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Disease Progression

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Poly(ADP-ribose) Polymerase Inhibitors

Tubulin Modulators

Single Arm Study, all participants will receive AMXI-5001.

Phase I will enroll up to 70 participants to identify the Recommended Phase II daily dose in the treatment of various cancers and to characterize the safety, pharmacology, and clinical efficacy of AMXI-5001. AMXI-5001 is administered orally twice daily, with food. AMXI-5001 is administered weekly on a continuous 7-day schedule. Each cycle is 28 days.

AMXI-5001:Dose Escalation Phase I

Phase II will enroll up to 52 study participants to further characterize the safety, pharmacology, and clinical efficacy of AMXI-5001. AMXI-5001 is administered orally twice daily, with food. AMXI-5001 is administered weekly on a continuous 7-day schedule. Each cycle is 28 days.

AMXI-5001:Dose Expansion Phase II

Pamela Munster, MD

ATLAS-101 is a Phase I/II clinical trial of AMXI-5001 in adult participants with advanced malignancies who have previously failed other therapies. The study has two phases. The purpose of Phase I (Dose Escalation) is to confirm the appropriate treatment dose and Phase II (Dose Expansion) is to characterize the safety and efficacy of AMXI-5001.

AMXI-5001 is an orally available dual PARP (poly adenosine diphosphate \[ADP\] ribose polymerase) and microtubule polymerization inhibitor. ATLAS-101 is a Phase I/II, open label, multi-center, non-randomized Dose Escalation and Dose Expansion study in participants with advanced malignancies. Study enrollment is approximately 122 participants. All participants receive oral AMXI-5001, twice daily, as monotherapy. Following Phase I (Dose Escalation) to identify the Maximum Tolerated Dose and the Recommended Dose for use in Phase II, additional participants will be enrolled into the Dose Expansion Phase to further characterize the safety, pharmacology, and clinical efficacy of AMXI-5001.

A Trial of AMXI-5001 for Treatment in Patients With Advanced Malignancies

A Phase I/II, Open Label, Multi-center, Non-randomized Dose Escalation and Dose Expansion Study of AMXI-5001 in Patients With Advanced Malignancies

The highest dose is defined at which no more than 1 of 6 evaluable participants has had a Dose Limiting Toxicity (DLT) according to NCI CTCAE V5.0 criteria and determination by Investigator and Data and Safety Monitoring Committee.

The RP2D is based upon the review of all available data including safety, pharmacokinetic, preliminary anti-tumor activity, and MTD.

Concentrations of AMXI-5001 in plasma samples at different time points are measured. Standard pharmacokinetic parameters are calculated.

The safety profile of AMXI-5001 is defined by the incidence of treatment emergent adverse events, laboratory abnormalities, and ECG measurements.

Overall Survival (OS), Objective Response Rate (ORR), Duration of Response (DOR), and Progression-free Survival (PFS) are assessed by RECIST V1.1 criteria.

AtlasMedx, Incorporated

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

Starting dose of TPI 287 90 mg/m\^2 IV on Days 1, 8, 15 + Temozolomide (Temodar) PO at 85 mg/m\^2 on Days 1-5.

Starting dose cycle 1, 90 mg/m2 by vein (IV) on Days 1, 8, 15 (+/- 1 day)

TPI 287

Starting dose cycle 1, 85 mg/m\^2 by mouth (PO) daily, Day 1 to 5.

Temodar (Temozolomide)

Rodabe N Amaria, MD

The goal of the Phase I portion of this study is to find the highest tolerable dose of TPI 287 that can be given in combination with Temodar (temozolomide) to patients with metastatic melanoma.

The goal of the Phase II portion of this study is to learn if TPI 287, given in combination with temozolomide, can control metastatic melanoma. The safety of this combination will also be studied. NOTE: Study stopped before progressing to Phase II portion.

Study Drugs:

TPI 287 is designed to block tumors from growing by preventing cancer cells from dividing.

Temozolomide is designed to kill cancer cells by causing breaks in the DNA (genetic material) of the cell.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. Up to 8 groups of 6 participants will be enrolled in the Phase I portion of the study, and up to 64 participants will be enrolled in Phase II.

