TRC102 and Temozolomide for Relapsed Solid Tumors and Lym... | NCT01851369

ID	Type	Description	Link
13-C-0118

Description Module

Detailed Description

Background:

Base excision repair (BER) of deoxyribonucleic acid (DNA) repair pathway has been implicated in resistance to both alkylating and antimetabolite chemotherapy.
TRC102 (methoxyamine hydrochloride (HCl) acts through a novel mechanism to inhibit BER and has demonstrated the ability to potentiate the activity of the alkylating agent temozolomide (TMZ), in vitro and in vivo. We hypothesize that TRC102 can be safely co-administered with TMZ and would potentiate DNA damage caused by TMZ, resulting in antitumor responses.
Based on responses measured during the Phase I portion of the trial, we will further explore the efficacy of this combination in patients with metastatic colon carcinoma, non-small cell lung cancer (NSCLC), and granulosa cell ovarian cancer

Primary Objective:

To establish the safety, tolerability, and maximum tolerated dose (MTD) of oral TRC102 in combination with oral TMZ in patients with refractory solid tumors
Evaluate the pharmacokinetic (PK) profile of oral TRC102 when administered in combination with TMZ.
To explore the response rate of this combination in patients with colon cancer, NSCLC, and granulosa cell ovarian cancer

Secondary Objective:

-To explore the progression free survival rate of this combination in patients with colon cancer, NSCLC, and granulosa cell ovarian cancer

Exploratory Objectives:

Investigate tumor genomic and transcriptomic alterations potentially associated with sensitivity and/or the development of resistance to TRC102 and temozolomide.
Determine the effects of the study treatment on the level of histone gamma-H2A histone family member X (H2AX) in circulating tumor cells (CTCs) and tumor and correlate the gamma-H2AX response in tumor and CTCs
Determine the effects of the study treatment on the levels of cleaved caspase 3, epithelial- mesenchymal transition, and abdominoperineal excision (APE) in tumor and CTCs
Determine and characterize the effects of study treatment on erythrocytes
Characterize the clinical presentation of hemolysis observed in earlier study subjects and explore the possible mechanisms

Eligibility:

Phase I: histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist
Phase II: histologically confirmed adenocarcinoma of the colon post at least two lines of therapy, NSCLC post at least two lines of therapy, or granulosa cell ovarian cancer post at least one line of therapy
No major surgery, radiation, or chemotherapy within 4 weeks prior to entering the study
Adequate organ function
Healthy adult volunteers greater than or equal to 18 years of age will be consented to donate research blood

Please note: healthy adult volunteers will no longer be recruited to provide blood for this study as we will no longer perform the hemolysis analysis.

Study Design: Phase I

This is an open-label Phase I trial; traditional 3+3 design.
Oral TRC102 and oral TMZ will be administered daily, days 1-5 in 28-day cycles
Once the MTD is established, up to 15 additional patients will be enrolled at the MTD to further evaluate that dose for PK and pharmacodynamic (PD) endpoints for evidence of DNA damage and apoptosis.
During the escalation phase, tumor biopsies will be optional. During the expansion phase, (once MTD is reached), mandatory paired tumor biopsies will be pursued in the 15 additional patients enrolled to further evaluate progressive disease (PD) endpoints.

Phase II

This is a 3-arm Simon 2-stage design trial evaluating independently the response rate of patients with colon, NSCLC, and granulosa cell ovarian cancer.
Patients with a body surface area (BSA) of greater than or equal to 1.6 m(2) will receive 125 mg of TRC 102 and 150 mg/m(2) of TMZ PO qday x 5 every 28 days (DL6). Patients with a BSA of <1.6 m(2) will receive 100 mg of TRC 102 and 150 mg/m(2) of TMZ by mouth (PO) every (q)day x 5 every 28 days (Dose Level (DL)5). Each cycle will be 28 days.
The accrual ceiling for the Phase II portion is 75 patients.
Mandatory paired tumor biopsies will be pursued to further evaluate PD endpoints.

