Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Breast Neoplasms

Triple Negative Breast Neoplasms

Pancreatic Neoplasms

Carcinoma, Hepatocellular

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Cholangiocarcinoma

Melanoma

Sarcoma

Skin Neoplasms

Sarcoma, Synovial

Colonic Neoplasms

Breast Diseases

Skin Diseases

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

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms, Connective and Soft Tissue

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Neoplasms, Connective Tissue

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Bile Duct Cancer

Soft Tissue Sarcoma

Synovial Sarcoma

Neuroendocrine Tumor

Neuroepithelioma

Herbal and Botanical

All Drugs and Chemicals

Cola

The dose cohorts will be 0.5, 1, 2, 4, and 8 mg/kg IV once weekly (QW)

Triple Negative Breast Cancer Expansion phase n=30

ST316

Steve Kaesshaefer

Xiomara Menendez, RN

Anthoney El-Khoueiry, MD

Josh Henninger, MD

Jason Henry, MD

Julie Burns, BSN

Nehal Lakhani, MD

JoAnna Gontarz, MSN

Niharika Mettu, MD PhD

Staci Vogel

Steven Powell, MD

Abi Vainstein-Haras

This is an open-label, two-part, phase 1-2 study designed to determine the safety, tolerability, PK, pharmacodynamics (PD), and proof-of-concept efficacy of ST316 administered IV in subjects with selected advanced solid tumors likely to harbor abnormalities of the WNT/β-catenin signaling pathway. The study consists of two phases: a phase 1 dose escalation/regimen exploration phase and a phase 2 expansion phase.

A Phase 1-2 of ST316 With Selected Advanced Unresectable and Metastatic Solid Tumors

A Phase 1-2 Dose-escalation and Expansion Study of ST316 in Subjects With Selected Advanced Unresectable and Metastatic Solid Tumors

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

Area under the concentration-time curve over the dosing interval

DOR is defined for participants achieving a confirmed CR+PR as the time from the initial response of CR+PR per investigator review according to RECIST 1.1 criteria to disease progression or death of any cause, whichever occurs earlier

Area under the concentration-time curve over the dosing interval time from time 0 extrapolated to infinite time

The time take to reach Maximum observed serum concentration

Overall survival (OS) is defined as time from first study treatment to death due to any cause.

Progression-free survival (PFS) is defined as time from first study treatment to a documented disease progression according to RECIST version 1.1, as determined by the investigator, or death due to any cause, whichever occurs earlier.

ORR defined as percentage of participants with confirmed best overall response of Confirmed complete response (CR) and partial response (PR) per investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Sapience Therapeutics

Infections

Carcinoma, Merkel Cell

Communicable Diseases

Polyomavirus Infections

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Carcinoma, Neuroendocrine

Merkel Cell Carcinoma

Pasireotide

Somatostatin

Hormones

Hormone Antagonists

Pasireotide, will be administered to all patients by s.c. injection, beginning with a dose of 300 μg administered three times daily (t.i.d.) for 2 weeks. If no pasireotide-related clinically meaningful/uncontrolled grade 3 or grade 4 adverse events occur the dose will be administered to all patients at an increased dose of 600 μg t.i.d. for 2 weeks, followed by 2 weeks of 900 μg t.i.d. and followed by 2 weeks of 1200 μg t.i.d. After the 8 weeks period, patients will be kept on treatment drug (highest dose without clinically meaningful/uncontrolled AEs), switched to the corresponding pasireotide LAR dose and followed up for an extra 6 months.

At the start of the follow-up phase patients will be switched to pasireotide LAR administered intramuscularly every 28 days by using the following conversion algorithm so that the steady state PK exposure (Cmax and Ctrough) of pasireotide will be maintained: 300 μg s.c. t.i.d. fi 20mg LAR i.m. q 28 days 600 μg s.c. t.i.d. fi 40 mg LAR i.m. q 28 days 900 μg s.c. t.i.d. fi 60 mg LAR i.m. q 28 days 1200 μg s.c. t.id. fi 80 mg LAR i.m. q 28 days In addition, all patients will keep the treatment with pasireotide s.c. during the first 2 weeks of the LAR phase. The use of s.c. dosing during the initial 2 week period following the first LAR dose provides an appropriate level of medication during the LAR nadir.

Pasireotide, will be administered to all patients by s.c. injection, beginning with a dose of 300 μg administered three times daily (t.i.d.) for 2 weeks. If no pasireotide-related clinically meaningful/uncontrolled grade 3 or grade 4 adverse events occur the dose will be administered to all patients at an increased dose of 600 μg t.i.d. for 2 weeks, followed by 2 weeks of 900 μg t.i.d. and followed by 2 weeks of 1200 μg t.i.d. After the 8 weeks period, patients will be kept on treatment drug (highest dose without clinically meaningful/uncontrolled AEs) , switched to the corresponding pasireotide LAR dose and followed up for an extra 6 months.