If you are enrolled in the Phase I portion, the dose of TPI 287 and temozolomide you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of TPI 287 and temozolomide. Each new group will receive a higher dose of TPI 287 and temozolomide than the group before it, if no intolerable side effects were seen. If any of these participants have a dose limiting toxicity, 6 additional participants will be added at the same dose. If a dose limiting toxicity occurs again, the dose level below this will be considered the maximum tolerated dose.

If any participant experiences a life threatening side effect, no additional participants will be enrolled into that dose level and no higher doses will be given. An additional 3 participants will be treated at the dose level below the one with life threatening toxicity. Once the maximum tolerated dose of the combination is found, Phase II of the study will open.

If you are enrolled in the Phase II portion, you will receive the drug combination at the highest dose that was tolerated in the Phase I portion

Central Venous Catheter (CVC):

You will have a CVC placed. A CVC is a sterile, flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure.

Study Drug Administration:

You will receive TPI 287 by vein over 1 hour (+/- 10 minutes) on Days 1, 8, and 15 (+/- 1 day) of each 28 day study cycle. Before you receive each dose of TPI 287, you will receive dexamethasone, Benadryl (diphenhydramine), and Pepcid (famotidine) by vein to help prevent allergic reaction. You will also receive drugs to prevent nausea and vomiting. Your vital signs will be measured before and 30 minutes following the end of the infusion of TPI 287. Your vitals will be measured more often, if needed.

You will take temozolomide tablets by mouth on Days 1-5 at bedtime. You should not eat for at least 1 hour before and 1 hour after taking temozolomide.

Study Visits:

Before each cycle, your performance status will be recorded and you will have a physical exam. You will also be asked about any symptoms you may be experiencing and any drugs you are taking.

On Days 1, 8, and 14 of each cycle:

-Blood (about 1 teaspoon) will be drawn for routine tests before you receive TPI 287.

On Day 22 of each cycle:

-Blood (about 1 teaspoon) will be drawn for routine tests.

Every 8 weeks, you will have a CT scan or MRI scan to check the status of the disease. If you have brain metastasis, you will have an MRI of the brain every 4 weeks. If you do not have brain metastasis, you will have MRI of the brain every 8 weeks.

Length of Study:

You will continue taking the study drugs for as long as you are benefitting. You will be taken off study if the disease gets worse or intolerable side effects occur.

End-of-Treatment Visit:

About 4 weeks after you stop taking TPI 287 in combination with Temozolomide, you have an end-of-study visit. At this visit, the following tests and procedures will be performed:

* You will have a physical exam.
* You will be asked about any complications or side effects you may be experiencing.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* If your doctor thinks it is needed, you will have a CT scan or MRI scan to check the status of the disease.

This is an investigational study. TPI 287 is not FDA approved or commercially available. At this time, TPI 287 is being used in research only. Temozolomide is FDA approved and commercially available for primary brain cancer. The use of temozolomide in combination with TPI 287 is investigational.

Up to 106 patients will take part in this study. All patients will be enrolled at MD Anderson.

A Phase I Study of TPI 287 - Temozolomide Combination in Melanoma

A Phase I/II Open-Label Study TPI 287 in Combination With Temozolomide in Patients With Metastatic Melanoma

MTD is highest dose level in which 6 patients treated with at most 1 experiencing dose limiting toxicity (DLT).

Maximum Tolerated Dose (MTD), measured by clinical and laboratory adverse events.

Response rate provided along with a 95% credible interval. Logistic regression models used to assess the association between progression-free survival at 6 months and covariates of interest. Additionally, Cox proportional hazards regression models will be fit to model the association between progression-free survival and the same covariates. Simon's minimax two-stage design used to evaluate the response rate.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Trial of AMXI-5001 for Treatment in Patients With Advanced Malignancies	NCT04503265	Advanced Malign... Breast Cancer Ovarian Cancer Homologous Reco... Prostate Cancer Pancreatic Canc...	AMXI-5001:Dose ... AMXI-5001:Dose ...	18 Years -	AtlasMedx, Incorporated
A Phase I Study of TPI 287 - Temozolomide Combination in Melanoma	NCT01067066	Melanoma	TPI 287 Temodar (Temozo...	15 Years -	M.D. Anderson Cancer Center
A Phase I Study of TPI 287 - Temozolomide Combination in Melanoma	NCT01067066	Melanoma	TPI 287 Temodar (Temozo...	15 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for microtubule inhibitor