Label	Type	Description	Intervention Names
Combination Treatment with Oral methoxyamine hydrochloride (TRC102) and oral Temozolomide (TMZ)	Experimental	Combination treatment with oral methoxyamine hydrochloride (TRC102) and oral Temozolomide (TMZ) for days 1-5 of 28-day cycles.	Drug: TRC102 Diagnostic Test: CT scan Other: Lomotil Other: Prochlorperazine Other: Metoclopramide Other: 5-HT3 antagonist Other: Aprepitant Procedure: Biopsy

Name	Type	Description	Arm Group Labels	Other Names
TRC102	Drug	Methoxyamine hydrochloride (TRC102) has been shown to potentiate the activity of temozolomide by preventing base excision repair (BER) and allowing cleavage of TRC102 bound deoxyribonucleic acid (DNA), which will cause DNA strand breaks in cancer cells. We hypothesize that oral TRC102 can be safely co-administered with Temozolomide (TMZ) and would potentiate DNA damage caused by TMZ resulting in antitumor responses.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Phase 2: Response Rate of This Combination in Participants With Colon Cancer, Non-small Cell Lung Cancer (NSCLC), and Granulosa Cell Ovarian Cancer	Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on-study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.	Response rate at one year
The Number of Dose Limiting Toxicities Observed in Participants Receiving Oral TRC102 in Combination With Oral TMZ	Dose-limiting toxicities (DLTs) are defined as toxicities occurring within the first cycle of treatment felt to be possibly, probably, or definitely related to administration of study drugs and fulfilling one of the following criteria: Grade 4 neutropenia, febrile neutropenia, neutropenic infection: Grade ≥ 3 neutropenia with grade ≥ 3 infection, Grade ≥ 3 thrombocytopenia, a drop in hemoglobin (Hgb) ≥3.0 g/dL over one week, and all Grade ≥ 3 non-hematologic toxicity other than: non-bloody diarrhea Grade 3 that is corrected to Grade ≤ 2 within 24 hours, nausea and vomiting Grade 3 that is corrected to Grade ≤ 1 within 24 hours, creatinine Grade 3 corrected to Grade ≤ 1 within 48 hours, and Grade 3 electrolyte abnormalities. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event.	At dose-limiting toxicity (DLT) determined in the first cycle; approximately 28 days
Phase 1 Pharmacokinetic (PK) Profile of Oral TRC102 When Administered in Combination With Temozolomide (TMZ) as Measured by Maximum Plasma Concentration (Cmax) of TRC102: Mean (Standard Deviation)

Secondary Outcomes

Measure	Description	Time Frame
Phase 2: Progression Free Survival Rate of This Combination in Participants With Colon Cancer, Non-small Cell Lung Cancer (NSCLC), and Granulosa Cell Ovarian Cancer	Progression free survival rate of this combination in participants with colon cancer, NSCLC, and granulosa cell ovarian cancer. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) and is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum onstudy (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.

Other Outcomes

Measure	Description	Time Frame
Phase 1 and Phase 2: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Eligibility Module

Eligibility Criteria

Eligibility Criteria (Patients)
Phase I: histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist.
Phase II: histologically confirmed colorectal adenocarcinoma post at least two lines of therapy, non-small cell lung cancer (NSCLC) post at least two lines of therapy, or granulosa cell ovarian cancer post at least one line of therapy. Patients must have measurable disease.
Age greater than18 years. Because no dosing or adverse event data are currently available on the use of methoxyamine hydrochloride (TRC102) in combination with Temozolomide (TMZ) in patients less than 18 years of age, children are excluded from this study.
Patients enrolling in the expansion cohorts must have disease amenable to biopsy and be willing to undergo pre-and post-treatment biopsies.
Eastern Cooperative Oncology Group (ECOG) performance status less than 2 (Phase I), less than or equal to 1(Phase II).
Life expectancy of greater than 3 months
Patients must have normal organ and marrow function as defined below:
Absolute neutrophil count greater than 1,500/mcL
Hemoglobin greater than or equal to 10 g/dL without transfusion within 1 week prior to enrollment