Pasireotide sub-cutaneous formulation

Pasireotide lon acting release formulation

Novartis Pharmaceuticals

This study will evaluate the preliminary safety, pharmacokinetics, and anti-tumor activity of pasireotide s.c. in patients with metastatic melanoma or metastatic Merkel cell carcinoma. The study consists of three phases: screening, intra-patient dose-escalation, and follow-up phases.

In the screening phase patient will be informed of all aspects of the study and sign informed consent forms and then be screened for study eligibility.

During the intra-patient dose escalation phase, 18 patients will be treated with pasireotide s.c. 300 μg t.i.d. for 2 weeks. If there are no unacceptable AEs, defined as drug-related clinically meaningful, uncontrolled grade 3 or any grade 4 toxicities, patients will be dose escalated to 600 μg t.i.d. for 2 more weeks, then 900 μg t.i.d. for 2 weeks and then 1200 μg for 2 weeks provided that there are no unacceptable AEs. Each patient will be in the dose escalation phase for a maximum of 8 weeks.

At end of the intra-patient dose escalation phase, patients will be allowed to switch to 80 mg pasireotide LAR i.m. q 28 d (or a lower dose in case of toxicity) for an additional 6 months or until disease progression, or unacceptable AEs, or patient withdraws consent. In addition, all patients will keep their pasireotide s.c. t.i.d. treatment (same dose as that at the end of the 8-week dose escalation phase) during the first 2 weeks of the LAR follow-up phase, except on the day receiving the first LAR dose because of an anticipated initial burst of drug release.

A Phase I, Exploratory, Intra-patient Dose Escalation Study to Investigate the Preliminary Safety, Pharmacokinetics, and Anti-tumor Activity of Pasireotide (SOM230) s.c.Followed by Pasireotide LAR in Patients With Metastaticmelanoma or Metastatic Merkel Cell Carcinoma

Number of patients with AEs (overall and by severity) SAEs according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Number of patients with laboratory abnormalities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Number of patients with ECG according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Number of patients with vital sign abnormalities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Tumor response as measured by DCR defined as the proportion of patients with best overall response of complete response (CR), partial response (PR) or stable response (SR) according to the RECIST Version 1.0 Criteria.

Pasireotide plasma concentrations will be summarized by dose and time and PK profile of pasireotide concentration over time will be generated by dose.

Melanoma response biomarkers (MIA, S100B) will be evaluated in pre- and post-treatment samples on all patients to assess the biochemical response to pasireotide as change from baseline at Day 8, 15, 22, 29, 36, 43, 50, 57, 113, 169 and 225.

PD and cellular effect makers in tumor Protein expression levels for different PD markers such as p4EBP-1, pS6, pAKT, pERK and for different cellular effect markers of proliferation and apoptosis (such as Ki67, cyclin D1, cleaved caspase, PARP), angiogenesis (such as microvessel density) and secretion (such as IGF-1 receptor); change from baseline of these markers at day 29 and 57.

Number of patients with AEs (overall and by severity) SAEs according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Number of patients with ECG abnormalities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Number of patients with laboratory abnormalities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Number of patients with vital sign abnormalities and changes in vital signs according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Carcinoma, Squamous Cell

Neoplasms, Squamous Cell

Antineoplastic Agents

Cetuximab

Avelumab

Antineoplastic Agents, Immunological

Patients receive avelumab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with avelumab failure will crossover to Arm II.

Patients receive cetuximab IV over 1-2 hours on days 1, 8,15, and 22 and avelumab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles for cetuximab and 24 cycles for avelumab in the absence of disease progression or unacceptable toxicity.

Dan P. Zandberg, MD

This phase II trial studies how well avelumab with or without cetuximab work in treating patients with skin squamous cell cancer that has spread to other places in the body. Immunotherapy with monoclonal antibodies, such as avelumab and cetuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVES:

I. To evaluate whether treatment with avelumab plus cetuximab prolongs progression free survival (PFS) compared to avelumab alone.

SECONDARY OBJECTIVES:

I. To evaluate the confirmed objective response rate of each treatment arm. II. To evaluate the clinical benefit rate of each treatment arm. III. To evaluate the PFS of cetuximab plus avelumab in patients that have progressed on single agent avelumab.

IV. To evaluate the overall survival (OS) for each treatment arm. V. To evaluate toxicity across treatment arms of avelumab plus cetuximab and avelumab alone.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive avelumab intravenously (IV) over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with avelumab failure will crossover to arm II.

ARM II: Patients receive cetuximab IV over 1-2 hours on days 1, 8,15, and 22 and avelumab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles for cetuximab and 24 cycles for avelumab in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months until disease progression, then every 6 months for up to 2 years.

Avelumab With or Without Cetuximab in Treating Patients With Advanced Skin Squamous Cell Cancer

Phase II Randomized Trial of Avelumab Plus Cetuximab Versus Avelumab Alone in Advanced Cutaneous Squamous Cell Carcinoma of the Skin (cSCC)

The study will be declared promising if, after the 37th PFS event, the hazard ratio is less than 0.758.

A patient will be declared a success for RR if they achieve a partial response (PR) or better on two consecutive evaluations (at least 8 weeks apart). The number of successes will be divided by the number of evaluable patients to estimate the RR for each treatment arm and exact 95% confidence intervals will be calculated based on the properties of the binomial distribution.

