Neoplasms

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Rectal Neoplasms

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Gastrointestinal Diseases

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Leucovorin

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Levoleucovorin

Oxaliplatin

Folic Acid

Folinic Acid

Folate

Vitamin B9

Radiochemotherapy followed by consolidation chemotherapy. Deep regional hyperthermia can additionally be performed at the centers in Tübingen and Erlangen.

Radiotherapy: 28 x 1.8 Gy (total: 50.4 Gy), 5 fractions per week on day 1- 38

Radiotherapy

chemoradiotherapy is started according to the following schedule: 5-FU: 250 mg/sqm per day, iv, on day 1-14, day 22-35; Oxaliplatin: 50 mg/sqm, day 1, 8, 22, and 29. After a break of two and a half weeks, patients receive three chemotherapy cycles, starting on day 57, 71 and 85, consisting of: Folinic acid: 400 mg/sqm, 2h-iv; Oxaliplatin: 100 mg/sqm, 2h-iv; 5-FU: 2400 mg/sqm, 46h-iv

Chemotherapy

Deep regional hyperthermia to the pelvis, total time 90 min, target temperature 41-42°C. Twice weekly, up to a total of 10 sessions within d1 and d38.

Deep regional hyperthermia is offered at the centers in Tübingen and Erlangen.

Deep regional hyperthermia

Cihan Gani, Dr.

Daniel Zips, Prof.

Oliver Ott, Prof.

Claus Rödel, Prof.

Bülent Polat, Dr.

There is a growing body of evidence that surgery and associated morbidities can be omitted without compromising oncological safety in selected patients who have achieved a clinical complete response after radiochemotherapy. However with standard neoadjuvant treatment regimens the pathological complete response rate lies in the range between 10%-20%, the number of patients qualifying for non-operative management is even lower since the sensitivity of currently available diagnostic measures for predicting the pathological complete response hardly surpasses 50%-60%.The hereby proposed phase II trial CAO/ARO/AIO-16 aims at finding novel and innovative aspects of rectal cancer treatment. According to recently published data the radiochemotherapy regime in the present study with consolidating chemotherapy and delayed assessment of response has the potential to achieve pathological complete rates of approximately 40%. A standardized re-evaluation after consolidating chemotherapy will select patients who are candidates for organ-preservation. These patients will not undergo radical surgery and will instead be follow-up closely for tumor regrowth.

Patients will undergo different treatments based on response achieved after radiochemotherapy.

1. Clinical Complete Response: Omission of surgery and follow-up
2. Near clinical complete response: Reevaluation in three months
3. Poor / no response: Surgery

Organ Preservation in Locally Advanced Rectal Cancer by Radiochemotherapy Followed by Consolidation Chemotherapy.

Organ Preservation in Locally Advanced Rectal Cancer by Radiochemotherapy Followed by Consolidation Chemotherapy. A Prospective Phase II Pilot Trial of the German Rectal Cancer Study Group

Response to treatment is assessed on day 106 after the start of radiochemotherapy.

A clinical complete response is defined by standardized findings in rectoscopy, MRI and digital rectal examination

Possible scores range from 0 (perfect continence) to 24 (complete incontinence)

University Hospital Tuebingen

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Lung Neoplasms

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Prostatic Neoplasms

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Stomach Neoplasms

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Recurrence

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Carcinoma, Ovarian Epithelial

Cholangiocarcinoma

Urinary Bladder Neoplasms

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Carcinoma, Renal Cell

Liver Neoplasms

Head and Neck Neoplasms

Skin Neoplasms

Mouth Neoplasms

Salivary Gland Neoplasms

Laryngeal Diseases

Adenocarcinoma, Mucinous

Cystadenocarcinoma

Carcinoma, Mucoepidermoid

Mucoepidermoid Tumor

Bile Duct Neoplasms

Tongue Neoplasms

Laryngeal Neoplasms

Urologic Neoplasms

Lip Neoplasms

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Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

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Disease Attributes

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

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Male Urogenital Diseases

Stomach Diseases

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Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urologic Diseases