Platelets greater than or equal to 100,000/mcL

Total bilirubin less than or equal to1.5 X institutional ULN

Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine transaminase (ALT) serum glutamic-pyruvic transaminase (SGPT)(SGPT) less than or equal to 3 X institutional upper limit of normal; 5.0 x upper limit of normal (ULN) in cases of liver metastases

creatinine less than or equal to 1.5 X institutional ULN

creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels greater than 1.5 mg/dL

-The effects of study drug on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for at least 3 months after dosing with study drugs ceases. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of study drug administration.

Patients must have completed any chemotherapy, radiation therapy, or biologic therapy greater than or equal to 4 weeks (or 5 half-lives, whichever is shorter) prior to entering the study (6 weeks for nitrosoureas or mitomycin C). Patients must be greater than or equal to 2 weeks since any prior administration of a study drug in a Phase 0 or equivalent study and greater than or equal to 1 week from palliative radiation therapy. Patients must have recovered to eligibility levels from prior toxicity or adverse events. Treatment with bisphosphonates is permitted.
Patients must be able to swallow whole tablets or capsules; nasogastric or gastric (G)-tube administration is not allowed.
Ability to understand and the willingness to sign a written informed consent document and to undergo tumor biopsies in the expansion phase.

Exclusion Criteria (Patients)

Patients who are actively receiving any other investigational agents.
Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for greater than or equal to 4 weeks without requiring steroid and anti-seizure medications are eligible to participate.
Phase II only: No other prior malignancies are allowed except for the following:
- Adequately managed stage 0 (carcinoma in situ), I, or II basal cell or squamous cell carcinoma from which the patient is currently in complete remission.
- Any other cancer from which the patient has been disease-free for three years.
- Adequately managed stage I or II well differentiated thyroid or prostate cancer is also eligible, wherein the patient is not required to be in complete remission.
Phase II only: patients with colorectal cancer with known MSI-high disease who have not previously been treated with immunotherapy or who have refused treatment with immunotherapy.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to TRC102 or TMZ.
Uncontrolled intercurrent illness including, but not limited to, serious untreated infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded from this study because the effects of the study drugs on the developing fetus are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued prior to the first dose of study drug and women should refrain from nursing throughout the treatment period and for 3 months following the last dose of study drug.
HIV-positive patients on combination antiretroviral therapy are ineligible because of possible pharmacokinetic (PK) interactions with TRC102.

(Healthy volunteer blood donors)

Please note: healthy adult volunteers will no longer be recruited to provide blood for this study as we will no longer perform the hemolysis analysis.

Age greater than 18 years; hemoglobin greater than or equal to 12 g/dL; no history of bleeding problems; not taking aspirin or any medication that may affect erythrocyte biochemistry
Willingness to sign the healthy volunteer informed consent form.

Name	Affiliation	Role
Alice P Chen, M.D.	National Cancer Institute (NCI)	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
National Institutes of Health Clinical Center		Bethesda	Maryland	20892	United States

PubMed Identifier	Type	Citation	Retractions
12231545	Background	Liu L, Nakatsuru Y, Gerson SL. Base excision repair as a therapeutic target in colon cancer. Clin Cancer Res. 2002 Sep;8(9):2985-91.
17332299	Background	Yan L, Bulgar A, Miao Y, Mahajan V, Donze JR, Gerson SL, Liu L. Combined treatment with temozolomide and methoxyamine: blocking apurininc/pyrimidinic site repair coupled with targeting topoisomerase IIalpha. Clin Cancer Res. 2007 Mar 1;13(5):1532-9. doi: 10.1158/1078-0432.CCR-06-1595.