The CBR is will be estimated as the number of successes divided by the total number of evaluable patients. An exact 95% confidence interval will be constructed around the CBR using the properties of the binomial distribution.

Will explore the PFS for those patients that crossover to combination therapy (avelumab + cetuximab) after progressing on avelumab alone (baseline time being the time of crossover). The Kaplan-Meier method will be used to calculate a median PFS as well as a 95% confidence interval.

The Kaplan-Meier method will be used to calculate a median OS as well as a 95% confidence interval.

Will be described and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Maximum grade adverse events will be summarized in a tabular setting by treatment arm.

National Cancer Institute (NCI)

Alliance for Clinical Trials in Oncology

Neoplasm Metastasis

Antibodies

Nivolumab

Ipilimumab

Immunoglobulins

Immune Checkpoint Inhibitors

Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity.

Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Stereotactic Body Radiation Therapy (SBRT) to be given at the start of week 2.

Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks.

Stereotactic Body Radiation Therapy 24Gy in 3 fractions.

Stereotactic Body Radiation Therapy (SBRT)

Evan Wuthrick, M.D

The purpose of this study is to test the effectiveness, safety, and tolerability of the drugs nivolumab plus ipilimumab with or without the addition of stereotactic body radiation therapy (SBRT). Nivolumab is an antibody (a type of human protein) that is being tested to see if it will stimulate the body's immune system to work against tumor cells. This study will test an investigational use of nivolumab.

Participants are randomly assigned in a 1:1 ratio to Arm A (nivolumab + ipilimumab), or Arm B (nivolumab + ipilimumab + SBRT).

Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma

A Phase 2, Randomized, Multi-institutional Study of Nivolumab and Ipilimumab Versus Nivolumab, Ipilimumab and Stereotactic Body Radiation Therapy for Metastatic Merkel Cell Carcinoma

Overall response according to Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) including Complete Response (CR) + Partial Response (PR).

Median Progression Free Survival with 95% Confidence Interval. Progression is defined as progressive tumor lesions per immune-related Response Evaluation in Solid Tumors (irRECIST) definition, or appearance of one or more new Merkel cell carcinoma lesions, which can be local or distant in location from the irradiated lesions.

Median Overall Survival with 95% Confidence Interval. The length of time from the start of treatment until death from any cause.

Bristol-Myers Squibb

H. Lee Moffitt Cancer Center and Research Institute

Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity.

Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks.

Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks.

Arm A: Nivolumab + Ipilimumab

Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Stereotactic Body Radiation Therapy (SBRT) to be given at the start of week 2.

Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks.

Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks.

Stereotactic Body Radiation Therapy (SBRT): Stereotactic Body Radiation Therapy 24Gy in 3 fractions.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1-2 of ST316 With Selected Advanced Unresectable and Metastatic Solid Tumors	NCT05848739	Breast Cancer M... Pancreatic Canc... NSCLC, Metastat... Synovial Sarcom... Colon Cancer Metastatic Colo... Melanoma Recurr... Metastatic Skin... Melanoma Stage ... Triple Negative... TNBC - Triple-N... Cholangiocarcin... Ovarian Cancer Metastatic Mela... Hepatocellular ...	ST316	18 Years -	Sapience Therapeutics
A Phase I, Exploratory, Intra-patient Dose Escalation Study to Investigate the Preliminary Safety, Pharmacokinetics, and Anti-tumor Activity of Pasireotide (SOM230) s.c.Followed by Pasireotide LAR in Patients With Metastaticmelanoma or Metastatic Merkel Cell Carcinoma	NCT01652547	Metastatic Mela...	Pasireotide sub... Pasireotide lon...	18 Years -	Novartis
A Phase 1-2 of ST316 With Selected Advanced Unresectable and Metastatic Solid Tumors	NCT05848739	Breast Cancer M... Pancreatic Canc... NSCLC, Metastat... Synovial Sarcom... Colon Cancer Metastatic Colo... Melanoma Recurr... Metastatic Skin... Melanoma Stage ... Triple Negative... TNBC - Triple-N... Cholangiocarcin... Ovarian Cancer Metastatic Mela... Hepatocellular ...	ST316	18 Years -	Sapience Therapeutics
Avelumab With or Without Cetuximab in Treating Patients With Advanced Skin Squamous Cell Cancer	NCT03944941	Skin Squamous C... Metastatic Skin...	Avelumab Cetuximab	18 Years -	Alliance for Clinical Trials in Oncology
Avelumab With or Without Cetuximab in Treating Patients With Advanced Skin Squamous Cell Cancer	NCT03944941	Skin Squamous C... Metastatic Skin...	Avelumab Cetuximab	18 Years -	Alliance for Clinical Trials in Oncology
Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma	NCT03071406	Merkel Cell Car... Skin Cancer	Nivolumab Ipilimumab Stereotactic Bo...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma	NCT03071406	Merkel Cell Car... Skin Cancer	Nivolumab Ipilimumab Stereotactic Bo...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for metastatic skin cancer