Kidney Neoplasms

Kidney Diseases

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Stomatognathic Diseases

Salivary Gland Diseases

Biliary Tract Neoplasms

Bile Duct Diseases

Biliary Tract Diseases

Neoplasms, Cystic, Mucinous, and Serous

Tongue Diseases

Otorhinolaryngologic Neoplasms

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Otorhinolaryngologic Diseases

Oropharyngeal Neoplasms

Pharyngeal Neoplasms

Pharyngeal Diseases

Stomach Cancer

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Bile Duct Cancer

Renal Cell Carcinoma

Oral Cancer

Adenocarcinoma of the Appendix

Tongue Cancer

Mucoepidermoid Carcinoma

Antibodies

Immunoglobulins

Mitogens

Six dose levels have been selected for evaluation in the Phase I part of the study: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg of A166

HER2 positive (Immunohistochemistry (IHC) 2+ with fluorescence in situ hybridization (FISH) confirmation and Immunohistochemistry (IHC) 3+) breast cancer. Treatment with A166 at recommended Phase II dose.

HER2 positive (Immunohistochemistry (IHC) 2+ with fluorescence in situ hybridization (FISH) confirmation and Immunohistochemistry (IHC) 3+) gastric cancer. Treatment with A166 at recommended Phase II dose.

HER2 low expressing (Immunohistochemistry (IHC) 1+ and IHC 2+ without fluorescence in situ hybridization (FISH) confirmation) breast cancer. Treatment with A166 at recommended Phase II dose.

All cancers other than breast cancer with low HER2 expression (Immunohistochemistry (IHC) 1+ and IHC 2+ without fluorescence in situ hybridization (FISH) confirmation) and HER2 positive (IHC2+ with FISH confirmation and Immunohistochemistry (IHC) 3+) cancers other than breast and gastric cancer. Treatment with A166 at recommended Phase II dose.

A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells.

A166

Jordi Rodon Ahnert, MD, PhD

Open-label, Phase I-II, first-in-human (FIH) study for A166 monotherapy in HER2-expressing or amplified patients who progressed on or did not respond to available standard therapies. Patients must have documented HER2 expression or amplification. The patient must have exhausted available standard therapies. Patients will receive study drug as a single IV infusion. Cycles will continue until disease progression or unacceptable toxicity.

This is an open-label, Phase I-II, first-in-human (FIH) study for A166 as monotherapy in HER2-expressing patients who progressed on or did not respond to available standard therapies. Patients enrolled in this Phase III study must have documented HER2 positivity defined as positive on in situ hybridization (ISH) or next-generation sequencing (NGS) or HER2 expression, defined as at least 1+ by validated immunohistochemistry (IHC) test. The patient must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have ceased to provide clinical benefit for their disease. Patients will receive study drug as a single IV infusion at the prescribed dose level in each treatment cycle. Cycles will continue until disease progression or unacceptable toxicity. The study is divided into 2 parts (Phase I and Phase II).

Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene

A Phase I-II, FIH Study of A166 in Locally Advanced/Metastatic Solid Tumors Expressing Human Epidermal Growth Factor Receptor 2 (HER2) or Are HER2 Amplified That Did Not Respond or Stopped Responding to Approved Therapies

Number of patients with dose limiting toxicities

Klus Pharma Inc.

WBC \<4.0×10\^9 14 days after radiotherapy

WBC \<4.0×10\^9 90 days after radiotherapy

MRI including T1WI, DWI sequence and IDEAL-IQ sequence before radiotherapy, 1-2 weeks after radiotherapy and 90 days after radiotherapy were performed

The blood routine was collected before radiotherapy, 1 week, 2 weeks and 90 days after radiotherapy.

blood routine test

宁 朗, Professor

Ning 朗, Professor

Ning Lang

Ning Lang, Professor

Rectal cancer patients who received neoadjuvant chemoradiotherapy in Peking University Third Hospital in 2021 are divided into acute myelosuppression group, chronic myelosuppression group and normal group. The differences of magnetic resonance parameters between the groups were compared. The risk identification model of acute and chronic myelosuppression after neoadjuvant chemoradiotherapy was established by clinical risk factors and quantitative parameters of magnetic resonance imaging, and the prediction efficiency of the model was evaluated.