Label	URL
NIH Clinical Center Detailed Web Page	View source

Arm/Group Information

ID	Title	Description
FG000	Phase (Ph) 1 Dose Level -2 Methoxyamine (TRC102) 25mg & Temozolomide (TMZ) 75mg/m^2	No participants were enrolled in this group. Cycle = 28 days; Methoxyamine (TRC102) 25mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 75mg/m^2 PO QD on days 1-5.
FG001	Phase 1 Dose Level -1 Methoxyamine (TRC102) 25mg & Temozolomide 100mg/m^2	No participants were enrolled in this group. Cycle = 28 days; Methoxyamine (TRC102) 25mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 100mg/m^2 PO QD on days 1-5.
FG002	Phase 1 Solid Tumor Dose Level 1 Methoxyamine (TRC102) 125mg & Temozolomide 75mg/m^2	Cycle = 28 days; Methoxyamine (TRC102) 125mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 75mg/m^2 PO QD on days 1-5.
FG003	Phase 1 Solid Tumor Dose Level 2 Methoxyamine (TRC102) 50mg & Temozolomide 125mg/m^2	Cycle = 28 days; Methoxyamine (TRC102) 50mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 125mg/m^2 PO QD on days 1-5.
FG004	Phase 1 Solid Tumor Dose Level 3 Methoxyamine (TRC102) 50mg & Temozolomide 150mg/m^2	Cycle = 28 days; Methoxyamine (TRC102) 50mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5.
FG005	Phase 1 Solid Tumor Dose Level 4 Methoxyamine (TRC102) 75mg & Temozolomide 150mg/m^2	Cycle = 28 days; Methoxyamine (TRC102) 75mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5.
FG006	Phase 1 Solid Tumor Dose Level 5 Methoxyamine (TRC102) 100mg & Temozolomide 150mg/m^2	Cycle = 28 days; Methoxyamine (TRC102) 100mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5.
FG007	Phase 1 Solid Tumor Dose Level 6 Methoxyamine (TRC102) 125mg & Temozolomide 150mg/m^2	Cycle = 28 days; Methoxyamine (TRC102) 125mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5.
FG008	Phase 1 Solid Tumor Dose Level 7 Methoxyamine (TRC102) 150mg & Temozolomide 150mg/m^2	Cycle = 28 days; Methoxyamine (TRC102) 150mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5.
FG009	Phase 1 Solid Tumor Dose Level 8 Methoxyamine (TRC102) 150mg & Temozolomide 200mg/m^2	Cycle = 28 days; Methoxyamine (TRC102) 150mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 200mg/m^2 PO QD on days 1-5.
FG010	Ph 2 Colorectal Cancer TMZ 150mg/m^2/Methoxyamine 125mgOR100mg(Based on Body Surface Area)	Cycle = 28 days; Methoxyamine (TRC102) 125mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5 for participants with a body surface area (BSA) ≥ 1.6 m^2 OR Cycle = 28 days; Methoxyamine (TRC102) 100mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5 for participants with a body surface area (BSA) < 1.6 m^2.
FG011	Ph2 Non Small Cell Lung Cancer TMZ 150mg/m^2/Methoxyamine125mgOR100mg(Based on Body Surface Area)	Cycle = 28 days; Methoxyamine (TRC102) 125mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5 for participants with a body surface area (BSA) ≥ 1.6 m^2 OR Cycle = 28 days; Methoxyamine (TRC102) 100mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5 for participants with a body surface area (BSA) < 1.6 m^2.
FG012	Ph 2 Granulosa Cell Temozolomide 150mg/m^2 & Methoxyamine 125mgOR 100mg (Based on Body Surface Area)	Cycle = 28 days; Methoxyamine (TRC102) 125mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5 for participants with a body surface area (BSA) ≥ 1.6 m^2 OR Cycle = 28 days; Methoxyamine (TRC102) 100mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5 for participants with a body surface area (BSA) < 1.6 m^2.