The patients with locally advanced rectal cancer diagnosed in Peking University Third Hospital and undergoing neoadjuvant chemoradiotherapy were collected. The basic information of patients (including age, sex, BMI, TNM stage of rectal cancer (T2, T3 stage)) was collected. The blood routine was collected before radiotherapy, 1 week, 2 weeks and 90 days after radiotherapy. MRI including T1WI, DWI sequence and IDEAL-IQ sequence before radiotherapy, 1-2 weeks after radiotherapy and 90 days after radiotherapy were performed, and the corresponding parameters were obtained. The white blood cell values and quantitative parameters of magnetic resonance (including T1WI, DWI signal intensity (b = 1000) and proton density fat fraction (PDFF) of sacrilium and proximal femur were collected. Patients were divided into acute myelosuppression group and non-acute myelosuppression group according to blood routine results 14 days after radiotherapy, and chronic myelosuppression group and non-chronic myelosuppression group according to blood routine results 90 days after radiotherapy. The magnetic resonance parameters difference between 1-2 weeks after radiotherapy and before radiotherapy, and the magnetic resonance parameters difference between 90 days after radiotherapy and before radiotherapy were calculated. By comparing the differences of clinical risk factors and quantitative parameters of MRI between the two groups, the meaningful variables were screened out, and the risk identification model of acute and chronic myelosuppression was established.

Application of MRI in Identifying Myelosuppression Risk of Neoadjuvant Chemoradiotherapy for Rectal Cancer

Application of MRI Quantitative Parameters in Identifying Myelosuppression Risk of Neoadjuvant Chemoradiotherapy for Rectal Cancer

The differences of PDFF(%) between the acute myelosuppression group and no suppression group

The differences of T1WI signal intensity（IU） between the acute myelosuppression group and no suppression group

The differences of DWI signal intensity（IU）between the acute myelosuppression group and no suppression group

The differences of ADC value（mm\^2/s) between the acute myelosuppression group and no suppression group

The differences of PDFF(%) between the chronic myelosuppression group and no suppression group

The differences T1WI signal intensity（IU）between the chronic myelosuppression group and no suppression group

The differences of DWI signal intensity（IU）between the chronic myelosuppression group and no suppression group

The differences of ADC value（mm\^2/s) between the chronic myelosuppression group and no suppression group

Peking University Third Hospital

Capecitabine

Antimetabolites

Drug: Neoadjuvant chemotherapy Capeox (Capecitabine + Oxaliplatin), 6 cycles; adjuvant chemotherapy, Capecitabine, 2 cycles or physicians' decision.

External beam radiotherapy: Neoadjuvant, 50 Gy, 2 Gy/session; 25 fractions. Procedure: 'Watch and wait strategy' or surgery including local excision, intersphincter resection or total mesorectal excision or other kinds of surgeries.

Capecitabine, Oxaliplatin

External beam radiotherapy to the primary tumor, regional lymph nodes and clinical target volume

External beam radiotherapy

'Local excision' or 'Intersphincter resection' or 'Total mesorectal excision' or other surgeries

Surgery

Watch and wait strategy recommendation and discussion for cCR patients

Watch and wait strategy

WeiWei Xiao

This is a open-label, single-arm study to investigate the safety and efficacy of total neoadjuvant treatment (TNT) in patients with locally advanced resectable rectal cancer.

Standard treatment of rectal cancer is neoadjuvant capecitabine chemotherapy with radiotherapy, followed by total mesorectal excision.

A new concept suggests organ preservation as an alternative to rectal excision in good responders after neoadjuvant radiochemotherapy to decrease surgical morbidity and increase quality of life.

The rational is the fact that 15%-20% of patients have sterilized tumours after chemoradiotherpay for locally advanced rectal cancer. As compared to capecitabine alone, oxaliplatin and more intensified chemotherapy have been shown to increase tumor regression in the neoadjuvant chemoradiation setting. Meanwhile, prolong of time interval from the end of radiotherapy to assessment of tumor response could further increase pathologic complete response rate and complete clinical response rate.

The objective of this trial is to increase the rate of clinical complete response for distal rectal cancer patients by optimizing tumour response. The investigators expect to increase chance of clinical complete response by using total neoadjuvant treatment regimen as compared to conventional chemoradiotherapy alone.

TNT to Increase the Clinical Complete Response Rate for Distal LARC

Total Neoadjuvant trEatment to Increase the Clinical Complete reSponse Rate for diStal Locally Advanced Rectal Cancer (TESS)

Number of patients with sphincter preservation through Watch and wait strategy, or local excision, or intersphincter resection, or low anterior resection, etc.

Rate of pathological complete response and tumor regression grade distribution

Long-term anal function according to Wexner Continence Grading Scale

Long-term toxicity grading according to CTCAE 5.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Organ Preservation in Locally Advanced Rectal Cancer by Radiochemotherapy Followed by Consolidation Chemotherapy.	NCT03561142	Rectal Cancer Rectal Neoplasm... Rectal Cancer S... Rectal Cancer S...	Radiotherapy Chemotherapy Deep regional h...	18 Years -	University Hospital Tuebingen
Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene	NCT03602079	HER2-positive B... HER2 Gene Mutat... HER-2 Gene Ampl... HER2 Positive G... Salivary Gland ... Salivary Gland ... Salivary Gland ... Salivary Gland ... Lung Cancer Colo-rectal Can... Rare Diseases Solid Tumor Recurrent Gastr... Recurrent Colon... Recurrent Breas... Head and Neck C... Head and Neck C... Bladder Cancer Cervical Cancer Liver Cancer Bile Duct Cance... Urologic Cancer Pancreatic Canc... Prostate Cancer Recurrent Prost... Rectal Cancer Recurrent Ovari... Recurrent Renal... Rectal Cancer S... Rectal Cancer S... Rectal Cancer S... Skin Cancer Mouth Cancer Lip Cancer Stag... Tongue Cancer Breast Neoplasm... Larynx Cancer Tonsil Cancer Palate Cancer Mucoepidermoid ... Primary Periton... Mucinous Adenoc... Mucinous Breast... Cholangiocarcin...	A166	18 Years -	Klus Pharma Inc.
Organ Preservation in Locally Advanced Rectal Cancer by Radiochemotherapy Followed by Consolidation Chemotherapy.	NCT03561142	Rectal Cancer Rectal Neoplasm... Rectal Cancer S... Rectal Cancer S...	Radiotherapy Chemotherapy Deep regional h...	18 Years -	University Hospital Tuebingen
Application of MRI in Identifying Myelosuppression Risk of Neoadjuvant Chemoradiotherapy for Rectal Cancer	NCT04970498	Rectal Cancer S... Rectal Cancer S...	MRI blood routine t...	-	Peking University Third Hospital
TNT to Increase the Clinical Complete Response Rate for Distal LARC	NCT03840239	Rectal Cancer Rectal Cancer S... Rectal Cancer S... Chemoradiation	Capecitabine, O... External beam r... Surgery Watch and wait ...	18 Years - 70 Years	Sun Yat-sen University
Application of MRI in Identifying Myelosuppression Risk of Neoadjuvant Chemoradiotherapy for Rectal Cancer	NCT04970498	Rectal Cancer S... Rectal Cancer S...	MRI blood routine t...	-	Peking University Third Hospital
TNT to Increase the Clinical Complete Response Rate for Distal LARC	NCT03840239	Rectal Cancer Rectal Cancer S... Rectal Cancer S... Chemoradiation	Capecitabine, O... External beam r... Surgery Watch and wait ...	18 Years - 70 Years	Sun Yat-sen University

Spots Global Cancer Trial Database for rectal cancer stage ii