ID	Title	Description
BG000	Phase 1 Solid Tumor Dose Level 1 Methoxyamine (TRC102) 125mg & Temozolomide 75mg/m^2	Cycle = 28 days; Methoxyamine (TRC102) 125mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 75mg/m^2 PO QD on days 1-5.
BG001	Phase 1 Solid Tumor Dose Level 2 Methoxyamine (TRC102) 50mg & Temozolomide 125mg/m^2

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	Phase 2: Response Rate of This Combination in Participants With Colon Cancer, Non-small Cell Lung Cancer (NSCLC), and Granulosa Cell Ovarian Cancer	Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on-study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.	A total of 41/93 participants were analyzed: 0/52 phase 1 participants were analyzed as this outcome measure was for the phase 2 participants only; 41/41 phase 2 participants were evaluable for response rate.	Posted		Count of Participants		Participants		Response rate at one year

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1 Solid Tumor Dose Level 1 Methoxyamine (TRC102) 125mg & Temozolomide 75mg/m^2	Cycle = 28 days; Methoxyamine (TRC102) 125mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 75mg/m^2 PO QD on days 1-5.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Abdominal pain	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Abdominal distension	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment

Title	Organization	Phone	Extension	Email
Dr. Alice P.Chen	National Cancer Institute	2407813320		chenali@mail.nih.gov

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jul 6, 2022	Nov 21, 2023	Prot_SAP_000.pdf
ICF	No	No	Yes	Informed Consent Form: Cohort Treatment Consent	Jul 22, 2022	Nov 21, 2023	ICF_001.pdf
ICF	No	No	Yes	Informed Consent Form: Healthy Blood Donor Consent	May 7, 2019	Nov 21, 2023	ICF_002.pdf
ICF	No	No	Yes	Informed Consent Form: Standard Phase I Consent	Sep 5, 2017	Nov 22, 2023	ICF_003.pdf

ID	Term
D008223	Lymphoma
D003110	Colonic Neoplasms

ID	Term
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases

ID	Term
C005214	methoxyamine
D014057	Tomography, X-Ray Computed
C002534	atropine sulfate-diphenoxylate hydrochloride drug combination
D011346	Prochlorperazine
D008787	Metoclopramide
D058831	Serotonin 5-HT3 Receptor Antagonists
D012701	Serotonin
D000077608	Aprepitant
D001706	Biopsy

ID	Term
D007090	Image Interpretation, Computer-Assisted
D003952	Diagnostic Imaging
D019937	Diagnostic Techniques and Procedures
D003933	Diagnosis

ID	Title	Description
OG000	Ph 2 Colorectal Cancer TMZ 150mg/m^2/Methoxyamine 125mgOR100mg(Based on Body Surface Area)	Cycle = 28 days; Methoxyamine (TRC102) 125mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5 for participants with a body surface area (BSA) ≥ 1.6 m^2 OR Cycle = 28 days; Methoxyamine (TRC102) 100mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5 for participants with a body surface area (BSA) < 1.6 m^2.
OG001	Ph2 Non Small Cell Lung Cancer TMZ 150mg/m^2/Methoxyamine125mgOR100mg(Based on Body Surface Area)	Cycle = 28 days; Methoxyamine (TRC102) 125mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5 for participants with a body surface area (BSA) ≥ 1.6 m^2 OR Cycle = 28 days; Methoxyamine (TRC102) 100mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5 for participants with a body surface area (BSA) < 1.6 m^2.
OG002	Ph 2 Granulosa Cell Temozolomide 150mg/m^2 & Methoxyamine 125mgOR 100mg (Based on Body Surface Area)	Cycle = 28 days; Methoxyamine (TRC102) 125mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5 for participants with a body surface area (BSA) ≥ 1.6 m^2 OR Cycle = 28 days; Methoxyamine (TRC102) 100mg by mouth (PO) everyday (QD) on days 1-5; Temozolomide (TMZ) 150mg/m^2 PO QD on days 1-5 for participants with a body surface area (BSA) < 1.6 m^2.